Abstract

BackgroundThe global rise in the incidence of non-tuberculosis mycobacterial infections is of increasing concern due their high levels of intrinsic antibiotic resistance. Although integrated viral genomes, called prophage, are linked to increased antibiotic resistance in some bacterial species, we know little of their role in mycobacterial drug resistance.ResultsWe present here for the first time, evidence of increased antibiotic resistance and expression of intrinsic antibiotic resistance genes in a strain of Mycobacterium chelonae carrying prophage. Strains carrying the prophage McProf demonstrated increased resistance to amikacin. Resistance in these strains was further enhanced by exposure to sub-inhibitory concentrations of the antibiotic, acivicin, or by the presence of a second prophage, BPs. Increased expression of the virulence gene, whiB7, was observed in strains carrying both prophages, BPs and McProf, relative to strains carrying a single prophage or no prophages.ConclusionsThis study provides evidence that prophage alter expression of important mycobacterial intrinsic antibiotic resistance genes and additionally offers insight into the role prophage may play in mycobacterial adaptation to stress.

Highlights

  • The global rise in the incidence of non-tuberculosis mycobacterial infections is of increasing concern due their high levels of intrinsic antibiotic resistance

  • In this study we examine the impact of two mycobacteriophages on intrinsic antibiotic resistance and whiB7 expression in the non-tuberculosis mycobacterial pathogen, M. chelonae, a member of the M. abscessus/chelonae complex

  • BPs lysogens of the M. chelonae WT strain (BPs, McProf) appear to be more stable than BPs lysogens of M. smegmatis

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Summary

Introduction

The global rise in the incidence of non-tuberculosis mycobacterial infections is of increasing concern due their high levels of intrinsic antibiotic resistance. Integrated viral genomes, called prophage, are linked to increased antibiotic resistance in some bacterial species, we know little of their role in mycobacterial drug resistance. What was consistent in all clarithromycin-resistant isolates was elevated expression of genes in the whiB7 regulon, including the transcription factor whiB7 and its target genes, the drug efflux pumps plus other antibiotic resistance genes including erm and eis [7, 10,11,12]. These latter genes confer macrolide and aminoglycoside resistance, respectively. Characterizing the pathways that lead to increased whiB7 expression and intrinsic drug resistance in pathogenic mycobacteria will be important for identifying new targets for novel drug development [9, 16, 17]

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