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Many protists exist as parasites that infect and cause diseases in their hosts.
- Identify the effects on humans of protist pathogens
- The protist parasite Plasmodium must colonize both a mosquito and a vertebrate; P. falciparum, which is responsible for 50 percent of malaria cases, is transmitted to humans by the African malaria mosquito, Anopheles gambiae.
- When P. falciparum infects and destroys red blood cells, they burst, and parasitic waste leaks into the blood stream, causing deliruim, fever, and anemia in patients.
- Trypanosoma brucei is responsible for African sleeping sickness which the human immune system is unable to guard against since it has thousands of possible antigens and changes surface glycoproteins with each infectious cycle.
- Another Trypanosoma species, T. cruzi, inhabits the heart and digestive system tissues, causing malnutrition and heart failure.
- Trypanosoma: infects a variety of hosts and cause various diseases, including the fatal African sleeping sickness in humans
- plasmodium: parasitic protozoa that must colonize a mosquito and a vertebrate to complete its life cycle
- pathogen: any organism or substance, especially a microorganism, capable of causing disease, such as bacteria, viruses, protozoa, or fungi
A pathogen is anything that causes disease. Parasites live in or on an organism and harm that organism. A significant number of protists are pathogenic parasites that must infect other organisms to survive and propagate. Protist parasites include the causative agents of malaria, African sleeping sickness, and waterborne gastroenteritis in humans.
Members of the genus Plasmodium must colonize both a mosquito and a vertebrate to complete their life cycle. In vertebrates, the parasite develops in liver cells and goes on to infect red blood cells, bursting from and destroying the blood cells with each asexual replication cycle. Of the four Plasmodium species known to infect humans, P. falciparum accounts for 50 percent of all malaria cases and is the primary cause of disease-related fatalities in tropical regions of the world. In 2010, it was estimated that malaria caused between one and one-half million deaths, mostly in African children. During the course of malaria, P. falciparum can infect and destroy more than one-half of a human’s circulating blood cells, leading to severe anemia. In response to waste products released as the parasites burst from infected blood cells, the host immune system mounts a massive inflammatory response with episodes of delirium-inducing fever as parasites lyse red blood cells, spilling parasitic waste into the bloodstream. P. falciparum is transmitted to humans by the African malaria mosquito, Anopheles gambiae. Techniques to kill, sterilize, or avoid exposure to this highly-aggressive mosquito species are crucial to malaria control.
Red blood cells are shown to be infected with P. falciparum, the causative agent of malaria. In this light microscopic image taken using a 100× oil immersion lens, the ring-shaped P. falciparumstains purple.
Trypanosoma brucei, the parasite that is responsible for African sleeping sickness, confounds the human immune system by changing its thick layer of surface glycoproteins with each infectious cycle. The glycoproteins are identified by the immune system as foreign antigens and a specific antibody defense is mounted against the parasite. However, T. brucei has thousands of possible antigens; with each subsequent generation, the protist switches to a glycoprotein coating of a different molecular structure. In this way, T. brucei is capable of replicating continuously without the immune system ever succeeding in clearing the parasite. Without treatment, T. brucei attacks red blood cells, causing the patient to lapse into a coma and eventually die. During epidemic periods, mortality from the disease can be high. Greater surveillance and control measures lead to a reduction in reported cases; some of the lowest numbers reported in 50 years (fewer than 10,000 cases in all of sub-Saharan Africa) have happened since 2009.
In Latin America, another species, T. cruzi, is responsible for Chagas disease. T. cruzi infections are mainly caused by a blood-sucking bug. The parasite inhabits heart and digestive system tissues in the chronic phase of infection, leading to malnutrition and heart failure due to abnormal heart rhythms. An estimated 10 million people are infected with Chagas disease; it caused 10,000 deaths in 2008.
Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts by Legionella pneumophila
Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped with more sophisticated innate defence mechanisms than are protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defence processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (
80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in protist biology, that are modulated by L. pneumophila, including TLR2 signalling, NF-κB, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC-Naip5 inflammasomes. Importantly, L. pneumophila infects haemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although coevolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of coevolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.
Keywords: Legionella ecology immunology infection mechanism of action microbial-cell interaction.
© 2018 John Wiley & Sons Ltd.
Manipulation of evolutionarily conserved and…
Manipulation of evolutionarily conserved and metazoan-specific innate defense processes by L. pneumophila .…
Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis
Background: Small non-coding RNAs play critical regulatory roles in post-transcription. However, their characteristics in Trichomonas vaginalis, the causative agent of human sexually transmitted trichomoniasis, still remain to be determined.
Methods: Small RNA transcriptomes from Trichomonas trophozoites were deep sequenced using the Illumina NextSeq 500 system and comprehensively analyzed to identify Trichomonas microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs). The tsRNA candidates were confirmed by stem-loop quantitative reverse transcription-PCR, and motifs to guide the cleavage of tsRNAs were predicted using the GLAM2 algorithm.
Results: The miRNAs were found to be present in T. vaginalis but at an extremely low abundance (0.0046%). Three categories of endogenous Trichomonas tsRNAs were identified, namely 5'tritsRNAs, mid-tritsRNAs and 3'tritsRNAs, with the 5'tritsRNAs constituting the dominant category (67.63%) of tsRNAs. Interestingly, the cleavage site analysis verified both conventional classes of tRNA-derived fragments (tRFs) and tRNA-halves in tritsRNAs, indicating the expression of tRNA-halves in the non-stress condition. A total of 25 tritsRNAs were experimentally confirmed, accounting for 78.1% of all tested candidates. Three motifs were predicted to guide the production of tritsRNAs. The results prove the expression of tRFs and tRNA-halves in the T. vaginalis transcriptome.
Conclusions: This is the first report of genome-wide investigation of small RNAs, particularly tsRNAs and miRNAs, from Trichomonas parasites. Our findings demonstrate the expression profile of tsRNAs in T. vaginalis, while miRNA was barely detected. These results may promote further research aimed at gaining a better understanding of the evolution of small non-coding RNA in T. vaginalis and their functions in the pathogenesis of trichomoniasis.
Keywords: Transfer RNA Trichomonas vaginalis Trichomoniasis tRFs tRNA-derived small RNAs tRNA-halves.
