Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide 5005, South Australia, Australia.
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3000, Victoria, Australia.
Int J Mol Sci. 2019 Jan 29;20(3):575. doi: 10.3390/ijms20030575.
has emerged as one of the leading causative agents of nosocomial infections. Due to its high level of intrinsic and adapted antibiotic resistance, treatment failure rates are high, which allows this opportunistic pathogen to thrive during infection in immune-compromised patients. can cause infections within a broad range of host niches, with pneumonia and bacteraemia being associated with the greatest levels of morbidity and mortality. Although its resistance to antibiotics is widely studied, our understanding of the mechanisms required for dealing with environmental stresses related to virulence and hospital persistence, such as copper toxicity, is limited. Here, we performed an in silico analysis of the copper resistome, examining its regulation under copper stress. Using comparative analyses of bacterial P-type ATPases, we propose that encodes a member of a novel subgroup of P ATPases. Analyses of three putative inner membrane copper efflux systems identified the P ATPase CopA as the primary mediator of cytoplasmic copper resistance in . Using a murine model of pneumonia, we reveal that CopA contributes to the virulence of . Collectively, this study advances our understanding of how deals with environmental copper toxicity, and it provides novel insights into how combats adversities encountered as part of the host immune defence.
已经成为医院感染的主要病原体之一。由于其内在和适应性的抗生素耐药性水平很高，治疗失败率很高，这使得这种机会性病原体在免疫功能低下的患者感染期间得以繁衍生息。可以在广泛的宿主小生境中引起感染，肺炎和菌血症与发病率和死亡率的最高水平相关。尽管它对抗生素的耐药性得到了广泛的研究，但我们对与毒力和医院持久性相关的环境应激（如铜毒性）有关的应对机制的理解是有限的。在这里，我们对 的铜抗性组进行了计算机分析，研究了其在铜胁迫下的调控。通过对细菌 P 型 ATP 酶的比较分析，我们提出 编码了一种新型 P ATPase 亚群的成员。对三种推测的内膜铜外排系统的分析表明，CopA 是 细胞质铜抗性的主要调节剂。使用 肺炎的小鼠模型，我们揭示了 CopA 有助于 的毒力。总的来说，这项研究增进了我们对 如何应对环境铜毒性的理解，并为 如何应对宿主免疫防御过程中遇到的逆境提供了新的见解。
