Transcript (+) Virulence Factors and Diseases

Biology 431
Gram (+), Acid-Fast, and Wall-Less Rods
Chapters 25-27, 29, 44
Bacillus anthracis
Soil/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 Diseases
Limited 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 diphtheriae
Extremely 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).
Mycoplasma
Although 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