Anaerobic & Toxin-Producing Pathogens

Oxygen & Metabolism

Oxygen: accepts electrons from the electron transport chain during aerobic respiration

Oxygen can be toxic → reactive oxygen species

Through catalyzation, in the body it creates hydrogen peroxide

Bacteria have varying levels of oxygen tolerance

Some need it to live, others it kills (strict obligate anaerobic)

Ways bacteria make energy without oxygen for metabolism

Shift to fermentative metabolism

Use an alternate electron acceptor such as nitrogen

Obligate Aerobe

Absolute requirement for oxygen to respire, produce ATP, and grow

I.e. Mycobacterium tuberculosis

Facultative Aerobe/Anaerobe

Can use oxygen to respire and produce ATP, but can also switch to fermentation or anaerobic respiration in the absence of oxygen

I.e. streptococci, staphylococci, and enterics

Microaerophilile

Require oxygen to respire and produce ATP, but are only tolerant of lower oxygen levels (2-5% Oxygen)

I.e. Campylobacter species

Obligate Anaerobe

Killed by atmospheric oxygen levels, use anaerobic respiration pathways to produce ATP (fermentation/nitrogen as electron acceptor)

I.e. Clostridia, botulinum, etc

Anaerobic Infections

Infections caused by a miscellaneous group of both gram-negative and gram-positive anaerobic bacteria

Diagnosis: challenging due to polymicrobial nature of infections, as well as the fastidious and slow growth of anaerobic bacteria

Treatment: hyperbaric oxygen, surgical debridement, and antibiotics (often metronidazole)

Common Anaerobic Infections

Bacterial vaginosis: due to overgrowth of anaerobic bacteria in the vagina

Abscesses and some skin and soft tissue infections

Intra-abdominal infections

Oral infections (periodontitis)

Some chronic pulmonary infections

Clostridium (general)

Large, spore-forming gram-positive bacilli

Obligate anaerobes, vegetative cells killed by oxygen, spores are able to survive long periods of air exposure

Found in soils, aquatic sediments and intestinal tracts of animals, most are harmless

Pathogens: X. perfringens, difficile, botulinum, tetani

All produce toxins which are the primary cause of disease symptoms

Toxin-Mediated Infections

Infection where pathogenesis is primarily or solely due to the action of a secreted toxin (exotoxin)

Severity of reaction to toxin is dependent on what the exotoxin is composed of (usually proteins)

Non-toxigenic strains either do not cause disease, or disease is much less severe

Extracellular pathogenic strategy

In most cases, toxin is effective at eliciting protective immunity and is the basis of several current vaccinations

Clostridium difficile (General)

Disease: antibiotic-associated (usually nosocomial) diarrhea and pseudomembranous colitis

Infection results from overgrowth C. difficile in the colon, often after extended antibiotic therapy

Major issue of recurrence after initial treatment (tends to come back repeatedly due to toxins)

Non-invasive disease resulting from exotoxin production

Toxin A: enterotoxin, causes fluid accumulation in the bowel

Toxin B: lethal cytotoxin, used to diagnose disease

Clostridium difficile (Prevention, Diagnosis, Treatment)

Prevention: antimicrobial stewardship; handwashing

Diagnosis: hx of antibiotic use + detection of toxins with commercial assay

Treatment: Often resistant to clindamycin and fluoroquinolones,

Switch patients to effect antibiotics (Vance, fluoro's)

Antibody-based therapies targeting toxin A and toxin B in several clinical trials that drastically reduce recurrence; administered alongside antibiotics

Fecal transplants have shown promise to prevent recurrence

Fecal transplant + antibiotics reduced recurrence rates of C. difficile in studies

Clostridium perfringens (General)

One of the most common causes of food poisoning in US

Spores not killed by cooking, can germinate and grow if cooked food is not served immediately

Outbreaks usually linked to institutions

Also can infect surgical or traumatic wounds and cause gas gangrene (mynecrosis) and other soft tissue infections

Clostridium perfringens (Prevention, Diagnosis, Treatment)

