Modulatory Impact of the sRNA Mcr11 in Two Clinical Isolates of Mycobacterium tuberculosis

Mycobacterium tuberculosis complex molecular networks and their regulation: Implications of strain heterogeneity on epigenetic diversity and transcriptome regulation

“…Thus, there are still many gaps in understanding how each of the ∼4000 genes of M. tuberculosis are regulated and their roles in virulence and pathogenesis through uncovering the mechanisms of their regulators. Only recently, a strain-specific perspective on sRNA gene regulation and phenotype has been characterized [ 96 ] on M. tuberculosis clinical strains oof Columbian origin and this is an area that still needs to be further investigated within the members of MTBC. In conclusion, there is still a lot more to uncover in order to understand MTBC clinically relevant strains and the consequence of their genetic heterogeneity in gene regulatory mechanisms through non-coding RNAs and epigenetic modulation during different stages of growth and during infection of different models.…”

“…Despite this high degree of genetic conservation in MTBC strains, differential pathogen transcriptome changes during in vitro macrophages infection [ 26 ], cholesterol rich media [ 95 ] and in vivo infection [ 90 ], suggesting “unique’ gene regulation by sRNAs has been reported. Recently, Alvarez-Eraso et al [ 96 ] showed that silencing Mcr11 sRNAs in two Colombian clinical strains (UT127 and UT205) and a laboratory H37Rv strain induce distinct growth phenotype. The H37Rv and UT127 strains showed delayed growth patterns, while growth was inhibited in the UT205 strain, which also exhibited a clumping phenotype.…”

“…Furthermore, upon transcriptome interrogation during Mcr11 silencing, the laboratory H37Rv and UT127 strain showed similar gene regulation patterns, which vastly differed from the UT205 strain. The “unique” UT205 transcriptional signatures may be associated with reduction in macrophage cell death compared to the wild type of the same strain [ 96 ], which may provide better insight into strain-specific M. tuberculosis virulent-specific sRNAs. Understanding the mechanisms of virulent-specific sRNAs in clinically relevant MTBC strains will be a step closer to designing novel tools to control the growth and virulence of this “notorious” pathogen with a strain-specific perspective of the MTBC lineages.…”