Abstract

Mycobacterial cell wall deficient/defective (CWD) forms occur in vivo in 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 tuberculosis and Mycobacterium avium subsp. paratuberculosis) and non-pathogenic (Mycobacterium smegmatis) mycobacteria in vitro converted to the CWD state by using lysozyme and glycine. Results highlighted that on the contrary to Mycobacterium smegmatis, the pathogenic species differentially regulated a repertoire of genes involved in mycobacterial virulence and persistence. In particular, Mycobacterium tuberculosis differentially regulated PE/PPE genes and many virulence genes such as Rv2351c plcA and Rv2962c that 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.

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