22. Parasites Flashcards
Parasitic protozoa are …
- pathogenic microbial eukaryotes
- protists
Define ‘symbiosis’
- association between organisms from different species
- diff types of association can be defined with 3 main categories - mutualism, commensalism and parasitism
Define ‘mutualism’
- both partners benefit from the interaction and they are co-dependent or thriving
Define ‘commensalism’
- one partner benefits from interaction
- the other is neither harmed nor benefitted
Define ‘parasitism’
- one partner relies on host for nutrients and shelter
- there is potential cost to the host - potential pathogen causing pathologies
Most parasitic protozoa are … meaning
Some are … - they don’t cause …
- obligate symbionts, they require a host to complete life cycle
- facultative pathogens - disease all the time - blurs distinction between parasites, commensals and mutualists
Define ‘opportunistic pathogens’
- those that cause pathologies when host is compromised
- e.g due to immunodeficiency - as in HIV-AIDS due to malnutrition and chemotherapies
The outcomes of a host-parasite interaction depends on …
- characteristics from all interacting partners and environments
- importance of context of interactions like oral microbiota
Adaptations of parasites to host
- highly adapted to one or more body sites of host to progress through life cycle
- best adapted parasites are least pathogenic - don’t kill host
- many parasite-host relationships are long-term, chronic, highly intimate - evidence for commensalic and mutualistic relationships
Explain monoxenous and heteroxenous parasites
- some parasites require a single host for completing life cycle - called monoxenous like Trichomonas tenax
- ones needing 2 or more are heteroxenous defining intermediate hosts as those needed for development and definite hosts where sexual maturity is reached
What is a promiscuous parasite?
- they are capable of infecting a broad range of hosts
- e.g Trichomonas tenax
Define ‘zoonoses’
- human diseases caused by animal parasites
- animal hosts represent resevoirs for human pathogens
Mucosal surfaces mediate simultaneously 2 contradictory functions. What are they?
- protect individual from microbial, chemical and physical insult
- facilitate exchanges between outside and inside the body
How do microbiota link to mucosal surface function?
- members of microbiota are intimately associated with both of the mucosal surface functions at respiratory, digestive and urogential tracts
- oral mucosa only mediate protective functions however
Define ‘eubiosis’
- microbiota taxonomic and functional configurations
- that lead to homeostasis/promote health
Define ‘dysbiosis’
- abnormal microbiota taxonomic and functional configurations
- lead to pathologies - even in absence of overt pathogens - concept of pathobionts
Define ‘pathobionts’
- members of microbiota that have potential to cause damage/pathologies
- context dependent
Some mucosal microbial parasites are considered … rather than overt pathogens
pathobionts
What archaea involved in oral microbiota?
- methanobrevibacter oralis-like
Bacteria involved in oral microbiota?
- responsible for oral disease
- for caries, periodontitis, microbial eukaryotes
- some oral bacteria can infect other body sites
Microbial eukaryotes involved in oral microbiota?
- fungi (occasional infections, Candida spp.)
- protists-protozoa-microbial parasites - members of microbiota, pathobionts (T. tenax, E. histolytica)
Define ‘autochthonous microbiota’
- micro-organisms characteristically found at particularly site
- adapted to survive and grow at given site
- two common examples is Trichomonas tenax and Entamoeba gingivalis
Define ‘allochthonous microbiota’
- micro-organisms transiently present at given site
- organisms not specific to site but colonise transiently or if site is compromised in injury/immunodeficiency e.g AIDS
- Leishmania species for example at oral-skin interface
2 fundamental issues in periodontitis
- bacteria undoubtedly principal cause of gingivitis but host response to bacteria dictates disease progress
- overwhelming evidence demonstrates it’s uncontrolled host inflammatory/immune response that largely drive tissue destruction
Key questions about periodontitis
- what drives localised/contained inflammatory response to gingivitis to progressive, destructive periodontitis?
- is bacterial invasion of tissues an initiator or consequence of disease?
- is it a spontaneous evolution of maturing biofilms or is it driven by changing environment mediated by host response?
