The role of Listeria monocytogenes PstA in β-lactam resistance requires the cytochrome bd oxidase activity.

IF 2.7 3区 生物学 Q3 MICROBIOLOGY Journal of Bacteriology Pub Date : 2024-08-22 Epub Date: 2024-07-12 DOI:10.1128/jb.00130-24
Zepeng Tu, David M Stevenson, Darrel McCaslin, Daniel Amador-Noguez, TuAnh N Huynh
{"title":"The role of <i>Listeria monocytogenes</i> PstA in β-lactam resistance requires the cytochrome <i>bd</i> oxidase activity.","authors":"Zepeng Tu, David M Stevenson, Darrel McCaslin, Daniel Amador-Noguez, TuAnh N Huynh","doi":"10.1128/jb.00130-24","DOIUrl":null,"url":null,"abstract":"<p><p>c-di-AMP is an essential second messenger that binds and regulates several proteins of different functions within bacterial cells. Among those, PstA is a structurally conserved c-di-AMP-binding protein, but its function is largely unknown. PstA is structurally similar to PII signal transduction proteins, although it specifically binds c-di-AMP rather than other PII ligands such as ATP and α-ketoglutarate. In <i>Listeria monocytogenes</i>, we found that PstA increases β-lactam susceptibility at normal and low c-di-AMP levels, but increases β-lactam resistance upon c-di-AMP accumulation. Examining a PstA mutant defective for c-di-AMP binding, we found the apo form of PstA to be toxic for β-lactam resistance, and the c-di-AMP-bound form to be beneficial. Intriguingly, a role for PstA in β-lactam resistance is only prominent in aerobic cultures, and largely diminished under hypoxic conditions, suggesting that PstA function is linked to aerobic metabolism. However, PstA does not control aerobic growth rate, and has a modest influence on the tricarboxylic acid cycle and membrane potential-an indicator of cellular respiration. The regulatory role of PstA in β-lactam resistance is unrelated to reactive oxygen species or oxidative stress. Interestingly, during aerobic growth, PstA function requires the cytochrome <i>bd</i> oxidase (CydAB), a component of the respiratory electron transport chain. The requirement for CydAB might be related to its function in maintaining a membrane potential, or redox stress response activities. Altogether, we propose a model in which apo-PstA diminishes β-lactam resistance by interacting with an effector protein, and this activity can be countered by c-di-AMP binding or a by-product of redox stress.</p><p><strong>Importance: </strong>PstA is a structurally conserved c-di-AMP-binding protein that is broadly present among Firmicutes bacteria. Furthermore, PstA binds c-di-AMP at high affinity and specificity, indicating an important role in the c-di-AMP signaling network. However, the molecular function of PstA remains elusive. Our findings reveal contrasting roles of PstA in β-lactam resistance depending on c-di-AMP-binding status. We also define physiological conditions for PstA function during aerobic growth. Future efforts can exploit these conditions to identify PstA interaction partners under β-lactam stress.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0013024"},"PeriodicalIF":2.7000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340317/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Bacteriology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/jb.00130-24","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/12 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

c-di-AMP is an essential second messenger that binds and regulates several proteins of different functions within bacterial cells. Among those, PstA is a structurally conserved c-di-AMP-binding protein, but its function is largely unknown. PstA is structurally similar to PII signal transduction proteins, although it specifically binds c-di-AMP rather than other PII ligands such as ATP and α-ketoglutarate. In Listeria monocytogenes, we found that PstA increases β-lactam susceptibility at normal and low c-di-AMP levels, but increases β-lactam resistance upon c-di-AMP accumulation. Examining a PstA mutant defective for c-di-AMP binding, we found the apo form of PstA to be toxic for β-lactam resistance, and the c-di-AMP-bound form to be beneficial. Intriguingly, a role for PstA in β-lactam resistance is only prominent in aerobic cultures, and largely diminished under hypoxic conditions, suggesting that PstA function is linked to aerobic metabolism. However, PstA does not control aerobic growth rate, and has a modest influence on the tricarboxylic acid cycle and membrane potential-an indicator of cellular respiration. The regulatory role of PstA in β-lactam resistance is unrelated to reactive oxygen species or oxidative stress. Interestingly, during aerobic growth, PstA function requires the cytochrome bd oxidase (CydAB), a component of the respiratory electron transport chain. The requirement for CydAB might be related to its function in maintaining a membrane potential, or redox stress response activities. Altogether, we propose a model in which apo-PstA diminishes β-lactam resistance by interacting with an effector protein, and this activity can be countered by c-di-AMP binding or a by-product of redox stress.

