Defining the regulon of genes controlled by σ^E, a key regulator of the cell envelope stress response in Streptomyces coelicolor

Abstract

Summary The extracytoplasmic function (ECF) σ factor, σE, is a key regulator of the cell envelope stress response in Streptomyces coelicolor. Although its role in maintaining cell wall integrity has been known for over a decade, a comprehensive analysis of the genes under its control has not been undertaken. Here, using a combination of chromatin immunoprecipitation‐sequencing (ChIP‐seq), microarray transcriptional profiling and bioinformatic analysis, we attempt to define the σE regulon. Approximately half of the genes identified encode proteins implicated in cell envelope function. Seventeen novel targets were validated by S1 nuclease mapping or in vitro transcription, establishing a σE‐binding consensus. Subsequently, we used bioinformatic analysis to look for conservation of the σE target promoters identified in S. coelicolor across 19 Streptomyces species. Key proteins under σE control across the genus include the actin homolog MreB, three penicillin‐binding proteins, two L,D‐transpeptidases, a LytR‐CpsA‐Psr‐family protein predicted to be involved in cell wall teichoic acid deposition and a predicted MprF protein, which adds lysyl groups to phosphatidylglycerol to neutralize membrane surface charge. Taken together, these analyses provide biological insight into the σE‐mediated cell envelope stress response in the genus Streptomyces.

Physiological and Transcriptional Responses of Streptomyces albulus to Acid Stress in the Biosynthesis of ε-Poly-L-lysine

“…The transcription of SigE is not regulated by an anti-σ factor but completely controlled by the TCS, CseBC. Moreover, > 90% of transcription terminates directly downstream of the sigE gene (Tran et al, 2019). Therefore, the transcription levels of cseB and cseC show no significant difference in most instances.…”

“…Bacterial cell envelope, consist of cell wall and cell membranes, is an essential defensive barrier against various environmental stresses (Tran et al, 2019). Cell wall is the first barrier to contact with outside, which plays an important role against the adverse environment.…”

“…Besides, the transcription of pepD is regulated by SigE and the deletion of pepD or mprA/B upregulated the expression of sigE (He et al, 2006;Pang et al, 2007;White et al, 2010). However, there were some differences between both species, e.g., the pepD (MAGL005109) was located immediately upstream of mprA (MAGL005110) and mprB (MAGL005111) in S. albulus M-Z18, the transcription of sigE is completely controlled by the CseBC and the SigE regulon does not include pepD in Streptomyces (Tran et al, 2019). Notably, Pan L. et al (2019) proved that the signal transduction system of MprAB and PepD in S. albulus can regulate the transcription of pls.…”

“…As summarized in Table 1, 11 genes were expressed as stressresponse proteins. LytR family protein is predicted to be involved in cell wall teichoic acid deposition, which is controlled by SigE (Tran et al, 2019). The gene (lytR, MAGL008579) of LytR family regulatory protein was up-regulated under acid stress to stabilize cell wall.…”

Discovery of the extracytoplasmic function σ factors

“…After Lonetto et al () came out, my new postdoc Mark Paget and I continued to work on Streptomyces σ E and the cell envelope stress response that it controls (Paget et al , , Paget et al , ; Hong et al , ; Tran et al , ), but mostly shifted our attention to characterizing another ECF sigma we named σ R . We discovered that σ R controls the principal oxidative stress response in Streptomyces , and found that its activity was controlled by RsrA, a cytoplasmic, zinc‐dependent anti‐σ that exploits a thiol‐disulfide redox switch to sense and respond to oxidative stress (Paget et al , ; Kang et al , ; Paget et al , , Paget et al , ; Feeney et al , ).…”