Streptococcus pyogenes malate degradation pathway links pH regulation and virulence.
Streptococcus pyogenes malate degradation pathway links pH regulation and virulence.
复制标题
化脓性链球菌苹果酸降解途径将 pH 调节和毒力联系起来。
DOI：
10.1128/iai.02814-14
复制
发表时间：
2015
影响因子：
3.1
通讯作者：
Caparon,MichaelG
中科院分区：
文献类型：
--
作者：
Paluscio,Elyse;Caparon,MichaelG
The ability of Streptococcus pyogenes to infect different niches within its human host most likely relies on its ability to utilize alternative carbon sources. In examining this question, we discovered that all sequenced S. pyogenes strains possess the genes for the malic enzyme (ME) pathway, which allows malate to be used as a supplemental carbon source for growth. ME is comprised of four genes in two adjacent operons, with the regulatory two-component MaeKR required for expression of genes encoding a malate permease (maeP) and malic enzyme (maeE). Analysis of transcription indicated that expression ofmaePandmaeEis induced by both malate and low pH, and induction in response to both cues is dependent on the MaeK sensor kinase. Furthermore, bothmaePEandmaeKRare repressed by glucose, which occurs via a CcpA-independent mechanism. Additionally, malate utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI–mutant fails to express the ME genes and is unable to utilize malate. Virulence of selected ME mutants was assessed in a murine model of soft tissue infection. MaeP–, MaeK–, and MaeR–mutants were attenuated for virulence, whereas a MaeE–mutant showed enhanced virulence compared to that of the wild type. Taken together, these data show that ME contributes to S. pyogenes' carbon source repertory, that malate utilization is a highly regulated process, and that a single regulator controls ME expression in response to diverse signals. Furthermore, malate uptake and utilization contribute to the adaptive pH response, and ME can influence the outcome of infection.