Importance: PstA is a structurally conserved c-di-AMP-binding protein that is broadly present among Firmicutes bacteria. Furthermore, PstA binds c-di-AMP at high affinity and specificity, indicating an important role in the c-di-AMP signaling network. However, the molecular function of PstA remains elusive. Our findings reveal contrasting roles of PstA in β-lactam resistance depending on c-di-AMP-binding status. We also define physiological conditions for PstA function during aerobic growth. Future efforts can exploit these conditions to identify PstA interaction partners under β-lactam stress.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
单核细胞增生李斯特菌 PstA 在抗β-内酰胺过程中的作用需要细胞色素 bd 氧化酶的活性。
c-di-AMP 是一种重要的第二信使,可与细菌细胞内多种不同功能的蛋白质结合并对其进行调控。其中,PstA 是一种结构上保守的 c-di-AMP 结合蛋白,但其功能在很大程度上还不为人所知。PstA 在结构上与 PII 信号转导蛋白相似,但它专门结合 c-di-AMP 而不是其他 PII 配体,如 ATP 和 α-酮戊二酸。在单核细胞增生李斯特菌中,我们发现 PstA 在正常和低 c-di-AMP 水平下会增加对β-内酰胺类药物的敏感性,但在 c-di-AMP 积累时会增加对β-内酰胺类药物的抗性。通过研究 c-di-AMP 结合缺陷的 PstA 突变体,我们发现 PstA 的 apo 形式对β-内酰胺抗性具有毒性,而 c-di-AMP 结合形式则有益。耐人寻味的是,PstA 在β-内酰胺抗性中的作用仅在有氧培养中突出,在缺氧条件下基本减弱,这表明 PstA 的功能与有氧代谢有关。然而,PstA 并不控制有氧生长速率,对三羧酸循环和膜电位(细胞呼吸的指标)的影响不大。PstA 在抗β-内酰胺过程中的调控作用与活性氧或氧化应激无关。有趣的是,在有氧生长过程中,PstA 的功能需要细胞色素 bd 氧化酶(CydAB),它是呼吸电子传递链的一个组成部分。对 CydAB 的需求可能与其维持膜电位的功能或氧化还原应激反应活动有关。总之,我们提出了一个模型,在该模型中,apo-PstA通过与效应蛋白相互作用来降低β-内酰胺抗性,而这种活性可以通过c-di-AMP结合或氧化还原应激的副产物来抵消:PstA是一种结构保守的c-di-AMP结合蛋白,广泛存在于真菌中。此外,PstA 与 c-di-AMP 的结合具有高亲和力和特异性,表明其在 c-di-AMP 信号网络中发挥着重要作用。然而,PstA 的分子功能仍然难以捉摸。我们的研究结果揭示了 PstA 根据 c-di-AMP 结合状态在β-内酰胺耐药性中的不同作用。我们还确定了 PstA 在有氧生长过程中发挥作用的生理条件。未来的工作可以利用这些条件来确定在β-内酰胺胁迫下 PstA 的相互作用伙伴。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Journal of Bacteriology
Journal of Bacteriology 生物-微生物学
CiteScore
6.10
自引率
9.40%
发文量
324
审稿时长
1.3 months
期刊介绍: The Journal of Bacteriology (JB) publishes research articles that probe fundamental processes in bacteria, archaea and their viruses, and the molecular mechanisms by which they interact with each other and with their hosts and their environments.
期刊最新文献
CodY controls the SaeR/S two-component system by modulating branched-chain fatty acid synthesis in Staphylococcus aureus. Impact of high-speed nanodroplets on various pathogenic bacterial cell walls. Vibrio cholerae: a fundamental model system for bacterial genetics and pathogenesis research. A flagellar accessory protein links chemotaxis to surface sensing. Combinatorial control of type IVa pili formation by the four polarized regulators MglA, SgmX, FrzS, and SopA.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1