INTRODUCTION : Cigarette smoking is a well-recognized risk factor for development
of severe, invasive pneumococcal disease. However, little is known about the
direct effects of exposure to cigarette smoke on the virulence mechanisms of the
pathogen, particularly in respect of resistance to macrolide antibiotics, which are
widely used in the treatment of pneumococcal infection. This study aimed to
investigate the effects of exposure to cigarette smoke condensate (CSC, 80 and
160 mg/L) and clarithromycin (2 and 8 mg/L), alone and in combination in vitro,
on expression of the erm(B) and mef(A) macrolide resistance genes of strains 2507
and 521 (both serotype 23F), respectively, of the pneumococcus.
METHODS : Following exposure to CSC or clarithromycin, individually and in
combination, erm(B) and mef(A) gene expression were measured by sequential
extraction of RNA, conversion to and amplification of cDNA, and detection by
RESULTS : As expected, exposure of both test strains of the pneumococcus to
clarithromycin resulted in substantial upregulation of both macrolide resistance
genes, which was significantly (p<0.001) augmented by prior exposure to CSC in
the case of erm(B), but not mef(A). Somewhat unexpectedly, exposure of strain
2507 to CSC (160 mg/L) alone (in the absence of clarithromycin) also resulted
in significant (p<0.05) expression of the erm(B) gene.
CONCLUSIONS : Although the possible clinical significance remains to be established,
these findings suggest that smoking may impede the efficacy of macrolide-based antimicrobial therapy by accelerating the onset and magnitude of erm(B)-mediated
resistance, representing a novel pro-infective mechanism of smoking.