Free-living amoebae and squatters in the wild: ecological and molecular features
Free-living amoebae are protists frequently found in water and soils. They feed on other microorganisms, mainly bacteria, and digest them through phagocytosis. It is accepted that these amoebae play an important role in the microbial ecology of these environments. There is a renewed interest for the free-living amoebae since the discovery of pathogenic bacteria that can resist phagocytosis and of giant viruses, underlying that amoebae might play a role in the evolution of other microorganisms, including several human pathogens. Recent advances, using molecular methods, allow to bring together new information about free-living amoebae. This review aims to provide a comprehensive overview of the newly gathered insights into (1) the free-living amoeba diversity, assessed with molecular tools, (2) the gene functions described to decipher the biology of the amoebae and (3) their interactions with other microorganisms in the environment.
Keywords: environment gene function microbial diversity protist symbiosis.
Microbes known as protists are understudied, but their impact on ecosystems could be huge
Among the large cast of microbiome players, bacteria have long been hogging the spotlight. But the single-celled organisms known as protists are finally getting the starring role they deserve.
A group of scientists who study the interactions between plants and microbes have released a new study detailing the dynamic relationships between soil-dwelling protists and developing plants, demonstrating that soil protists respond to plant signals much like bacteria do.
An enormous variety and diversity of microbes live in soil, and studying how these organisms interact with each other and with plant roots is a hot topic in biology, as it has applications for agriculture, land stewardship, and climate change resilience technologies.
"Protists represent a new frontier in the study of soil microbial ecology," said lead author Javier A. Ceja Navarro, a research scientist at Lawrence Berkeley National Laboratory (Berkeley Lab). "Here we show that this group of organisms really must be included in microbial studies aiming to understand how microbes interact with plants."
Protists are not a distinct lineage of organisms, but rather a category assigned to any single-celled eukaryotic organism (an organism whose cells contain a nucleus) that is not a plant, fungi, or animal. This diverse group of 200,000+ species (new ones are being discovered continuously) includes amoebas, diatoms, dinoflagellates, slime molds, and even various parasites -- such as the malaria-causing Plasmodium and the eponymous Giardia-causing genus of protozoans.
Protists are found across the planet in a variety of ecosystems. Some species, like certain marine plankton protists and human disease-causing protists have been studied closely. Yet for the majority of species, scientists are just beginning to scratch the surface of what the organism does and how they respond to the environment. Such is the case for soil protists.
According to Navarro, protists are known to control soil microbial dynamics and nutrient cycling by feeding on other microbes. Although there is a good body of knowledge about their interactions with other members of the soil microbiome, little is known about how protists respond to changes in their environment.
"Even though protists are important and their relevance has been known for decades, our study is the first one showing an association of protists with plants in a large-scale field experiment," noted project leader Mary Firestone, a faculty scientist in Berkeley Lab's Earth and Environmental Sciences Area and a professor at UC Berkeley. The project was a collaboration among scientists from Berkeley Lab, UC Berkeley, Lawrence Livermore National Laboratory (LLNL), the Noble Research Institute, and the University of Oklahoma.
The team grew switchgrass -- a crop proposed for large-scale biofuel production -- from seedlings at two large-scale field sites, and took samples of the soil surrounding the roots of plants at different stages of growth. They used next-generation genome sequencing to identify the types of protists present in each sample and the abundance of each species.
"As plants grow, the cells in their roots release metabolites that send signals out to the surrounding soil environment," added Jennifer Pett-Ridge, a senior staff scientist from LLNL. "We saw that protists communities shift and change in response to the plant's effects -- in a manner that is similar to what we've observed for bacterial communities."
"Future studies focusing on understanding the mechanisms of plant establishment in soil will need to consider protists as a key part of the plant microbiome," added Navarro, who is part of Berkeley Lab's Biosciences Area. "Ignoring protists in terrestrial ecological studies will result in a big knowledge gap that will make our understanding of the environmental microbiome incomplete."
23.4 Ecology of Protists
By the end of this section, you will be able to do the following:
- Describe the role that protists play in the ecosystem
- Describe important pathogenic species of protists
Protists function in various ecological niches. Whereas some protist species are essential components of the food chain and generators of biomass, others function in the decomposition of organic materials. Still other protists are dangerous human pathogens or causative agents of devastating plant diseases.
Primary Producers/Food Sources
Protists are essential sources of food and provide nutrition for many other organisms. In some cases, as with zooplankton, protists are consumed directly. Alternatively, photosynthetic protists serve as producers of nutrition for other organisms. Paramecium bursaria and several other species of ciliates are mixotrophic due to a symbiotic relationship with green algae. This is a temporary version of the secondarily endosymbiotic chloroplast found in Euglena. But these symbiotic associations are not restricted to protists. For instance, photosynthetic dinoflagellates called zooxanthellae provide nutrients for the coral polyps (Figure 23.32) that house them, giving corals a boost of energy to secrete their calcium carbonate skeleton. In turn, the corals provide the protist with a protected environment and the compounds needed for photosynthesis. This type of symbiotic relationship is important in nutrient-poor environments. Without dinoflagellate symbionts, corals lose algal pigments in a process called coral bleaching, and they eventually die. This explains why reef-building corals typically do not reside in waters deeper than 20 meters: insufficient light reaches those depths for dinoflagellates to photosynthesize.
The protists and their products of photosynthesis are essential—directly or indirectly—to the survival of organisms ranging from bacteria to mammals (Figure 23.33). As primary producers, protists feed a large proportion of the world’s aquatic species. (On land, terrestrial plants serve as primary producers.) In fact, approximately 25 percent of the world’s photosynthesis is conducted by photosynthetic protists, particularly dinoflagellates, diatoms, and multicellular algae.
Protists do not create food sources only for sea-dwelling organisms. Recall that certain anaerobic parabasalid species exist in the digestive tracts of termites and wood-eating cockroaches, where they contribute an essential step in the digestion of cellulose ingested by these insects as they consume wood.
