
<ArticleTitle>Association between erythromycin resistance and ability to enter human respiratory cells in group A streptococci.</ArticleTitle>
<AbstractText>BACKGROUND: An increase in erythromycin resistance rates among group A streptococci has been reported in some European countries. These bacteria, long thought to be extracellular pathogens, can be efficiently internalised by, and survive within, human cells of respiratory-tract origin. Macrolide antibiotics enter eukaryotic cells, whereas beta-lactams are essentially confined to the extracellular fluid. A protein encoded by gene <prot>prtF1</prot> is required for efficient entry of group A streptococci into epithelial cells. We investigated isolates of group A streptococci from children with pharyngitis in Italy for the presence of prtF1 and cell-invasion efficiency. METHODS: We investigated 74 erythromycin-resistant and 52 erythromycin-susceptible isolates collected throughout Italy in 1997-98 from children with pharyngitis. Erythromycin-resistance phenotypes (constitutive, inducible, and M) were assessed by the triple-disc test and resistance determinants (<prot>ermB</prot>, <prot>ermTR</prot>, and <prot>mefA</prot>) by PCR. All strains were examined for the presence of <prot>prtF1</prot> by PCR and for their ability to enter cultured human respiratory cells. FINDINGS: The proportion of prtF1-positive strains was significantly higher among erythromycin-resistant than susceptible strains (66 [89%] vs 11 [21%]; difference 68% [95% CI 52-84]). All erythromycin-resistant strains without <prot>prtF1</prot> were of the M phenotype. The proportion of highly cell-invasive isolates (invasion efficiency 10%) was significantly higher among erythromycin-resistant than among susceptible strains (59 [80%] vs five [10%]; difference 70% [57-83]). INTERPRETATIONS: The unsuspected association between erythromycin resistance and cell invasiveness in group A streptococci raises serious concern. Strains combining erythromycin resistance and ability to enter human respiratory-tract cells may be able to escape both beta-lactams by virtue of intracellular location and macrolides by virtue of resistance.</AbstractText>
