Abstract
BackgroundNontuberculous mycobacterial (NTM) infections are increasing in prevalence, with current estimates suggesting that over 100,000 people in the United States are affected each year. It is unclear how certain species of mycobacteria transition from environmental bacteria to clinical pathogens, or what genetic elements influence the differences in virulence among strains of the same species. A potential mechanism of genetic evolution and diversity within mycobacteria is the presence of integrated viruses called prophages in the host genome. Prophages may act as carriers of bacterial genes, with the potential of altering bacterial fitness through horizontal gene transfer. In this study, we quantify the frequency and composition of prophages within mycobacteria isolated from clinical samples and compare them against the composition of PhagesDB, an environmental mycobacteriophage database.MethodsProphages were predicted by agreement between two discovery tools, VirSorter and Phaster, and the frequencies of integrated prophages were compared by growth rate. Prophages were assigned to PhagesDB lettered clusters. Bacterial virulence gene frequency was calculated using a combination of the Virulence Factor Database (VFDB) and the Pathosystems Resource Integration Center virulence database (Patric-VF) within the gene annotation software Prokka. CRISPR elements were discovered using CRT. ARAGORN was used to quantify tRNAs.ResultsRapidly growing mycobacteria (RGM) were more likely to contain prophage than slowly growing mycobacteria (SGM). CRISPR elements were not associated with prophage abundance in mycobacteria. The abundance of tRNAs was enriched in SGM compared to RGM.We compared the abundance of bacterial virulence genes within prophage genomes from clinical isolates to mycobacteriophages from PhagesDB. Our data suggests that prophages from clinical mycobacteria are enriched for bacterial virulence genes relative to environmental mycobacteriophage from PhagesDB.ConclusionProphages are present in clinical NTM isolates. Prophages are more likely to be present in RGM compared to SGM genomes. The mechanism and selective advantage of this enrichment by growth rate remain unclear. In addition, the frequency of bacterial virulence genes in prophages from clinical NTM is enriched relative to the PhagesDB environmental proxy. This suggests prophages may act as a reservoir of genetic elements bacteria could use to thrive within a clinical environment.
Highlights
Nontuberculous mycobacterial (NTM) infections can cause serious pulmonary disease that may become chronic and affect quality of life even leading to death [1]
We found that bacterial virulence genes are more likely to be present within prophage elements derived from clinical sources than from all mycobacteriophage genomes in PhagesDB isolated from the environmental M. smegmatis and the subset selected from lysogenic mycobacteriophages (F = 8.89, p = 6.16e-19 and F = 6.73, p = 1.73e-11, proportions ztest, Fig. 4)
The number of prophages found in this study within mycobacteria with a rapid growth rate is greater relative to the number found in slowly growing mycobacteria (Fig. 1)
Summary
Nontuberculous mycobacterial (NTM) infections can cause serious pulmonary disease that may become chronic and affect quality of life even leading to death [1]. The mechanism by which these organisms, which have long been recognized as environmental, become clinical pathogens is an active area of research with prior studies exploring host susceptibility [5], geographic factors [6], and changes in genetic composition [7]. Nontuberculous mycobacterial (NTM) infections are increasing in prevalence, with current estimates suggesting that over 100,000 people in the United States are affected each year. It is unclear how certain species of mycobacteria transition from environmental bacteria to clinical pathogens, or what genetic elements influence the differences in virulence among strains of the same species. We quantify the frequency and composition of prophages within mycobacteria isolated from clinical samples and compare them against the composition of PhagesDB, an environmental mycobacteriophage database
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