As we have seen, a pathogen is anything that causes disease. Parasitic organisms live in or on a host organism and harm the organism. A small number of protists are serious pathogenic parasites that must infect other organisms to survive and propagate. For example, protist parasites include the causative agents of malaria, African sleeping sickness, amoebic encephalitis, and waterborne gastroenteritis in humans. Other protist pathogens prey on plants, effecting massive destruction of food crops.
In 2015 WHO reported over 200 million cases of malaria, mostly in Africa, South America, and southern Asia. However, it is not well known that malaria was also a prevalent and debilitating disease of the North Central region of the United States, particularly Michigan, with its thousands of lakes and numerous swamps. Prior to the civil war, and the drainage of many swamps, virtually everyone who immigrated to Michigan picked up malaria (ague as it was called in the late 1800s), and the pale, sallow, bloated faces of that period were the rule. The only healthy faces were worn by those immigrants who had just arrived. In fact, there were more deaths due to malaria in Michigan than those from the Civil War.
We now know that malaria is caused by several species of the apicomplexan protist genus Plasmodium. Members of Plasmodium must sequentially require both a mosquito and a vertebrate to complete their life cycle. In vertebrates, the parasite develops in liver cells (the exoerythrocytic stage) and goes on to infect red blood cells (the erythrocytic stage), bursting from and destroying the blood cells with each asexual replication cycle (Figure 23.34). Of the four Plasmodium species known to infect humans, P. falciparum accounts for 50 percent of all malaria cases and is the primary (and deadliest) cause of disease-related fatalities in tropical regions of the world. In 2015, it was estimated that malaria caused over 400,000 deaths, mostly in African children. During the course of malaria, P. falciparum can infect and destroy more than one-half of a human’s circulating blood cells, leading to severe anemia. In response to waste products released as the parasites burst from infected blood cells, the host immune system mounts a massive inflammatory response with episodes of delirium-inducing fever (paroxysms) as parasites lyse red blood cells, spilling parasite waste into the bloodstream. P. falciparum is transmitted to humans by the African mosquito, Anopheles gambiae. Techniques to kill, sterilize, or avoid exposure to this highly aggressive mosquito species are crucial to malaria control. Ironically, a type of genetic control has arisen in parts of the world where malaria is endemic. Possession of one copy of the HbS beta globin allele results in malaria resistance. Unfortunately, this allele also has an unfortunate second effect when homozygous it causes sickle cell disease.
Link to Learning
This movie depicts the pathogenesis of Plasmodium falciparum, the causative agent of malaria.
Trypanosoma brucei (Figure 23.35), transmitted by tsetse flies (Glossina spp) in Africa, and related flies in South America, is an flagellated endoparasite responsible for the deadly disease nagana in cattle and horses, and for African sleeping sickness in humans. This trypanosome confounds the human immune system by changing its thick layer of surface glycoproteins with each infectious cycle. (The glycoproteins are identified by the immune system as foreign antigens, and a specific antibody defense is mounted against the parasite.) However, T. brucei has thousands of possible antigens, and with each subsequent generation, the protist switches to a glycoprotein coating with a different molecular structure. In this way, T. brucei is capable of replicating continuously without the immune system ever succeeding in clearing the parasite. Without treatment, T. brucei attacks red blood cells, causing the patient to lapse into a coma and eventually die. During epidemic periods, mortality from the disease can be high. Greater surveillance and control measures lead to a reduction in reported cases some of the lowest numbers reported in 50 years (fewer than 10,000 cases in all of sub-Saharan Africa) have happened since 2009.
Link to Learning
This movie discusses the pathogenesis of Trypanosoma brucei, the causative agent of African sleeping sickness.
In Latin America, another species of trypanosome, T. cruzi, is responsible for Chagas disease. T. cruzi infections are mainly caused by a blood-sucking “kissing bug” in the genus Triatoma. These “true bugs” bite the host during the night and then defecate on the wound, transmitting the trypanosome to the victim. The victim scratches the wound, further inoculating the site with trypanosomes at the location of the bite. After about 10 weeks, individuals enter the chronic phase but most never develop further symptoms. In about 30 percent of cases, however, the trypanosome causes further damage, especially to the heart and digestive system tissues in the chronic phase of infection, leading to malnutrition and heart failure due to abnormal heart rhythms. An estimated 10 million people are infected with Chagas disease, and it caused 10,000 deaths in 2008.
Protist parasites of terrestrial plants include agents that destroy food crops. The oomycete Plasmopara viticola parasitizes grape plants, causing a disease called downy mildew (Figure 23.36). Grape plants infected with P. viticola appear stunted and have discolored, withered leaves. The spread of downy mildew nearly collapsed the French wine industry in the nineteenth century.
Phytophthora infestans is an oomycete responsible for potato late blight, which causes potato stalks and stems to decay into black slime (Figure 23.37). Widespread potato blight caused by P. infestans precipitated the well-known Irish potato famine in the nineteenth century that claimed the lives of approximately 1 million people and led to the emigration of at least 1 million more from Ireland. Late blight continues to plague potato crops in certain parts of the United States and Russia, wiping out as much as 70 percent of crops when no pesticides are applied.
The fungus-like protist saprobes are specialized to absorb nutrients from nonliving organic matter, such as dead organisms or their wastes. For instance, many types of oomycetes grow on dead animals or algae. Saprobic protists have the essential function of returning inorganic nutrients to the soil and water. This process allows for new plant growth, which in turn generates sustenance for other organisms along the food chain. Indeed, without saprobe species, such as protists, fungi, and bacteria, life would cease to exist as all organic carbon became “tied up” in dead organisms.
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Excavata are considered primitive eukaryotes. They are characterized by a feeding groove with a posteriorly located flagella, which allows them to create a current that captures small food particles.  The cytostome is the specialized structure that allows the protists this function. This supergroup Excavata includes the subgroups Diplomonads (Fornicata), Parabasalids, and Euglenozoans. 
Dipolomonads used to be defined as Fornicata, but their characteristics remain the same despite their renaming. They are microaerophilic protists. Diplomonads were previously defined by the lack of a mitochondria, but recent studies have found that they have a nonfunctional, mitochondrial remnant organelle called a mitosome. Most are harmless except for Giardia, Hexamita salmonis, and Histomonas meleagridis. Giardia causes diarrhea, Hexamita salmonis is a fish parasite, and Histomonas meleagridis is a turkey pathogen.
