A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence.
A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence.
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DOI：
10.15252/emmm.201607336
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发表时间：
2017-04
影响因子：
11.1
通讯作者：
Bengoechea JA
中科院分区：
文献类型：
--
作者：
Kidd TJ;Mills G;Sá-Pessoa J;Dumigan A;Frank CG;Insua JL;Ingram R;Hobley L;Bengoechea JA
肺炎克雷伯菌是全球多重耐药感染的重要原因。最近的研究强调了多重耐药肺炎克雷伯菌菌株的出现，这些菌株对粘菌素（一种最后一线抗生素）具有耐药性，这是由mgrB调控基因的突变失活引起的。然而，mgrB相关粘菌素耐药的精确分子耐药机制及其对毒力的影响仍不清楚。在这里，我们构建了一个mgrB基因肺炎克雷伯氏菌突变体，并进行了表征其脂质A结构，多粘菌素和抗菌肽的耐药性，毒力和感染后的炎症反应。我们的数据表明，mgrB突变会诱导PhoPQ控制的脂质A重塑，这不仅赋予对多粘菌素的耐药性，还增强K。通过降低抗微生物肽的敏感性和减弱早期宿主防御反应的激活来降低肺炎克雷伯氏菌的毒力。总的来说，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与细菌适应性和毒力的减弱并不必然相关。
Klebsiella pneumoniae is an important cause of multidrug‐resistant infections worldwide. Recent studies highlight the emergence of multidrug‐resistant K. 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. pneumoniae mutant 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.