Anaerobic Bacteria Flashcards
Infections by anaerobes are ______, _______ infections
mixed, opportunistic
What types of surfaces contain hundreds of species of anaerobes
mucosal surfaces
Why are anaerobes sensitive to O2 intermediates?
Have little superoxide dismutase to remove O2 radicals
Have low amounts of catalase to remove H2O
Often lack cytochromes
How do aerobic and anaerobic bacteria work together
The aerobic bacteria metabolize O2, making the environment favorable for anaerobes
Anaerobic gram negative pathogens: site of infections
Colon, mouth, and skin
Anaerobic infections are often _____ ______ due to short fatty acids produced during fermentations
foul smelling
What is a general product of fermentations
gas
Polymicrobial nature of anaerobic infection
Infections often due to the contamination of tissue by normal flora
Bacteriodes fragilis
most intra-abdominal infections
Common inhabitant of bowel
Bacteriodes Fragilis: virulence factor
- Polysaccharide capsule
- Bacteroides are aerotolerant anaerobes able to tolerate atmospheric concentrations of oxygen
- Bacteroides encode two major oxidative stress response genes, catalase and superoxide dismutase
B. Fragilis often in mixed infection with:
- Other anaerobes
- Facultative anaerobes (Peptostreptococcus)
Clostridia
Anaerobic Gram Positive, spore forming bacilli; obligate anerobes are aerotolerant
Clostridia
Pathogensis:
Physiology:
Pathogenesis: usually due to an exotoxin
Physiology: either - saccharolytic - sugars
- proteolytic - amino acids
Clostridia groups
Gastrointestinal disease: C. difficile
Histotoxic clostridia: C. perfringens
Tetanus: C. tetani
Botulism, food poisoning: C. botulinum
Clostiridia are ____ inhabitants or inhabitants of the ______ _____
Soil; Intestinal tract
Antibiotic-associated diarrhea
C. difficile (Toxins A and B)
- antibiotic therapies are associated with C. difficile infections where the normal flora are reduced allowing endogenous and ingested C. difficile to expand and produce Toxin A and Toxin B which contribute to diarrhea and inflammation
C. difficile pathology
Toxin A and Toxin B glucosylate Rho GTPases which causes actin depolymerization → disrupt gut epithelial cells
UDP-glucose + Rho → Rho-glucose (inactive) + UDP
C. dificile treatment
Metronidazole, vancomycin, or a subset of fluoroquinolines
Histotoxic clostridia
Invasive; C. perfringens - cause majority of clostridial-mediated myonecrosis
C. perfringens pathology:
A deep wound to muscle predisposes infection
- Reduction of tissue redox potential (host cell death)
- Host proteases: release nutrients (Clostridia grow)
- C. perfringens → alpha toxin (phospholipase) - gas gangrene
Clostridial neurotoxins
C. tetani (spastic paralysis), C. botulinum (flaccid paralysis)
Neurotoxins
150 kDa single protein with an A:B structure-function organization 7 serotypes of Botulinum toxin (BoNT) A,B,C,D,E,F and G defined antisera neutralization and tetanus toxin
Clostridium neurotoxins cleave _____ proteins and inhibit ______ _____ ______
SNARE; synaptic vesicle fusion
BoNT inhibits release of ___________ at presynaptic membrane of peripheral neurons; yields ____ ______
acetylcholine; flaccid paralysis
TeNT is transported in the __________ to inhibit interneuron function; yields _______ ______
CNS; spastic paralysis
Tetanus - C. tetani
Physiology:
Pathogenicity:
Physiology: anaerobe, proteolytic - peptide and amino acid
Pathogenicity: C. tetani is not invasive - remains at site of infection
- Following injury with a mixed infection (soil)
- Other bacteria ferment to reduce redox potential
- Allows limited growth of C. tetani, but sufficient for toxin production
Why do botulinum toxin and tetanus toxin elicit unique pathologies
BoNT enters through vescile and affects presynaptic neuron
TeNT has endosomal entry and follows retrograde trafficking to inhibit interneuron function
Treatment of tetanus toxin
Tetanus toxin → Tetanus toxoid (preventative)
Vaccinate Td or Tdap - stimulate an antibody response to toxin
Administer antibiotics
Administer anti-TT antibody (neutralize circulating toxin)
How are botulinum toxin serotypes defined?
Absence of cross neutralization by antisera
Most toxic protein toxins for humans
Botulinum toxin and Tetanus toxin
Which botulism serotypes are most common in humans
A, B and E
Three natural intoxications and infections associated with BoNT
- Food-borne (intoxicaton - toxin produced from food)
- Infant botulism (spores ingested)
- Wound botulism ( spores in wound)
Botulinum toxin implicated as agent of _____ ______
biological warfare
Are botulism and botulinum toxin contagious?
no
Treatment of botulinum toxin
- No licensed vaccine
- Supportive care
- Passive immunization and antitoxin
- CDC has anti- A,B, E sera: US army anti A-G sera
Why are BoNTs clinically useful
BoNTs have dual neuron specificity
- BoNTs bind specifically to receptors on neurons
- Cleave neuronal SNARE substrates
- High specifcity and potency for targeted neurons
Blepharospasm
Abnormal contraction or twitch of eyelid neurons (functional blindness)
Serotypes for Botox and Myoboc
Botox: Serotype A
Myoboc: Serotype B