Giardia intestinalis is a human pathogen, which is transmitted by cyst contaminated water. It causes epidemic diarrhea from contaminated water. You can tell you may be infected by the observation of cysts or trophozoites in stools and ELISA (enzyme-linked immunosorbent assay) test. To prevent contamination, avoid any possibly contaminated water, and if contaminated water is the only thing available to drink, a slow sand filter should be used. A study found that the chlorination of water and nutritional intervention had no effect on childhood giardia infection. Only handwashing and hygienic sanitation interventions reduced infection rates in children. 
Hexamita salmonis is a common flagellated fish pathogen. Infected fish are weak, emaciated, and typically swim on their side. 
Histomonas meleagridis is a common bird pathogen that causes histomoniasis. Signs of histomoniasis include reduced appetite, drooping wings, unkempt feathers, and yellow fecal droppings. 
Most Parabasalia are flagellated endosymbionts of animals. They lack a distinct cytostome, which means they must use phagocytosis to engulf food. There are two subgroups: Trichonympha and Trichomonadida. Trichonympha are obligate mutualists of wood-eating insects such as termites. They secrete cellulase, which is used for digesting wood. The next subgroup, Trichomonadida, does not require oxygen and possesses hydrogenosomes. They only reproduce through asexual reproduction and some strains are human pathogens. There are three types of pathogenic parabasalia: Trichomonas foetus, Dientamoeba fragilis, and Trichomonas vaginalis. Trichomonas foetus causes spontaneous abortion in cattle, Dientamoeba fragilis causes diarrhea in humans, and Trichomonas vaginalis is a sexually transmitted disease. 
Trichomonas foetus is a parasite that resides in the urogenital tract of cattle and causes bovine trichomoniasis. Trichomoniasis is a sexually transmitted disease that causes infertility in heifers. Most infertility is caused by sudden embryonic death.  Various imidazoles have been used to treat infected bulls, but none are safe and effective. Ipronidazole is probably most effective but it frequently causes sterile abscesses at injection sites. 
Dientamoeba fragilis is a parasite that lives in the large intestine of humans. No one knows how D. fragilis is spread one possibility is from swallowing contaminated water or food. Many people who are infected with this parasite show no signs of being infected. Sometimes the infection can be observed the most common symptoms include diarrhea, stomach pains, loss of appetite, nausea, and fatigue. 
Trichomonas vaginalis is a sexually transmitted disease. Men who are infected rarely show any symptoms (asymptomatic). Women who are infected usually show signs of soreness, inflammation, and redness around the vagina and a possible change in vaginal discharge. Trichomonas vaginalis can be treated with a course of antibiotics. 
Most Euglenozoa are photoautotrophic, but some are chemoorganotrophs (saprophytic). They are commonly found in freshwater. The members of the phylum Euglenozoa have a pellicle for support, a red eye spot called a stigma to orient the cell toward light, chlorophyll a and b to assist in the process of photosynthesis, contractile vacuoles, and flagella.
One major pathogen from the phylum Euglenozoa is Leishmania. Leishmania causes leishmaniasis. The symptoms of leishmaniasis include systemic and skin/membrane damage. Leishmania parasites spread by phlebotomine sand flies in the tropics, subtropics, and southern Europe.  They may manifest cutaneously (cutaneous leishmaniasis) as skin sores with as scab a few weeks after the bite or internally (visceral leishmaniasis), affecting the organs, which can be life-threatening. Cutaneous leishmaniasis can spread to the mucus membranes and cause mucosal leishmaniasis even years after the initial infection.  Cutaneous leishmaniasis heals on its own and leaves bad scars.  Only FDA approved for visceral leishmaniasis is amphotericin B and oral miltefosine for cutaneous and mucosal leishmaniasis diagnosis- tissue specimen, bone marrow, blood tests detect antibody to parasite for visceral leishmaniasis.  
The second pathogen from this phylum is Trypanosoma cruzi. Trypanosoma cruzi causes Chagas disease and is transmitted by the reduviid bug, also known as the “kissing bug.” Chagas disease is diagnosed using a physical exam and blood test.  The only treatment includes antiparasitics only from the CDC, which are not FDA approved.  Acute Chagas disease has a quick onset, the trypanosomes enter the bloodstream, they become amastigotes, and replicate. Acute Chagas disease can be treated using benznidazole or nifurtimox. Chronic chagas disease is asymptomatic and causes heart and gastrointestinal cells to be affected. Currently, there are only investigational treatments for this disease. Unfortunately, vaccines are not effective with Chagas disease due to antigenic variation. This pathogen causes damage to the nervous system.
African Sleeping Sickness is caused by Trypanosoma brucei rhodensiense and Trypanosoma brucei gambiense, and is transmitted by the tsetse fly. It is diagnosed by a physical exam and blood test. African sleeping sickness causes interstitial inflammation, lethargy, brain swelling, and death within one to three years. Drug therapy, using Eflornithine and Melarsoprol Pentamidine for T. gambiense and Suramin (Antrypol) for either Trypanosoma brucei rhodensiense and Trypanosoma brucei gambiense, or combinations of these medications, can help treat this disease, but vaccines can not be used due to antigenic variation.
Amoebozoa are characterized by the use of pseudopodia for movement and feeding. These protists reproduce by binary or multiple fission.
Entamoebida lack mitochondria and possess mitosomes. Entamoeba histolytica is a pathogenic parasite known to cause amoebiasis, which is the third leading cause of parasitic deaths.  It is diagnosed by the assessment of stool samples.  Amoebiasis is caused by the ingestion of food or water contaminated with feces or other bodily wastes of an infected person, which contain cysts, the dormant form of the microbe. These cysts on reaching the terminal ileum region of the gastrointestinal tract give rise to a mass of proliferating cells, the trophozoite form of the parasite, by the process of excystation.  Symptoms of this infection include diarrhea with blood and mucus, and can alternate between constipation and remission, abdominal pain, and fever. Symptoms can progress to ameboma, fulminant colitis, toxic megacolon, colonic ulcers, leading to perforation, and abscesses in vital organs like liver, lung, and brain. Amoebiasis can be treated with the administration of anti-amoebic compounds, this often includes the use of Metronidazole, Ornidazole, Chloroquine, Secnidazole, Nitazoxanide and Tinidazole. Tinidazole may be effective in curing children.  The usage of conventional therapeutics to treat amoebiasis if often linked with substantial side effects, a threat to the efficacy of these therapeutics, further worsened by the development of drug resistance in the parasite.  Amoebic meningoencephalitis and keratitis is a brain-eating amoeba caused by free-living Naeglaria and Acanthomoeba. One way this pathogen can be acquired is by soaking contact lenses in water instead of contact solution. This will result in progressive ulceration of the cornea.  This pathogen can be diagnosed by demonstration of amoebae in clinical specimens. There is currently no drug therapy available for amoebic meningoencephalitis and keratitis.
