Lsr2 Is an Important Determinant of Intracellular Growth and Virulence in Mycobacterium abscessus

Discussion Lsr2, a unique nucleoid associated protein in the Actinomyces and Mycobacterium genera, has been extensively studied in M. tuberculosis (Colangeli et al., 2009; Gordon et al., 2010; Bartek et al., 2014). Like its ortholog H-NS, homodimers of Lsr2 can bind DNA cooperatively to form long oligomers on AT-rich sequences that can further interact to bridge distant DNA regions and contribute to loop formation (Chen et al., 2008; Liu and Gordon, 2012). At the genomic level, Lsr2 filaments are found at the promoters of 401 and 272 genes in M. tuberculosis and M. smegmatis, respectively, often extending into their coding regions (Gordon et al., 2010). This observation, as well as its known role as a negative regulator in several cellular functions, strongly suggest that like H-NS, Lsr2 represses transcription through promoter occlusion of RNA polymerase targets or by interfering with transcription elongation (Chen et al., 2008; Liu and Gordon, 2012; Landick et al., 2015). Lsr2 has been shown to be involved in M. tuberculosis virulence by binding to important genes, such as genes involved in the ESX secretion systems, the biosynthesis of the PDIM and PGL cell wall lipids or encoding antigenic proteins of the PE/PPE family (Gordon et al., 2010). Previous studies also demonstrated the implication of Lsr2 in multi-drug tolerance of M. tuberculosis (Colangeli et al., 2007) and in protection against reactive oxygen intermediates (Colangeli et al., 2009). All these phenotypes wer...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research