Apr 14, 2020

High-frequency switching between ON and OFF states in the phase variable modB methylase impacts gonococcal azithromycin susceptibility

BioRxiv : the Preprint Server for Biology
O. B. BrynildsrudVegard Eldholm

Abstract

The gonococcal adenine methylase modB, belonging to a Type III restriction modification system, is phase variable, but both the frequency of phase variation and phenotypic impact of phase variation is largely unknown. Here we show that modB switches between the ON and OFF states at a high frequency, with multiple transition events identified over the time scale of a single outbreak. Expanding our analyses, we find a clear association between modB status and azithromycin susceptibility. Among isolates lacking canonical 23S and mtrR promoter mutations, carrying modB in the ON configuration is strongly associated with increased azithromycin minimum inhibitory concentrations. Our findings suggest that modB adenine methylation controls the expression of genes modulating azithromycin susceptibility.

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