The supergroup SAR includes Rhizaria, Alveolata, and Stramenopiles and is distinguished by fine pseudopodia which can be branched, simple, or connected.
Some members of Stramenopila are brown algae, diatoms, and water molds. An example of Stramenopila are Peronosporomycetes. The most well-known example of Peronosporomycetes is Phytophthora infestans. This organism caused the Great Famine of Ireland in the 1850s. 
Alveolata is a large group, which includes Dinoflagellata, Ciliophora, and Apicomplexa. 
Balantidium Coli (Balantidiasis) is an example of a member of the phylum Ciliophora. Balantidiasis is the only ciliate known to be capable of infecting humans, and swine are the primary reservoir host.  Balantidiasis is opportunistic and rare in Western countries.  Apicomplexans are parasites of animals and contain an arrangement of organelles called the apical complex. One example of an apicomplexan is Malaria. Five species of plasmodium cause malaria in animals. Malaria is transmitted by the bite of an infected female mosquito. Symptoms of malaria include: periodic chills and fever, anemia, and hypertrophy of the liver and spleen. Cerebral malaria can occur in children. In order to diagnose Malaria, doctors will look for parasites in Wright-or-Giemsa-stained red blood cells and serological tests. Treatment includes antimalarial drugs, however, resistance has been observed. New vaccines are being discovered to this day. Preventative measures that can be taken include sleeping with netting and using insecticide to prevent mosquitoes. Eimeria is another example of an apicomplexan pathogen. This pathogen causes cecal coccidiosis in chickens. Coccidiosis is a parasitic disease of the intestinal tract.  This disease is treated by placing anticoccidials in the chickens’ feed. It also causes malabsorption, diarrhea, and sometimes bloody diarrhea in animals. Theileria parva & T. annulata are tick-borne parasites which cause fatal East Coast fever in cattle. East Coast fever is transmitted by the bite of the three-host tick Phipicephalus appendiculatus and results in respiratory failure and death in African cattle. Most hosts of P. appendiculatus succumb to pulmonary edema and die within three weeks of infection. The severity of the infection can be lessened by treatment with antiprotozoal drugs like buparvaquone. Toxoplasma causes toxoplasmosis and can be acquired from undercooked meat or cat feces containing Toxoplasma gondii. The majority of the 60 million Americans infected with T. gondii are asymptomatic. The group most vulnerable to this pathogen are the fetuses of mothers who have been infected with the parasite for the first time during pregnancy. This can result in damage to the fetus’s brain, eyes, and other organs. Treatment is available for pregnant women and the immunosuppressed.  Cryptosporidiosis can be contracted through contact with water, food, soil, or surfaces contaminated with feces containing the Cryptosporidium. Immunocompromised people are the most susceptible. Cryptosporidiosis causes watery diarrhea and can resolve itself without medical intervention. It is diagnosed by examining stool samples, and diarrhea can be treated using Nitazoxanide. 
Plasmodiophorids and Halosporidians are two examples of parasitic Rhizaria. Plasmodiophorids cause infections in crops such as Spongospora subterranea. They cause powdery scabs and galls and disrupt growth. Halosporidians cause infections in marine invertebrates such as Mikrocytos mackini in Pacific oysters. Mikrocytos mackini are abscesses or green pustules on palps and mantles of certain molluscs. 
The supergroup Archaeplastida includes red algae, green algae and land plants. Each of these three groups have multicellular species and the green and red algae have many single-celled species. The land plants are not considered protists. 
Red algae are primarily multicellular, lack flagella, and range in size from microscopic, unicellular to large, multicellular forms. Some species of red algae contain phycoerythrins, photosynthetic accessory pigments that are red in color and outcompete the green tint of chlorophyll, making these species appear as varying shades of red. This group doesn’t include many pathogens. 
Green algae exhibit similar features to the land plants, particularly in terms of chloroplast structure. The green algae are subdivided into the chlorophytes and charophytes. It is very rare for green algae to become parasitic.
Prototheca moriformis belongs to the subdivision Chloroplastida. P. moriformis is a green algae that lacks chlorophyll and has turned to parasitism. It is found in sewage and the soil. P. moriformis causes a disease called protothecosis. This disease mainly infects cattle and dogs. Cattle can be affected by prototheca enteritis and mastitis.  Protothecosis is commonly seen in dogs it enters the body through the mouth or nose and causes infection in the intestines. Treatment with amphotericin B has been reported. 
Scientists have been researching new ways to fight protozoan infections, including targeting channels and transporters involved in the diseases  and finding the link between a persons microbiome and their ability to resist a protozoan infection 
This type of pathogen is not cellular, and is instead composed of either RNA (Ribonucleic acid), or DNA (Deoxyribonucleic acid). Pathogenic viruses infiltrate host cells and manipulate the organelles within the cell such as the Ribosomes, Golgi Apparatus, and Endoplasmic Reticulum to reproduce a multitude of times which commonly results in the death of the host cell via cellular decay. All the virus's that were contained within the lipid bilayer of the cell membrane are then released into the intercellular matrix to infect neighboring cells to continue the cycle.
The white blood cells are responsible for swallowing up the virus using a mechanism known as endocytosis within the extracellular matrix to reduce and fight the infection. The components within the white blood cell are responsible for destroying the virus and recycling it's components for the body to use.
