Intrahospital Infections Laboratory, Instituto de Salud Carlos III (ISCIII), National Centre for Microbiology, Madrid, Spain.
Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain.
Front Cell Infect Microbiol. 2023 Jan 13;12:1064053. doi: 10.3389/fcimb.2022.1064053. eCollection 2022.
is an important causative agent of hospital acquired infections. In addition to acquired resistance to many currently-available antibiotics, it is intrinsically resistant to fosfomycin. It has previously been shown that AmpD and AnmK contribute to intrinsic fosfomycin resistance in due to their involvement in the peptidoglycan recycling pathway. However, the role that these two enzymes play in the fitness and virulence of has not been studied. The aim of this study was to characterize several virulence-related phenotypic traits in mutants lacking AmpD and AnmK. Specifically, cell morphology, peptidoglycan thickness, membrane permeability, growth under iron-limiting conditions, fitness, resistance to disinfectants and antimicrobial agents, twitching motility and biofilm formation of the mutant strains ATCC 17978 Δ::Kan and Δ::Kan were compared to the wild type strain. Our results demonstrate that bacterial growth and fitness of both mutants were compromised, especially in the Δ::Kan mutant. In addition, biofilm formation was decreased by up to 69%, whereas twitching movement was reduced by about 80% in both mutants. These results demonstrate that, in addition to increased susceptibility to fosfomycin, alteration of the peptidoglycan recycling pathway affects multiple aspects related to virulence. Inhibition of these enzymes could be explored as a strategy to develop novel treatments for in the future. Furthermore, this study establishes a link between intrinsic fosfomycin resistance mechanisms and bacterial fitness and virulence traits.
是医院获得性感染的重要病原体。除了对许多现有的抗生素产生获得性耐药性外，它还对磷霉素具有固有耐药性。以前已经表明，AmpD 和 AnmK 通过参与肽聚糖回收途径，有助于固有磷霉素耐药性。然而，这两种酶在 的适应性和毒力中的作用尚未研究。本研究的目的是描述缺乏 AmpD 和 AnmK 的 突变体的几种与毒力相关的表型特征。具体而言，比较了突变菌株 ATCC 17978 Δ::Kan 和 Δ::Kan 的细胞形态、肽聚糖厚度、膜通透性、铁限制条件下的生长、适应性、对消毒剂和抗菌剂的抗性、翻滚运动和生物膜形成与野生型菌株。我们的结果表明，两种突变体的细菌生长和适应性都受到了损害，尤其是在 Δ::Kan 突变体中。此外，生物膜形成减少了高达 69%，而在两种突变体中翻滚运动减少了约 80%。这些结果表明，除了增加对磷霉素的敏感性外，肽聚糖回收途径的改变还会影响与毒力相关的多个方面。抑制这些酶可能成为未来开发 新治疗方法的一种策略。此外，本研究建立了固有磷霉素耐药机制与细菌适应性和毒力特征之间的联系。
