摘要

肺炎克雷伯氏菌是全球多重耐药性感染的重要原因。最近的研究强调了多重耐药的肺炎克雷伯菌菌株的出现，它表现出对mgrB调节基因的突变失活引起的粘菌素（一种最后一种抗生素）的抗性。然而，mgrB相关粘菌素抗性的精确分子抗性机制及其对毒力的影响仍不清楚。在这里，我们构建了mgrB基因肺炎克雷伯菌突变体，并对其脂质A结构，多粘菌素和抗菌肽抗性，感染后的毒力和炎症反应进行了表征。我们的数据显示，mgrB突变诱导PhoPQ控制的脂质A重塑，其不仅赋予多粘菌素抗性，还通过降低抗微生物肽易感性并减弱早期宿主防御反应激活而增强肺炎克雷伯菌毒力。总体而言，我们的研究结果对患者管理和抗菌药物管理具有重要意义，同时也强调抗生素耐药性的发展并不是无情地与细菌的适应性和毒力联系在一起。

Klebsiella pneumoniae is an important cause of multidrug‐resistant infections worldwide. Recent studies highlight the emergence of multidrug‐resistantK. pneumoniae strains which show resistance to colistin, a last‐line antibiotic, arising from mutational inactivation of the mgrB regulatory gene. However, the precise molecular resistance mechanisms of mgrB‐associated colistin resistance and its impact on virulence remain unclear. Here, we constructed an mgrB gene K. pneumoniaemutant and performed characterisation of its lipid A structure, polymyxin and antimicrobial peptide resistance, virulence and inflammatory responses upon infection. Our data reveal that mgrB mutation induces PhoPQ‐governed lipid A remodelling which confers not only resistance to polymyxins, but also enhances K. pneumoniae virulence by decreasing antimicrobial peptide susceptibility and attenuating early host defence response activation. Overall, our findings have important implications for patient management and antimicrobial stewardship, while also stressing antibiotic resistance development is not inexorably linked with subdued bacterial fitness and virulence.

http://embomolmed.embopress.org/content/early/2017/02/15/emmm.201607336