Although the vast majority of bacteria are harmless or beneficial to one's body, a few pathogenic bacteria can cause infectious diseases. The most common bacterial disease is tuberculosis, caused by the bacterium Mycobacterium tuberculosis, which affects about 2 million people mostly in sub-Saharan Africa. Pathogenic bacteria contribute to other globally important diseases, such as pneumonia, which can be caused by bacteria such as Streptococcus and Pseudomonas, and foodborne illnesses, which can be caused by bacteria such as Shigella, Campylobacter, and Salmonella. Pathogenic bacteria also cause infections such as tetanus, typhoid fever, diphtheria, syphilis, and Hansen's disease. They typically range between 1 and 5 micrometers in length.
Fungi are a eukaryotic kingdom of microbes that are usually saprophytes, but can cause diseases in humans. Life-threatening fungal infections in humans most often occur in immunocompromised patients or vulnerable people with a weakened immune system, although fungi are common problems in the immunocompetent population as the causative agents of skin, nail, or yeast infections. Most antibiotics that function on bacterial pathogens cannot be used to treat fungal infections because fungi and their hosts both have eukaryotic cells. Most clinical fungicides belong to the azole group. The typical fungal spore size is 1-40 micrometers in length.
Other parasites Edit
Protozoans are single-celled eukaryotes that feed on microorganisms and organic tissues. Considered as "one-celled animal" as they have animal like behaviors such as motility, predation, and a lack of a cell wall. Many protozoan pathogens are considered human parasites as they cause a variety of diseases such as: malaria, amoebiasis, babesiosis, giardiasis, toxoplasmosis, cryptosporidiosis, trichomoniasis, Chagas disease, leishmaniasis, African trypanosomiasis (sleeping sickness), Acanthamoeba keratitis, and primary amoebic meningoencephalitis (naegleriasis).
Parasitic worms (Helminths) are macroparasites that can be seen by the naked eye. Worms live and feed in their living host, receiving nourishment and shelter while affecting the host's way of digesting nutrients. They also manipulate the host's immune system by secreting immunomodulatory products  which allows them to live in their host for years. Many parasitic worms are more commonly intestinal that are soil-transmitted and infect the digestive tract other parasitic worms are found in the host's blood vessels. Parasitic worms living in the host can cause weakness and even lead to many diseases. Parasitic worms can cause many diseases to both humans and animals. Helminthiasis (worm infection), Ascariasis, and enterobiasis (pinworm infection) are few that are caused by various parasitic worms.
Prions are misfolded proteins that are transmissible and can influence abnormal folding of normal proteins in the brain. They do not contain any DNA or RNA and cannot replicate other than to convert already existing normal proteins to the misfolded state. These abnormally folded proteins are found characteristically in many neurodegenerative diseases as they aggregate the central nervous system and create plaques that damages the tissue structure. This essentially creates "holes" in the tissue. It has been found that prions transmit three ways: obtained, familial, and sporadic. It has also been found that plants play the role of vector for prions. There are eight different diseases that affect mammals that are caused by prions such as scrapie, bovine spongiform encephalopathy (mad cow disease) and Feline spongiform encephalopathy (FSE). There are also ten diseases that affect humans such as, Creutzfeldt–Jakob disease (CJD).  and Fatal familial insomnia (FFI).
Animal pathogens Edit
Animal pathogens are disease-causing agents of wild and domestic animal species, at times including humans. 
Virulence (the tendency of a pathogen to cause damage to a host's fitness) evolves when that pathogen can spread from a diseased host, despite that host being very debilitated. An example is the malaria parasite, which can spread from a person near death, by hitching a ride to a healthy person on a mosquito that has bitten the diseased person. This is called horizontal transmission in contrast to vertical transmission, which tends to evolve symbiosis (after a period of high morbidity and mortality in the population) by linking the pathogen's evolutionary success to the evolutionary success of the host organism.
Transmission of pathogens occurs through many different routes, including airborne, direct or indirect contact, sexual contact, through blood, breast milk, or other body fluids, and through the fecal-oral route. One of the primary pathways by which food or water become contaminated is from the release of untreated sewage into a drinking water supply or onto cropland, with the result that people who eat or drink contaminated sources become infected. In developing countries, most sewage is discharged into the environment or on cropland even in developed countries, periodic system failures result in sanitary sewer overflows.
Eukaryome and Its Relationships with Microbiome
Eukaryotic microbes co-evolved with mammals over millions of years and are a normal component of the microbiome from an evolutionary point of view [7,11]. Many are stable, long-term colonists rather than transient invaders . The eukaryome can have strong effects on the composition and dynamics of the microbiome , likely with cascading consequences for our health. Although less numerous than bacteria, gut-dwelling eukaryotes are much bigger and they may have a disproportionate influence, similar to large animals in other ecosystems. For example, sharks on tropical reefs and wolves in Yellowstone have a profound effect on the entire ecosystem, and removal of these keystone species has wide consequences. It is worth testing whether targeted removal of eukaryotes—potential keystone components of the gut microbiome—in industrialized countries has contributed disproportionately to the diversity loss observed in the bacterial microbiome  and other negative health consequences discussed above. In summary, there are many exciting prospects for investigating potential benefits of the human eukaryome, all while keeping in mind the well-documented detrimental impact of some eukaryotic symbionts, particularly when present in large numbers and in mammalian hosts experiencing food limitation .
22.4 Bacterial Diseases in Humans
By the end of this section, you will be able to do the following:
- Identify bacterial diseases that caused historically important plagues and epidemics
- Describe the link between biofilms and foodborne diseases
- Explain how overuse of antibiotics may be creating “super bugs”
- Explain the importance of MRSA with respect to the problems of antibiotic resistance
To a prokaryote, humans may be just another housing opportunity. Unfortunately, the tenancy of some species can have harmful effects and cause disease. Bacteria or other infectious agents that cause harm to their human hosts are called pathogens . Devastating pathogen-borne diseases and plagues, both viral and bacterial in nature, have affected humans and their ancestors for millions of years. The true cause of these diseases was not understood until modern scientific thought developed, and many people thought that diseases were a “spiritual punishment.” Only within the past several centuries have people understood that staying away from afflicted persons, disposing of the corpses and personal belongings of victims of illness, and sanitation practices reduced their own chances of getting sick.
