Background The 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. Results We 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. Conclusions This 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.

Diseases caused by mycobacteria such as Mycobacterium tuberculosis are the leading cause of death worldwide. With the emergence of strains that are resistant to first-line anti-tuberculosis drugs and naturally drug-resistant pathogens such as M. abscessus, there is a need to increase our understanding of mycobacterial fitness and virulence and identify new targets for drugs. The majority of the pathogenic species of the bacterial genus Mycobacterium, including M. tuberculosis, carry integrated viral genomes (prophages) that are hypothesized to contribute to virulence. Though we know many of the ways in which phage genes directly contribute to pathogenesis, e.g., the CTX prophage encodes the toxin in Vibrio cholera, we know little about the impact of phages that encode no obvious toxin or virulence gene. Using an RNAseq approach, our lab recently showed for the first time that the presence of a prophage alters the expression of 7.4% of genes in the pathogenic mycobacterial species, M. chelonae. The presence of prophage BPs increased the expression of genes in the whiB7 regulon, including whiB7, eis2, and tap, and decreased the expression of a padR-family transcription factor. BP lysogens were more resistant to aminoglycosides (kanamycin and amikacin) and tetracycline than wild-type strains of M. chelonae. In order to determine how the BP prophage drives changes in bacterial gene expression and phenotype, we will test the effects of individual BP genes expressed during lysogeny, such as the immunity repressor, on bacterial gene expression and antibiotic resistance phenotypes.

Background: The global increase 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. Results: We 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 prophage, BPs and McProf, relative to strains carrying a single prophage or no prophages. Conclusions: This 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.