Microbes and health: Nov 6 Flashcards
(25 cards)
what is vibrio cholerae? who investigated the source of the diesease
- hon snow - father of epidemiology was the first to investiagte the source
- Gram engative slightly curved bacterium
- faculative anaerobe
- highly motile by a single polar flegella
- short generation live
- lives in salt and fresh water - concentrates in shellfish and plankton
V. cholerae phylum and family
Phylum: proteobacteria (related to E.coli)
Family: vibrionaceae
What are the virulence ocmpoennt of V. cholerae? what ones are toxingenic
- O-antigen is virulence component
- O1 and O139 are toxinogenic
*O1 has given rise to pandemic strains ‘classical’ and ‘EI Tor’
- Cholera toxin (CTX) is V. cholerae’s major virulence determinant
what are the symptoms of cholera?
- begins only a few hours after infection
- sudden onset of watery explosive diarrhea
- apinful abdonimal cramping soon starts and diarrhea continues
~20 L of fluid may be lost/day -> Rice water stools teeming with bacteria
- wihtout fluid/electrolyte replacement death can occur within a few hours
*acute renal failure, severe electrolyte imbalances, coma
- With electrolyte re-hydration treatment disease is self-limiting
*NOT antibiotics
assocaited of cholerae and pandemics
deadly disease that has spread throughout world in 7 major pandemics
- notable recent outbreak oct 2010-jan 2012 in Haiti following earthquake
- epidemics usually occur in times of car and famine: people live close together in unhygienic conditions, poor/no sanitation
*cholera toxin CTX is the major virulence determinant
describe cholera toxin
A-B type toxin, Ab5 similar to E. coli Stx
- 1A subunit (active) and 5B subunits (binding) it bidns to intestinal epithelial cells
- AB5 is an ADP ribosylating toxin
- subunits are assembled in the abcterial periplasm and secreted/pumped into extracellular space - mechanism is analogous to a piston
**Bacteria itself which produces the toxin, the pump pushes toxin into host - Binds and infect intestinal epithelial cells
- Whole CTX toxin complex (5B subunits plis 1A subunit) is secreted
- the ctx genes are encoded on a lysogenic bacteriophage (CTX Φ)
*only CTX Φ V. cholerae lysogens cause cholera
cholera toxin mode of action
- 5b and 1A complex binds to ganglioside GM1 on host membrane lipid rafts
- Toxin is endocytosed
- Phagosome containgin toxin taken to ER
- A1 subunit removed from B subunits and exported into cytoplasm
- A1 petide attaches an ADP ribose to an amino acid within the host G protein that regualtes adenylate cyclase
- Cyclic AMP levels rise and activate ion transport system causing an electrolyte imbalance - water from the cell follows the ions causing diahhrea
*cAMP path has been stim and activated and causes diarrhea
what are some factors tht contributes to poorer outcomes in those with disease?
Achlorhydria - absense of HCl in digestive stomach juices (bacteria can surivve and be passed on the the GI tract
- Blood type O
- chronic medical conditions
- lack os access to oral rehydration therapy and medical services
- infants and elgerly
describe E. coli (phyllum, family, motility, etc)
Phylum: proteobacteria
Family: enterobacteriaceae
- gram negative facultative anaerobe
- motile by use of flagella
- MOST are good citizens
- few are serious pathogens like E. coli 0157:H7 which is classified asenterohemorrhagic E. coli (EHEC)
what is the toxigenic E.coli - what toxin does it produce>
E.coli 0157:H7 produces shiga toxin
- have had outbreaks in california, in arizona with romain lettuce, walkerton ontatio
- suusaly contaminated water applied to crops or in town water supply
what are the O and H in E.coli 0157:H7
- there are >700 different antigenic types of E. coli
O = lipopolysaccharide antigen, H = flagellar antigen
- can also have K antigen (capsular)
- antigens define a serotype
what is serotyping? what is a serotype?
antigenically distinct group within a bacterial species
in ecolie is specific combinations of O (lipopolysaccharide), H (flagellar) and someitmes K (capsular) antigens define a serotype
what is a pathotype?
- term used to describe a group of strains of a single species that cause a common disease suing a common set of virulence factors
what is EHEC
Enterohemorrahagic E. coli
- Zoonoses- E. coli 0157: H7 is carried asymptomatically in ruminants (ex: cattle) and shed in feces
- can contaminate water supplies, vegetables, carcasses during slaughter
- transmission is fecal to roal
- primarily a disease of economically affluence world
* EXTREAMLY low infectious dose
- not common but ver serious and sometimes fatal 0 causes bloody diarrhoea (haemorrhagic colitis), non-bloody diarrhoea and haemolytic uremic syndrome (HUS)
what are the viruelnce determinants of EHEC
- pedestal formation (on host intenstinal epithelial cells)
- rpoduction os shiga toxin
describe shiga toxin and what is the mechansims
- AB toxin
- originally comes from a bacteriophage
- cytotoxicity is due to its virulence factor mechanism - inhibition of protein synthesis within host cells
* kidney cells are particularly senstiive to intoxication
Mechanism:
- 2 subunits: A (active) and B (binding) forming functional AB5 complex
- B subunit binds and forms a pentamer in host cell membranes - formed a pore for entry of A subunit
- A subunit is one with toxic activatiy
why does EHEC cause disease in ruminants
- toxin is anbsent, fdoesnt ahve a receptor to bind
- cattle are asymptomatic reservoirs
how does EHEC cause attaching/effacing lesions?
- abcteria attaches to intestinal epithelial cells - cells have villi
- adherance causes villi at site of attachment to shrink and efface
- observe pedestals with EHEC and surrounding ‘attaching/effacing’ or ‘E/A’ lesions
what is TIR
- in EHEC
- one of many effectors that are injected into the host cell
- effectors are the mediators for communication betweent he host and bacterium
what is mycobacterium tuberculosis
- huamsna re the only reservoir
- gram positive, slow browing bacillus (takes 3 weeks for oclonies to appear)
- non motile
- acid-fast staining bacillus (way to daignose)
- has a lipid rich very thick wall with resistance to antimicrobials and impedes uptake of antibiotics
- resistant to killing by macrophages (hard to engulf)
-
what do chest X rays of TB patients show
- calcified tubercles in the lung called ghon complexes
- Can disseminate body wide through the bloodstream causing disseminated or miliary disease
*TB has a high motality rate due to multidrug resistant strains and hihg susceptibility of HIV (with low CD4+ T-cell) patient
How is tuberculosis transmitted?
- via aerosol transmission frmo people with active TB
- in latent TB the bacteria are dormant within granulomas
- TB binds and invades peritonal macrophages to inhibt phagosome-lysozome fusion & replicate in vaculoes
- induced an anti-inflammatory cytokine
*infected cells are walled off in granulomas/tubercles
what happend when infected cells are walled off in granulomas/tubercles
- layers of T cells, macrophages surround infected cells
- the center contains dead cells, live bacteria in a lipid-rich anaerobic environment
- bacteria become letent/dormant and can survive for decades
- new supplied of T-cells maintain tubercles intact in a healthy host
*reactivation of latent disease occurs when cost are immunocompromised (like HIV infection, age or other infections)
steps to TB ifnection
- If droplet contains tubercle bacilli and is inhaled it will enter the lungs and travel to alveoli
- Tubercle bacilli multiple in the alveoli
- Immune cells form a barrier shell around the tubercle bacilli called a granuloma
- Granuloma shell breaks down and the tubercle bacilli escape and rapidly multiply forming more tubercles
