Malate-Mediated Carbon Catabolite Repression in Bacillus subtilis Involves the HPrK/CcpA Pathway

Meyer, Frederik M.; Jules, Matthieu; Mehne, Felix M.P.; Coq, Dominique Le; Landmann, Jens J.; Görke, Boris; Aymerich, Stéphane; Stülke, Jörg

doi:10.1128/jb.06197-11

Cited by 37 publications

(25 citation statements)

References 58 publications

(87 reference statements)

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“…In this respect, it is noteworthy that the glycerol kinase GlpK requires phosphorylation by HPr for glycerol utilization (48,52). Malate is a preferred carbon source for B. subtilis and is known to influence the carbon catabolite repression response (53). In this context, it is noteworthy that a decrease in antimicrobial activity was also reported for glycocin F upon supplementation of the medium with GlcNAc, which is the sugar that is attached to glycocin F at two positions (17).…”

Section: Sublancin Displays Submicromolar Mics Againstmentioning

confidence: 99%

The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

Gonzalo

Denham

Mars

et al. 2015

Antimicrob Agents Chemother

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The mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) of Bacillus species as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such as Bacillus species and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin. Bacteriocins are ribosomally synthesized peptides produced by a wide range of bacterial species. These bacteriocins endow the producing bacteria with a competitive advantage in their respective niche. Many bacteriocins are heavily posttranslationally processed during their biosynthesis, and these modifications are required for activity (1). Nisin is the best-studied bacteriocin and belongs to the lantibiotic family (2). The mode of action of nisin involves binding to lipid II, which prevents further cell wall synthesis, followed by the formation of pores within the membrane. The leakage of essential metabolites from these cells results in death of the bacteria. Targeting of lipid II by bacteriocins is a common mechanism of action (3-5). Other mechanisms include the targeting of phosphotransferase systems (6, 7), acting as Trojan horses (8, 9), parasitizing iron uptake pathways (10) and causing the collapse of membrane potential, together with leakage of ions and/or a decrease in intracellular ATP concentrations (11). There is much interest in bacteriocins for use in the control of bacterial infections and therefore in their mechanisms of action.Sublancin is a bacteriocin produced by the Gram-positive soil bacterium Bacillus subtilis strain 168. It is capable of killing several species of Gram-positive bacteria, such as Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) (12). Sublancin is encoded by the sunA gene on the SP␤ prophage as a prepeptide (13). The genes necessary for the synthesis of sublancin are also included in this region and are expressed from two promoters. The biosynthetic operon is made up of five individual genes, which are responsible for producing active sublancin. The sunT gene is responsible for the export of sublancin and cleavage of its leader sequence. Two thiol-disulfide oxidoreductases, encoded by bdbA (the only gene of the operon that is dispensable for active sublancin production) and bdbB, are responsible for creating the two disulfide bonds of sublancin. These disulfide bonds involve four of the five cysteine re...

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Section: Sublancin Displays Submicromolar Mics Againstmentioning

confidence: 99%

The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

Gonzalo

Denham

Mars

et al. 2015

Antimicrob Agents Chemother

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“…At present, it is unclear how this relates to NTP concentrations in vivo. The ATP concentration was recently reported to be ∼60 µM in exponentially growing B. subtilis cells (Meyer et al 2011), whereas 1-3 mM was reported for intracellular GTP (Ratnayake- Lecamwasam et al 2001). Yet, the ATP concentration was measured to be three-to fourfold higher than for the other three NTPs (Lopez et al 1979).…”

Section: Prna Synthesis As a Function Of Ntp Concentrationmentioning

confidence: 99%

Mechanistic comparison of Bacillus subtilis 6S-1 and 6S-2 RNAs—commonalities and differences

Burenina

Hoch

Damm

et al. 2014

RNA

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Bacterial 6S RNAs bind to the housekeeping RNA polymerase (σ A -RNAP in Bacillus subtilis) to regulate transcription in a growth phase-dependent manner. B. subtilis expresses two 6S RNAs, 6S-1 and 6S-2 RNA, with different expression profiles. We show in vitro that 6S-2 RNA shares hallmark features with 6S-1 RNA: Both (1) are able to serve as templates for pRNA transcription; (2) bind with comparable affinity to σ A -RNAP; (3) are able to specifically inhibit transcription from DNA promoters, and (4) can form stable 6S RNA:pRNA hybrid structures that (5) abolish binding to σ A -RNAP. However, pRNAs of equal length dissociate faster from 6S-2 than 6S-1 RNA, owing to the higher A,U-content of 6S-2 pRNAs. This could have two mechanistic implications: (1) Short 6S-2 pRNAs (<10 nt) dissociate faster instead of being elongated to longer pRNAs, which could make it more difficult for 6S-2 RNA-stalled RNAP molecules to escape from the sequestration; and (2) relative to 6S-1 RNA, 6S-2 pRNAs of equal length will dissociate more rapidly from 6S-2 RNA after RNAP release, which could affect pRNA turnover or the kinetics of 6S-2 RNA binding to a new RNAP molecule. As 6S-2 pRNAs have not yet been detected in vivo, we considered that cellular RNAP release from 6S-2 RNA might occur via 6S-1 RNA displacing 6S-2 RNA from the enzyme, either in the absence of pRNA transcription or upon synthesis of very short 6S-2 pRNAs (∼5-mers, which would escape detection by deep sequencing). However, binding competition experiments argued against these possibilities.

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“…For example, malate is a second preferred carbon source for Bacillus subtilis. It is rapidly coutilized with glucose and strongly represses the uptake of alternative carbon sources (20,33). On the other hand, in Lactobacillus casei, malate metabolism was reported to be repressed by the presence of glucose in the medium (23).…”

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confidence: 99%

Fine-Tuned Transcriptional Regulation of Malate Operons in Enterococcus faecalis

Mortera

Espariz

Suárez

et al. 2012

Appl Environ Microbiol

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eIn Enterococcus faecalis, the mae locus is constituted by two putative divergent operons, maePE and maeKR. The first operon encodes a putative H ؉ /malate symporter (MaeP) and a malic enzyme (MaeE) previously shown to be essential for malate utilization in this bacterium. The maeKR operon encodes two putative proteins with significant similarity to two-component systems involved in sensing malate and activating its assimilation in bacteria. Our transcriptional and genetic assays showed that maePE and maeKR are induced in response to malate by the response regulator MaeR. In addition, we observed that both operons were partially repressed in the presence of glucose. Accordingly, the cometabolism of this sugar and malate was detected. The binding of the complex formed by CcpA and its corepressor P-Ser-HPr to a cre site located in the mae region was demonstrated in vitro and explains the carbon catabolite repression (CCR) observed for the maePE operon. However, our results also provide evidence for a CcpA-independent CCR mechanism regulating the expression of both operons. Finally, a biomass increment of 40 or 75% was observed compared to the biomass of cells grown only on glucose or malate, respectively. Cells cometabolizing both carbon sources exhibit a higher rate of glucose consumption and a lower rate of malate utilization. The growth improvement achieved by E. faecalis during glucose-malate cometabolism might explain why this microorganism employs different regulatory systems to tightly control the assimilation of both carbon sources.

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Malate-Mediated Carbon Catabolite Repression in Bacillus subtilis Involves the HPrK/CcpA Pathway

Cited by 37 publications

References 58 publications

The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

Mechanistic comparison of Bacillus subtilis 6S-1 and 6S-2 RNAs—commonalities and differences

Fine-Tuned Transcriptional Regulation of Malate Operons in Enterococcus faecalis

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