Identifying the essential genes ofMycobacterium aviumsubsp.hominissuiswith Tn-Seq using a rank-based filter procedure

Abstract

AbstractMycobacterium avium(Mav) is increasingly recognized as a significant cause of morbidity, particularly in elderly patients or those with immune deficiency or underlying structural lung disease. Generally, Mav infection is treated with 2-3 antimicrobial drugs for at least 12 months. Identification of genes essential for Mav growth may yield novel strategies for improving curative therapy. We have generated saturating genome-wide transposon mutant pools in a commonly used laboratory strain ofMycobacterium aviumsubsp.hominissuis(MAC109) and developed a computational technique for classifying annotated genomic features as essential (ES), growth defect (GD), growth advantage (GA), or no-effect (NE) based on thein vitroeffect of disruption by transposon. We identified 270 features as ES with 230 of these overlapping with ES features inMycobacterium tuberculosis. These results may be useful for identifying drug targets or for informing studies requiring genetic manipulation ofMycobacterium avium, which should seek to avoid disrupting ES features to ensure bacterial viability.ImportanceMycobacterium avium subsp. hominissuisis an emerging cause of morbidity in vulnerable populations in many countries. It is known to be particularly difficult to treat, often requiring years of antibiotic therapy. In this study we report the genes ofMycobacterium aviumsubsp.hominissuisthat are required for the organism to growin vitro. Our findings may help guide future research into identifying new drugs to improve the treatment of this serious infection.