toxins and anaerobes Flashcards
properties of a successful pathogen
gains access into the host
colonize tissue
resist immune system
damage host thru invasiveness and toxigenicity
anaerobic bacteria
lots of species that exist on mucosal surfaces
few are pathogenic
infections are mixed opportunistic, including either/both aerobes and anaerobes
they are sensitive to o2 intermediates:
they dont have a lot of superoxidase dismutase to remove O2 radicals and they dont have lots of catalase to remove H2O2
and they lack cytochromes-> metabolism is all fermentation
Anaerobic gram negative pathogens
sites of infections: colon, mouth, skin
infections are foul smelling due to SCFA production in fermentation
gas producing (fermentation)
poly-microbial infections (multi bacatria cause the toxin)
infections ofted due to normal gut flora
use culture techniques to isolate anaerobic pathogens
Void of aerobic bacteria (anoxic environment)
common gram- anaerobic pathogens
*bacteriodes fragilis (most intra-ab infections), common in bowel
Virulence factors: polysaccharode capsule (antiphagocytic)
aerotolerant anaerobes able to tolerate atmospheric concentrations of oxygen
encode 2 major oxidative stress response genes: cltalase and superoxidase dismutase
often isolated in mixed bacterial infection with other anaerobes, and facultative anaerobes (Peptostreptococcus)
bacteriodes fragilils is most common intra abdominal infection, the types of pathogens isolated in other surgical sites differ
sites of infection are pathogen specific, and mixed infections are common
clostridia
Anaerobic gram postive spore forming bacilli; obligate anaerobes or aerotolterant
pathogenisis: invasiveness or an exotoxin
Physiology: either saccharolytic (sugars) or proterolytic (AA
Clostridia soil inhabitants or inhabitants of intestinal tract
Invasive clostridia: histotoxic (C. Pertringens)
Toxin producing clostridia: (GI: C. difficile wproducing toxin A and B) (tetanus: C. tetani prod.: tetanus toxin) (botuslism, food poison: C. bolulinum)
histotoxin clostridia
invasive and and cause extensive destruction of muscle and connective tissue, characterized by formation of gas
Invasive C. Perfringens (alphatoxin)
cause most clostridial-mediated myonecrosis
Pathology: a deep mound to muscle predisposes infection
Steps:
1. Reduction of tissue redox potential (host cell death) pyruvate-> lactate and acid
2. Host proteases: release nutrients so clostridia can grow
3. C. perfringens-> alpha toxin (phospholipase)-> tissue damage
gas gangrene: treatment antibiotics and often amputation
general properties of bacterial toxins
Each bacterial toxin has a catalytic component (enzyme) and host cell binding component
Catalytic component (enzyme) modifies specific host macromolecules (post-translational modification)
Host cell binding component (can be tissue- specific or non-specific)
Modification are specific for each toxin:
- Diptheria toxin and Pseudomonas aeruginosa exotoxin A (ADP-ribosylate EF2: inhibits protein syntesis)
- Botulinum toxin and tetanus toxin (Protease for SNARE proteins: inhibits neurotransmittor vesicle fusion to the cell membrane)
- Large Clostridium dificile toxins (Glucosylate Rho proteins: inhibits cell motility and ultrastructure, via active modification)
- shiga toxin: Deadenlyates a adenine on RNA: inhibits protein synthesis
prevention of bacterial diseases by vaccination with toxoids of protein toxins (chemically inactivated toxin)
Dt/TT vaccine: formalin inactivated diptheria/tetanus toxins
Conjugate vaccines: Hib poly saccharide conjugated to diptheria toxoid, making a T cell-dependent immune response (IgM->IgG and memory)
Antibiotic associated diarrhea (gastrointestinal colitis)
causitive agents: C. difficile. : Toxins A and B
Antibiotic therapies may be associated with C. difficile infections where the normal floral are reduced allowing endogenous and ingested C. dificile to expand and produce Toxin A and B which contribute to diarrhea and inflammation
C. difficile infection range: asymptomatic to recurrent and life threatening
Pathology: c diff produces Toxin A&B with glucosylate Rho GTPases elicit:; Toxin A and B
actin depolymerization->disrupt gut epithelium->diarrhea
highly toxic strain of C. difficile thats resistant to fluoroquinolones
Clostridia that produce neurotoxins
C. Tetani and C. botulinum- toxin-mediated
opposite disease- tetanus and botulism
C. botulinum: flaccid paralysis, no vaccine
C. tetani: spastic paralysis (lock jaw) w/ licensed vaccine
Clostridial neurotoxins
most toxic protein toxins for humasn
moderate size with a A(catalytic) and a B (binding) structure-function
Botox:seven serotypes A-G
Tetanus toxin: single serum
Mechanism of action: Clostridium neurotoxins are proteases that cleave SNARE proteins and inhibit synaptic vesicle fusion
BoNT and TeNT cause the same thing
cellular basis for BoNT and TeNT (botox and tetanus)
BoNT remains in periphery (synaptic vesicles)- flaccid parlysis
TeNT (retrograde trafics to CNS)- spastic paralysis
Tatnus C. Tetani
Physio: Anaerobe, proteoplytic (peptides and AA)
Tetanus
Determinants of Pathogenicity: C. tetani is not invasive, remains at site of infection, but produces tetanus toxin
Intoxication: Following injury with a mixed bacterial infection, soil bacteria ferment to reduce redox potential allows for limited growth-> toxin production
prevention with formalin produces toxoid
