{"title":"The multifaceted roles of phosphoethanolamine-modified lipopolysaccharides: from stress response and virulence to cationic antimicrobial resistance.","authors":"Anna Schumann, Ahmed Gaballa, Martin Wiedmann","doi":"10.1128/mmbr.00193-23","DOIUrl":null,"url":null,"abstract":"<p><p>SUMMARYLipopolysaccharides (LPS) are an integral part of the outer membrane of Gram-negative bacteria and play essential structural and functional roles in maintaining membrane integrity as well as in stress response and virulence. LPS comprises a membrane-anchored lipid A group, a sugar-based core region, and an O-antigen formed by repeating oligosaccharide units. 3-Deoxy-D-<i>manno</i>-octulosonic acid-lipid A (Kdo<sub>2</sub>-lipid A) is the minimum LPS component required for bacterial survival. While LPS modifications are not essential, they play multifaceted roles in stress response and host-pathogen interactions. Gram-negative bacteria encode several distinct LPS-modifying phosphoethanolamine transferases (PET) that add phosphoethanolamine (pEtN) to lipid A or the core region of LPS. The <i>pet</i> genes differ in their genomic locations, regulation mechanisms, and modification targets of the encoded enzyme, consistent with their various roles in different growth niches and under varied stress conditions. The discovery of mobile colistin resistance genes, which represent lipid A-modifying <i>pet</i> genes that are encoded on mobile elements and associated with resistance to the last-resort antibiotic colistin, has led to substantial interest in PETs and pEtN-modified LPS over the last decade. Here, we will review the current knowledge of the functional diversity of pEtN-based LPS modifications, including possible roles in niche-specific fitness advantages and resistance to host-produced antimicrobial peptides, and discuss how the genetic and structural diversities of PETs may impact their function. An improved understanding of the PET group will further enhance our comprehension of the stress response and virulence of Gram-negative bacteria and help contextualize host-pathogen interactions.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0019323"},"PeriodicalIF":8.0000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbiology and Molecular Biology Reviews","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/mmbr.00193-23","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
SUMMARYLipopolysaccharides (LPS) are an integral part of the outer membrane of Gram-negative bacteria and play essential structural and functional roles in maintaining membrane integrity as well as in stress response and virulence. LPS comprises a membrane-anchored lipid A group, a sugar-based core region, and an O-antigen formed by repeating oligosaccharide units. 3-Deoxy-D-manno-octulosonic acid-lipid A (Kdo2-lipid A) is the minimum LPS component required for bacterial survival. While LPS modifications are not essential, they play multifaceted roles in stress response and host-pathogen interactions. Gram-negative bacteria encode several distinct LPS-modifying phosphoethanolamine transferases (PET) that add phosphoethanolamine (pEtN) to lipid A or the core region of LPS. The pet genes differ in their genomic locations, regulation mechanisms, and modification targets of the encoded enzyme, consistent with their various roles in different growth niches and under varied stress conditions. The discovery of mobile colistin resistance genes, which represent lipid A-modifying pet genes that are encoded on mobile elements and associated with resistance to the last-resort antibiotic colistin, has led to substantial interest in PETs and pEtN-modified LPS over the last decade. Here, we will review the current knowledge of the functional diversity of pEtN-based LPS modifications, including possible roles in niche-specific fitness advantages and resistance to host-produced antimicrobial peptides, and discuss how the genetic and structural diversities of PETs may impact their function. An improved understanding of the PET group will further enhance our comprehension of the stress response and virulence of Gram-negative bacteria and help contextualize host-pathogen interactions.
摘要脂多糖(LPS)是革兰氏阴性细菌外膜的一个组成部分,在维持膜完整性、应激反应和毒力方面发挥着重要的结构和功能作用。LPS 由膜锚定脂质 A 基团、糖基核心区和由重复寡糖单位形成的 O 抗原组成。3-Deoxy-D-manno-octulosonic acid-lipid A(Kdo2-lipid A)是细菌生存所需的最小 LPS 成分。虽然 LPS 修饰并非必不可少,但它们在应激反应和宿主-病原体相互作用中发挥着多方面的作用。革兰氏阴性细菌编码几种不同的 LPS 修饰磷乙醇胺转移酶(PET),可将磷乙醇胺(pEtN)添加到脂质 A 或 LPS 的核心区域。这些 PET 基因的基因组位置、调控机制和编码酶的修饰靶标各不相同,这与它们在不同生长环境和不同压力条件下的不同作用是一致的。移动可乐菌素抗性基因是在移动元件上编码的脂质 A 修饰 pet 基因,与对最后一种抗生素可乐菌素的抗性有关,该基因的发现在过去十年中引起了人们对 PET 和 pEtN 修饰 LPS 的极大兴趣。在这里,我们将回顾目前关于基于 pEtN 的 LPS 修饰功能多样性的知识,包括在特定生态位的适应优势和对宿主产生的抗菌肽的抗性方面可能发挥的作用,并讨论 PET 的遗传和结构多样性可能如何影响其功能。加深对 PET 组的了解将进一步提高我们对革兰氏阴性细菌的应激反应和毒力的理解,并有助于了解宿主与病原体之间相互作用的背景。
期刊介绍:
Microbiology and Molecular Biology Reviews (MMBR), a journal that explores the significance and interrelationships of recent discoveries in various microbiology fields, publishes review articles that help both specialists and nonspecialists understand and apply the latest findings in their own research. MMBR covers a wide range of topics in microbiology, including microbial ecology, evolution, parasitology, biotechnology, and immunology. The journal caters to scientists with diverse interests in all areas of microbial science and encompasses viruses, bacteria, archaea, fungi, unicellular eukaryotes, and microbial parasites. MMBR primarily publishes authoritative and critical reviews that push the boundaries of knowledge, appealing to both specialists and generalists. The journal often includes descriptive figures and tables to enhance understanding. Indexed/Abstracted in various databases such as Agricola, BIOSIS Previews, CAB Abstracts, Cambridge Scientific Abstracts, Chemical Abstracts Service, Current Contents- Life Sciences, EMBASE, Food Science and Technology Abstracts, Illustrata, MEDLINE, Science Citation Index Expanded (Web of Science), Summon, and Scopus, among others.