Biology 431

Gram (+), Acid-Fast, and Wall-Less RodsChapters 25-27, 29, 44

Bacillus anthracisSoil/spores; historically - agriculture/veterinary disease

Virulence Factors

Antiphagocytic protein capsule - poly-D-glutamic acid

Protective Ag - binds receptor (broadly expressed)…

Binding initiates cleavage that form entry pores for…

LF: destroys MAP, leading to lysis - macrophage

EF: increases cAMP levels, leading to edema

One of two pathogenic species among 70 - with most virulence factor genes on plasmids pXO1-2.

Anthrax Diseases

Historically - agriculture and veterinary disease

Cutaneous: skin lesions, edema, 20% fatal/untreated

GI: nausea, vomiting, systemic, ~100% fatal/untreated

Inhaled: latency, systemic ~100% fatal /untreated

Treated with penicillin, ciprofloxacin - varying resistance

Vaccination of animals, animal workers, military

Only relative cereus causes some cases of diarrhea and ocular infections using 2-3 toxins.

Listeria monocytogenes

Soil, feces, plant decay; 5% people carry in GI tracts

Virulence Factors

INL protein - binds receptor, uptake, acid pH activates…

Listeriolysin O - phospholipase, releases to cytoplasm

Bacteria divide - propelled by ActA, nucleates host actin

Actin/bacteria shoot into neighboring cells - invasion

Outcome is movement into GI lining, MALT, macrophage; spreading to liver, spleen - systemic.

Listeria Diseases

Neonatal/Early: in utero,highly fatal systemic

Neonatal/Late: post-birth, meningitis and septicemia

Adults: flu-like bacteremia, GI, meningitis

Treated with penicillin; resistant to cephalosporins

Vaccination of animals, animal workers, military

Relative Erysipelothrix - skin infections or blood/endocarditis; prominent veterinary/agriculture.

Mycobacterium DiseasesLimited reservoirs for pathogens; poorly understood.

Virulence Factors

60% lipid/mycoloic acid wall - resistance, more in lab

Pigments/carotenes - can oxidize defensive chemicals

Quiescent? No spores - but spore-like genes? Latent?

Intracellular survival, alveolar macrophage - cord factor?

Unusually - NO known toxins… disease level:# agents

Injected TB test = PPDs that stimulate memory T cells

M. tuberculosis Disease

Defenses react - WBC, complement, O2 radicals…

Eventually, fibrin encapsulates, protects - Ca/tubercles

5% exposed develop active TB in 2 years (5-10% later)

10% if HIV, more likely to develop miliary (systemic)

Multidrug cocktail 6-9 months - isoniazid (wall-specific)

BCG (M. bovis) - live attenuated, efficacy? HIV?

M. leprae Disease - a.k.a. Hansen’s Disease

Spread by contact, armadillos only known US reservoir

Tuberculoid - strong T; granulomas, skin macules, mild

Lepromatous - strong Ab; dermal/nerves, disfiguring

Since 1985 - dropped by 90% worldwide, WHO efforts

M. avium Complex (MAC) Disease

Ubiquitous in water, plants, soil - ingested, inhaled…

Most serious in IC/AIDS - pneumonia, systemic

Even relatives like bovis - similar problems in IC/AIDS

Whole group of “rapidly growing” species (also soil and water) associated with wound infections, nosocomial.

Corynebacterium diphtheriaeExtremely prevalent in/on plants, animals as flora

Virulence Factors

Short-chain mycolic acid in wall (hint - Mycobacterium)

Only B-phage-lysogenized strains are virulent…

Tox gene makes A-B exotoxin - 1 of many examples…

B = binds host receptor, translocates protein into cell

A = catalytic, inactivates EF2 ribosome/translation factor

Host receptor = heart and nerve epidermal growth factor

Diphtheria Disease

Cutaneous: pre-existing breaks - worsening ulcer

Respiratory: 2-6 days - toxin damages pharynx…

Exudate, pseudomembrane, obstructed airway

Neutralizing IgG (blood exposure); toxoid DPT vaccine

Most relative species cause nosocomials (sepsis, UTI).

MycoplasmaAlthough wall-less, genetically related to Gram (+)

Virulence Factors and Diseases

Smallest - no cell wall but sterols, drug implications

Some surface Ag cross-react with human tissues

P1 binds host epithelial cilia - ciliostasis, cell death, SAg

pneumoniae - mild walking pneumonia, 2-6 weeks

genitalium - urethritis; hominis - PID, postpartum fever

Treated with non-wall drugs; condoms for STD’s