A 24-year-old man develops mild, nonexudative pharyngitis shortly after travel to Eastern Europe. Throat swab culture in tellurite-containing, selective media yields black, iridescent colonies. Microscopy shows club-shaped, gram-positive bacilli in a palisade arrangement, which are identified as nonpathogenic Corynebacterium diphtheriae. These bacteria can acquire virulence to become pathogenic through which of the following mechanisms?
Corynebacterium diphtheriae is a non-spore–forming, gram-positive bacillus that is transmitted primarily via aerosolized droplets. Nontoxigenic strains are minimally infectious; toxigenic strains are virulent and cause the clinical syndrome of diphtheria. Conversion from nontoxigenic to toxigenic C diphtheriae occurs due to infection with a lysogenic bacteriophage called Corynephage beta. This phage inserts the tox gene into the C diphtheriae genome, which results in the bacterial expression of the diphtheria AB toxin. Diphtheria toxin irreversibly halts protein synthesis due to ADP-ribosylation of elongation factor-2 and causes severe local (eg, pseudomembranous pharyngitis) and systemic (eg, myocarditis, neuritis) effects.
(Choice A) Conjugation is the direct transfer of plasmids from one bacterium to another through a pilus. Genes for antibiotic resistance are often transmitted in this manner.
(Choice B) Chromosomal mutations can theoretically lead to endotoxin production, but mutations more commonly lead to bacterial antibiotic resistance.
(Choice C) The gram-positive, spore-forming rods Bacillus and Clostridium generate toxins under environmental influences. The B anthracis spore, the causative agent in anthrax, survives in soil for extended periods in a state of dormancy. Only upon warming to 37° C in the presence of appropriate concentrations of CO2 and protein do the spores germinate and begin to synthesize toxin. The case is similar for C tetani spores, which germinate and produce toxin only in anaerobic environments, such as necrotic wounds.
(Choice E) Transformation involves the direct uptake of genetic material from the environment with subsequent incorporation into the bacterial genome. Streptococcus pneumoniae acquires the ability to produce capsules via transformation. The capsule is the major virulence factor for S pneumoniae; strains without the capsule are not pathogenic.
Educational objective:
Lysogenic bacteriophages are responsible for converting nonpathogenic Corynebacterium into toxigenic Corynebacterium. Toxigenic strains elaborate the diphtheria exotoxin, which causes pseudomembranous pharyngitis and potentially life-threatening systemic effects (eg, myocarditis, neuritis).