Explain cutaneous leishmaniasis
- most common form
- causes skin legions mainly ulcers
- life-long scars left and serious disability/stigma
- over 95% of new CL cases occur in 6 countries - Afghanistan, Algeria, Brazil, Columbia, Iran, Iraq and Syria
- estimated around 600,00 to 1 million new cases appear worldwide annually
Explain visceral leishmaniasis
- aka kala-azar
- fatal if untreated in over 95% of cases
- irregular bouts of fever, weight loss, enlargement of spleen and anaemia
- most cases in Brazil, East Africa and South-East Asia. 50,000 to 90,000 new cases worldwide a year (lots in Sudan, South Sudan, Nepal, Somalia, Brazil, China)
Explain mucocutaneous leishmaniasis
- leads to partial or total destruction of mucous membranes of nose, mouth, throat
- over 90% of mucocutaneous leishmaniasis occur in Bolivia, Brazil, Ethiopia and Peru
2 common microbial eukaryotes associated with periodontitis
- Trichomonas tenax
- Entamoeba gingivalis
Roles of Trichomonas vaginalis
- infects humans
- genitourinary tract
- associated with HIV, bacterial vaginosis, pelvic inflammatory disease and low birth weight
Role of Trichomonas gallinae
- infects birds
- common in pigeons and columbiform
- causes epidemics and high mortality rates
Role of Trichomonas tenax
- infects humans, dogs and cats
- oral cavity, upper GI tract and lungs
- associated with periodontis (35% PP)
- identified in uretha of MSM
Trichomonas species can be isolated in …
humans and birds
Phylogeny supports a … origin of Trichomonas species
zoonotic
Explain T. tenax in human patients
- more frequent associated with severe periodontitis
- 2 genotypes (among 3) were significantly associated with it
- T. tenax appears to be associated with onset/evolution of periodontal diseases
- cause or consequence of disease can’t be established
What Trichomonads are present in the gut?
- various
- Dientamoeba fragilis
- Pentatrichomonas hominis
What Trichomonads are present in the lung?
- various
- AIDS
- ARDS
- CF patients
What Trichomonads are present in the mouth?
- tenax
- associated with periodontitis
What Trichomonads are present in the UGT?
- Trichomonas vaginalis
What Trichomonads are present in the skin?
none
Pathobiology of Trichomonas vaginalis
- T. vaginalis endosymbionts
- with TVV - totoviruses
- incites inflammation in host immunity
What is the molecular basis of Trichomonas spp. mucosal life style and pathology?
- cell surface proteins involved in parasite-microbiota/host interactions
- metabolic enzymes
- enzymes targeting other microbes
- shared and transcribed genes among trichomonas spp. are prioritised for functional characterisation
What are BspA proteins?
- expressed on cell surface of 2 oral bacterial pathogens (Tannerella forsythensis/bacteroidetes and Treponema denticola/spirochetes)
- adhesins mediating binding to epithelial cells and ECM proteins and cell-cell interactions between Tannerella and Treponema
- mediate invasion of epithelial cells and trigger innate immune and antibody responses
What could be the function of BspA proteins in Trichomonas tenax?
- induce inflammation (?)
- binding to human cells/proteins?
- mediate binding to oral bacteria-phagocytosis?
What are candidate peptidoglycan targeting enzymes?
- NlpC/P60, GH19, GH25
- shared genes across all 3 trichomonas species
- could target members of microbiota present in various species and mucosa
- can explain capacity to thrive on various mucosal surfaces (oral, upper digestive tract and urogenital tract) across different species (pigeon, pet animals, human)
- can contribute at facilitating zoonotic transfers
Define peptidoglycan fragments as important inducers of inflammation?
- relative stimulatory potency of pnuemococcal wall components
- exposed to human peripheral blood mononuclear cells (lymphocytes, monocytes, natural killer cells, dendritic cells)
Pathway for peptidoglycan fragments causing inflammation
- PNG fragments stimulate broad specificity inflammatory responses recruiting and activating phagocytes
- PNG as pathogen-associated molecular patterns (PAMP)
- PAMP consist of molecules not found in host, including bacterial cell wall components like PGN
- recognition of PAMPs is mediated by specific proteins called pattern recognition molecules - these activate inflammatory signalling pathways and stimulation of innate immune response
Entamoeba … is the loss of cyst form, entamoeba … with cysts
- giginvalis
- histolytica
Virulence regulation of E. histolytica
- pathobiota induces inflammatory cascade, barrier dysfunction and nutrient malabsorption which increase susceptibility to E. histolytica infection
- alters host microbiota - microbiota controls host nutrient availability and absorption level, integritty of mucins - leptin production, competitive exclusion of pathogens and intestinal barrier function/ion transport
What is the causal relationship between E. gingivalis and periodontitis?
- work shows parasites detected by microscope mainly - if not exclusively - belong to species E. gingivalis and presence of parasite correlates with periodontitis
Explain the potential causal link between T. tenax and/or E.gingivalis and periodontitis
- could induce and/or worsen the dysbiotic state of microbial community
- could be accesory pathogens
- could be keystone pathogens and initiate damaging inflammation or contribute to worsening inflammatory tone
- could do all of the above
- could alternatively benefit from dysbiosis or inflammation to thrive - bystanders
It is important to understand the spatial and temporal sequence of events in periodontitis and pocket formation because …
- inflammation always precedes periodontal pathogen overgrowth
- thus seems most probable that host response not microbes that determine eventual outcome of host parasite interactions with periodontal pockets
