Differentially expressed genes in mycobacterial cell wall deficient forms inducedin vitro

Mycobacterial cell wall deficient/defective (CWD) forms occurin vivoin response to various antimicrobial factors such as lysozyme released by the host or antibiotics. A wide body of research suggests that these forms are clinically significant and involved in the establishment of either subclinical or chronic infections due to their ability to resist host defenses mechanisms. Although CWD mycobacteria have been isolated from patients with several diseases, their effective role in pathogenesis is still unknown due to the difficulties in handling these pleomorphic forms. In this study, whole-genome microarrays have been used to identify for the first time differentially expressed genes of both pathogenic (Mycobacterium tuberculosisandMycobacterium aviumsubsp.paratuberculosis) and non-pathogenic (Mycobacterium smegmatis) mycobacteriain vitroconverted to the CWD state by using lysozyme and glycine. Results highlighted that on the contrary toMycobacterium smegmatis, the pathogenic species differentially regulated arepertoireof genes involved in mycobacterial virulence and persistence. In particular,Mycobacterium tuberculosisdifferentially regulated PE/PPE genes and many virulence genes such asRv2351c plcAandRv2962cthat are highly specific for this species. Hence, the CWD state may represents an important stage in the life-cycle of pathogenic mycobacteria that potentially drives persistence.