Epidemiologists study how diseases are transmitted and how they affect a population. Often, they must following the course of an epidemic —a disease that occurs in an unusually high number of individuals in a population at the same time. In contrast, a pandemic is a widespread, and usually worldwide, epidemic. An endemic disease is a disease that is always present, usually at low incidence, in a population.
Long History of Bacterial Disease
There are records about infectious diseases as far back as 3000 B.C. A number of significant pandemics caused by bacteria have been documented over several hundred years. Some of the most memorable pandemics led to the decline of cities and entire nations.
In the 21 st century, infectious diseases remain among the leading causes of death worldwide, despite advances made in medical research and treatments in recent decades. A disease spreads when the pathogen that causes it is passed from one person to another. For a pathogen to cause disease, it must be able to reproduce in the host’s body and damage the host in some way.
The Plague of Athens
In 430 B.C., the Plague of Athens killed one-quarter of the Athenian troops who were fighting in the great Peloponnesian War and weakened Athens’s dominance and power. The plague impacted people living in overcrowded Athens as well as troops aboard ships that had to return to Athens. The source of the plague may have been identified recently when researchers from the University of Athens were able to use DNA from teeth recovered from a mass grave. The scientists identified nucleotide sequences from a pathogenic bacterium, Salmonella enterica serovar Typhi (Figure 22.20), which causes typhoid fever. 3 This disease is commonly seen in overcrowded areas and has caused epidemics throughout recorded history.
From 541 to 750, the Plague of Justinian, an outbreak of what was likely bubonic plague, eliminated one-quarter to one-half of the human population in the eastern Mediterranean region. The population in Europe dropped by 50 percent during this outbreak. Astoundingly, bubonic plague would strike Europe more than once!
Bubonic plague is caused by the bacterium Yersinia pestis. One of the most devastating pandemics attributed to bubonic plague was the Black Death (1346 to 1361). It is thought to have originated in China and spread along the Silk Road, a network of land and sea trade routes, to the Mediterranean region and Europe, carried by fleas living on black rats that were always present on ships. The Black Death was probably named for the tissue necrosis (Figure 22.21c) that can be one of the symptoms. The "buboes" of bubonic plague were painfully swollen areas of lymphatic tissue. A pneumonic form of the plague, spread by the coughing and sneezing of infected individuals, spreads directly from human to human and can cause death within a week. The pneumonic form was responsible for the rapid spread of the Black Death in Europe. The Black Death reduced the world’s population from an estimated 450 million to about 350 to 375 million. Bubonic plague struck London yet again in the mid-1600s (Figure 22.21). In modern times, approximately 1,000 to 3,000 cases of plague arise globally each year, and a “sylvatic” form of plague, carried by fleas living on rodents such as prairie dogs and black footed ferrets, infects 10 to 20 people annually in the American Southwest. Although contracting bubonic plague before antibiotics meant almost certain death, the bacterium responds to several types of modern antibiotics, and mortality rates from plague are now very low.
Link to Learning
Watch a video on the modern understanding of the Black Death—bubonic plague in Europe during the 14 th century.
Migration of Diseases to New Populations
One of the negative consequences of human exploration was the accidental “biological warfare” that resulted from the transport of a pathogen into a population that had not previously been exposed to it. Over the centuries, Europeans tended to develop genetic immunity to endemic infectious diseases, but when European conquerors reached the western hemisphere, they brought with them disease-causing bacteria and viruses, which triggered epidemics that completely devastated many diverse populations of Native Americans, who had no natural resistance to many European diseases. It has been estimated that up to 90 percent of Native Americans died from infectious diseases after the arrival of Europeans, making conquest of the New World a foregone conclusion.
Emerging and Re-emerging Diseases
The distribution of a particular disease is dynamic. Changes in the environment, the pathogen, or the host population can dramatically impact the spread of a disease. According to the World Health Organization (WHO), an emerging disease (Figure 22.22) is one that has appeared in a population for the first time, or that may have existed previously but is rapidly increasing in incidence or geographic range. This definition also includes re-emerging diseases that were previously under control. Approximately 75 percent of recently emerging infectious diseases affecting humans are zoonotic diseases. Zoonoses are diseases that primarily infect animals but can be transmitted to humans some are of viral origin and some are of bacterial origin. Brucellosis is an example of a prokaryotic zoonosis that is re-emerging in some regions, and necrotizing fasciitis (commonly known as flesh-eating bacteria) has been increasing in virulence for the last 80 years for unknown reasons.
Some of the present emerging diseases are not actually new, but are diseases that were catastrophic in the past (Figure 22.23). They devastated populations and became dormant for a while, just to come back, sometimes more virulent than before, as was the case with bubonic plague. Other diseases, like tuberculosis, were never eradicated but were under control in some regions of the world until coming back, mostly in urban centers with high concentrations of immunocompromised people. WHO has identified certain diseases whose worldwide re-emergence should be monitored. Among these are three viral diseases (dengue fever, yellow fever, and zika), and three bacterial diseases (diphtheria, cholera, and bubonic plague). The war against infectious diseases has no foreseeable end.
Prokaryotes are everywhere: They readily colonize the surface of any type of material, and food is not an exception. Most of the time, prokaryotes colonize food and food-processing equipment in the form of a biofilm, as we have discussed earlier. Outbreaks of bacterial infection related to food consumption are common. A foodborne disease (commonly called “food poisoning”) is an illness resulting from the consumption the pathogenic bacteria, viruses, or other parasites that contaminate food. Although the United States has one of the safest food supplies in the world, the U.S. Centers for Disease Control and Prevention (CDC) has reported that “76 million people get sick, more than 300,000 are hospitalized, and 5,000 Americans die each year from foodborne illness.”
The characteristics of foodborne illnesses have changed over time. In the past, it was relatively common to hear about sporadic cases of botulism, the potentially fatal disease produced by a toxin from the anaerobic bacterium Clostridium botulinum. Some of the most common sources for this bacterium were non-acidic canned foods, homemade pickles, and processed meat and sausages. The can, jar, or package created a suitable anaerobic environment where Clostridium could grow. Proper sterilization and canning procedures have reduced the incidence of this disease.