Diagnosis: Culture from implicated food, wound, or stool sample; often stain "gram variable" and/or Nagler's reaction on egg yolk media plate due to action of the alpha toxin

Treatment: Food poisoning is often self-limiting, but Gas gangrene- penicillin, metronidazole, and chloramphenicol

Prevention: Proper food handling, proper cleaning and debridement of wounds, leave uncleaned wounds open

A-B Toxins

Two component protein complex secreted by pathogenic bacteria

Type of exotoxin reliant on two subunits for activity:

A subunit: enzymatically active and determines the type of damage

B subunit: required for binding to and receptor-mediated endocytosis into host cells (determines who gets sick)

Used by many extracellular pathogens to mediate disease

Clostridium botulinum (General)

Causative agent of botulism: largely toxigenic disease (no accompanying infection) in healthy diseases

Virulence Factor

Botulism Toxin: seven types of disease (A-G)

Toxin is ingested, absorbed in the GI tract, and travels in the blood stream to peripheral neuromuscular synapses

A-B toxin: a fragment is a heat-labile zinc peptidase that blocks the release of acetylcholine, which is required to stimulate the muscles

Results in flaccid paralysis

Binding is irreversible, and recovery requires regeneration of the nerve endings

Supportive care + antitoxin

Clostridium botulinum (Prevention, Diagnosis, Treatment)

Diagnosis: treatment based on clinical symptoms, particularly likely when a cluster of cases of acute flaccid paralysis appears + differentiate from other neuropathies (Guillain-Barre, meningitis) by laboratory identification of toxin/organism in serum, stool, and food

Prevention: proper food handling and preparation

No honey for children under 1 year of age

Treatment: Antitoxin: for food-borne botulism

Antibiotics + Antitoxin for infant botulism

Clostridium tetani (General)

Ubiquitous in soil and colonizes GI tract of humans and animals

Common in underdeveloped countries due to lack of immunization

Very few cases in the U.S., usually are elderly patients due to waning immunity

Clostridium tetani (Prevention, Diagnosis, Treatment)

Prevention

Vaccination with tetanus toxoid (Tdap, Dtap)

Treatment

Wound care, antibiotics, and tetanus anti-toxin

Clostridium perfringens (Pathogenesis)

Common inhabitant of intestinal tract of humans, animals, and found in the soil

Five types A-E found in human intestinal tract

Type A is most often associated with human diseases, disease dependent on specific exotoxins

Clostridial food poisoning: dependent on the action of C. perfringens type C enterotoxin (CPE)

Necrotizing enteritis: rare condition caused by C. perfringens type C which secrete ulcerative beta toxin

Gas gangrene: a skin and soft tissue infection (SSTI) due to numerous secreted toxins and extracellular enzymes, including an alpha toxin

Food-borne botulism

Intoxication by contaminated food

Symptoms appear 12-72 hours after ingestion

Blurred vision, dry mouth, constipation, abdominal pain, followed by flaccid paralysis, descending weakness of the peripheral and respiratory muscles

Infant Botulism

Most common type seen in the US: infection

Infection of the large intestine, where bacteria produce toxin, prior to establishment of normal flora

Symptoms: appear 3-30 days after ingestion

Causes weak suckling ability, failure to thrive, "floppy baby" syndrome

Clostridium tetani (Pathogenesis)

Spores germinate when introduced into puncture wounds or lacerations; incubation period ranging from a few days to weeks

Bacteria multiplies at site of inoculation, releases tetanus toxin that causes disease

Clinical presentation most commonly begins with lockjaw, and other symptoms follow in a descending pattern

Clostridium tetani (Virulence Factors-Toxin)

Tetanus toxin (tetanospasmin) released upon bacterial cell lysis, Travels from site of infection by neural synapses to central nervous system

A-B toxin: a fragment is a zinc-peptidase that blocks the release of inhibitory neurotransmitters (GABA)

Unchecked nervous impulses result in muscular spasms - spastic paralysis

Binding is irreversible, recovery dependent upon regeneration of new axonal terminals

Requires antitoxin also