Dataset Information

A ?D-dependent antisense transcript modulates expression of the cyclic-di-AMP hydrolase GdpP in Bacillus subtilis.

ABSTRACT: Cyclic-di-AMP (c-di-AMP) is an essential second messenger in Bacillus subtilis, and depletion leads to defects in the integrity of the cell wall. Levels of c-di-AMP are regulated by both the rates of synthesis (by diadenylate cyclases) and the rates of degradation (by the GdpP phosphodiesterase, formerly YybT). Little is known about the regulation of gdpP expression or GdpP activity, but mutations that inactivate GdpP lead to high-level resistance to ?-lactam antibiotics. Here we demonstrate that expression of gdpP is regulated by a cis-acting antisense RNA (gdpP(as)) in vivo. Transcription of this antisense RNA is initiated in the middle of the gdp gene and is dependent on an alternative sigma factor, ?(D), previously associated with the expression of late flagellar genes, chemotaxis proteins and cell wall autolytic enzymes. Changes in ?(D) activity can modulate GdpP protein levels by ~2.5-fold, which may provide a mechanism for the cell to upregulate c-di-AMP levels in coordination with the activation of autolytic enzymes.

SUBMITTER: Luo Y

PROVIDER: S-EPMC4036058 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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A σD-dependent antisense transcript modulates expression of the cyclic-di-AMP hydrolase GdpP in Bacillus subtilis.

Luo Yun Y Helmann John D JD

Microbiology (Reading, England) 20120906 Pt 11

Cyclic-di-AMP (c-di-AMP) is an essential second messenger in Bacillus subtilis, and depletion leads to defects in the integrity of the cell wall. Levels of c-di-AMP are regulated by both the rates of synthesis (by diadenylate cyclases) and the rates of degradation (by the GdpP phosphodiesterase, formerly YybT). Little is known about the regulation of gdpP expression or GdpP activity, but mutations that inactivate GdpP lead to high-level resistance to β-lactam antibiotics. Here we demonstrate tha ...[more]

PMID: 22956758

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Project description:Streptococcus pneumoniae (the pneumococcus) is a naturally competent organism that causes diseases such as pneumonia, otitis media, and bacteremia. The essential bacterial second messenger cyclic di-AMP (c-di-AMP) is an emerging player in the stress responses of many pathogens. In S. pneumoniae, c-di-AMP is produced by a diadenylate cyclase, CdaA, and cleaved by phosphodiesterases Pde1 and Pde2. c-di-AMP binds a transporter of K+ (Trk) family protein, CabP, which subsequently halts K+ uptake via the transporter TrkH. Recently, it was reported that Pde1 and Pde2 are essential for pneumococcal virulence in mouse models of disease. To elucidate c-di-AMP-mediated transcription that may lead to changes in pathogenesis, we compared the transcriptomes of wild-type (WT) and Δpde1 Δpde2 strains by transcriptome sequencing (RNA-Seq) analysis. Notably, we found that many competence-associated genes are significantly upregulated in the Δpde1 Δpde2 strain compared to the WT. These genes play a role in DNA uptake, recombination, and autolysis. Competence is induced by a quorum-sensing mechanism initiated by the secreted factor competence-stimulating peptide (CSP). Surprisingly, the Δpde1 Δpde2 strain exhibited reduced transformation efficiency compared to WT bacteria, which was c-di-AMP dependent. Transformation efficiency was also directly related to the [K+] in the medium, suggesting a link between c-di-AMP function and the pneumococcal competence state. We found that a strain that possesses a V76G variation in CdaA produced less c-di-AMP and was highly susceptible to CSP. Deletion of cabP and trkH restored the growth of these bacteria in medium with CSP. Overall, our study demonstrates a novel role for c-di-AMP in the competence program of S. pneumoniaeIMPORTANCE Genetic competence in bacteria leads to horizontal gene transfer, which can ultimately affect antibiotic resistance, adaptation to stress conditions, and virulence. While the mechanisms of pneumococcal competence signaling cascades have been well characterized, the molecular mechanism behind competence regulation is not fully understood. The bacterial second messenger c-di-AMP has previously been shown to play a role in bacterial physiology and pathogenesis. In this study, we provide compelling evidence for the interplay between c-di-AMP and the pneumococcal competence state. These findings not only attribute a new biological function to this dinucleotide as a regulator of competence, transformation, and survival under stress conditions in pneumococci but also provide new insights into how pneumococcal competence is modulated.

Dataset Information

A ?D-dependent antisense transcript modulates expression of the cyclic-di-AMP hydrolase GdpP in Bacillus subtilis.

Publications

A σD-dependent antisense transcript modulates expression of the cyclic-di-AMP hydrolase GdpP in Bacillus subtilis.

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