While people may tend to think of foodborne illnesses as associated with animal-based foods, most cases are now linked to produce. There have been serious, produce-related outbreaks associated with raw spinach in the United States and with vegetable sprouts in Germany, and these types of outbreaks have become more common. The raw spinach outbreak in 2006 was produced by the bacterium E. coli serotype O157:H7. A serotype is a strain of bacteria that carries a set of similar antigens on its cell surface, and there are often many different serotypes of a bacterial species. Most E. coli are not particularly dangerous to humans, but serotype O157:H7 can cause bloody diarrhea and is potentially fatal.
All types of food can potentially be contaminated with bacteria. Recent outbreaks of Salmonella reported by the CDC occurred in foods as diverse as peanut butter, alfalfa sprouts, and eggs. A deadly outbreak in Germany in 2010 was caused by E. coli contamination of vegetable sprouts (Figure 22.24). The strain that caused the outbreak was found to be a new serotype not previously involved in other outbreaks, which indicates that E. coli is continuously evolving. Outbreaks of listeriosis, due to contamination of meats, raw cheeses, and frozen or fresh vegetables with Listeria monocytogenes, are becoming more frequent.
Biofilms and Disease
Recall that biofilms are microbial communities that are very difficult to destroy. They are responsible for diseases such as Legionnaires’ disease, otitis media (ear infections), and various infections in patients with cystic fibrosis. They produce dental plaque and colonize catheters, prostheses, transcutaneous and orthopedic devices, contact lenses, and internal devices such as pacemakers. They also form in open wounds and burned tissue. In healthcare environments, biofilms grow on hemodialysis machines, mechanical ventilators, shunts, and other medical equipment. In fact, 65 percent of all infections acquired in the hospital (nosocomial infections) are attributed to biofilms. Biofilms are also related to diseases contracted from food because they colonize the surfaces of vegetable leaves and meat, as well as food-processing equipment that isn’t adequately cleaned.
Biofilm infections develop gradually and may not cause immediate symptoms. They are rarely resolved by host defense mechanisms. Once an infection by a biofilm is established, it is very difficult to eradicate, because biofilms tend to be resistant to most methods used to control microbial growth, including antibiotics. The matrix that attaches the cells to a substrate and to other another protects the cells from antibiotics or drugs. In addition, since biofilms grow slowly, they are less responsive to agents that interfere with cell growth. It has been reported that biofilms can resist up to 1,000 times the antibiotic concentrations used to kill the same bacteria when they are free-living or planktonic. An antibiotic dose that large would harm the patient therefore, scientists are working on new ways to get rid of biofilms.
Antibiotics: Are We Facing a Crisis?
The word antibiotic comes from the Greek anti meaning “against” and bios meaning “life.” An antibiotic is a chemical, produced either by microbes or synthetically, that is hostile to or prevents the growth of other organisms. Today’s media often address concerns about an antibiotic crisis. Are the antibiotics that easily treated bacterial infections in the past becoming obsolete? Are there new “superbugs”—bacteria that have evolved to become more resistant to our arsenal of antibiotics? Is this the beginning of the end of antibiotics? All these questions challenge the healthcare community.
One of the main causes of antibiotic resistance in bacteria is overexposure to antibiotics. The imprudent and excessive use of antibiotics has resulted in the natural selection of resistant forms of bacteria. The antibiotic kills most of the infecting bacteria, and therefore only the resistant forms remain. These resistant forms reproduce, resulting in an increase in the proportion of resistant forms over non-resistant ones. In addition to transmission of resistance genes to progeny, lateral transfer of resistance genes on plasmids can rapidly spread these genes through a bacterial population. A major misuse of antibiotics is in patients with viral infections like colds or the flu, against which antibiotics are useless. Another problem is the excessive use of antibiotics in livestock. The routine use of antibiotics in animal feed promotes bacterial resistance as well. In the United States, 70 percent of the antibiotics produced are fed to animals. These antibiotics are given to livestock in low doses, which maximize the probability of resistance developing, and these resistant bacteria are readily transferred to humans.
Link to Learning
Watch a recent news report on the problem of routine antibiotic administration to livestock and antibiotic-resistant bacteria.
One of the Superbugs: MRSA
The imprudent use of antibiotics has paved the way for the expansion of resistant bacterial populations. For example, Staphylococcus aureus, often called “staph,” is a common bacterium that can live in the human body and is usually easily treated with antibiotics. However, a very dangerous strain, methicillin-resistant Staphylococcus aureus (MRSA) has made the news over the past few years (Figure 22.25). This strain is resistant to many commonly used antibiotics, including methicillin, amoxicillin, penicillin, and oxacillin. MRSA can cause infections of the skin, but it can also infect the bloodstream, lungs, urinary tract, or sites of injury. While MRSA infections are common among people in healthcare facilities, they have also appeared in healthy people who haven’t been hospitalized, but who live or work in tight populations (like military personnel and prisoners). Researchers have expressed concern about the way this latter source of MRSA targets a much younger population than those residing in care facilities. The Journal of the American Medical Association reported that, among MRSA-afflicted persons in healthcare facilities, the average age is 68, whereas people with “community-associated MRSA” ( CA-MRSA ) have an average age of 23. 4
In summary, the medical community is facing an antibiotic crisis. Some scientists believe that after years of being protected from bacterial infections by antibiotics, we may be returning to a time in which a simple bacterial infection could again devastate the human population. Researchers are developing new antibiotics, but it takes many years of research and clinical trials, plus financial investments in the millions of dollars, to generate an effective and approved drug.
Epidemiology is the study of the occurrence, distribution, and determinants of health and disease in a population. It is, therefore, part of public health. An epidemiologist studies the frequency and distribution of diseases within human populations and environments.
Epidemiologists collect data about a particular disease and track its spread to identify the original mode of transmission. They sometimes work in close collaboration with historians to try to understand the way a disease evolved geographically and over time, tracking the natural history of pathogens. They gather information from clinical records, patient interviews, surveillance, and any other available means. That information is used to develop strategies, such as vaccinations (Figure 22.26), and design public health policies to reduce the incidence of a disease or to prevent its spread. Epidemiologists also conduct rapid investigations in case of an outbreak to recommend immediate measures to control it.