Cefiderocol Resistance in Klebsiella pneumoniae Is Linked to SHV Extended-Spectrum β-Lactamase Activities and Functional Loss of the Outer Membrane Porin OmpK35.
Cefiderocol Resistance in Klebsiella pneumoniae Is Linked to SHV Extended-Spectrum β-Lactamase Activities and Functional Loss of the Outer Membrane Porin OmpK35.
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肺炎克雷伯菌的头孢地考耐药性与 SHV 超广谱 β-内酰胺酶活性和外膜孔蛋白 OmpK35 的功能丧失有关。
DOI：
10.1128/spectrum.03496-22
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发表时间：
2023-06-15
影响因子：
3.7
通讯作者：
Huang, En
中科院分区：
文献类型：
--
作者：
Moon, Sun Hee;Huang, En
来自CDC和FDA抗生素耐药分离株库的肺炎克雷伯菌AR 0047对头孢地罗可（一种铁载体结合的头孢菌素）具有耐药性。基因组学分析和遗传互补分析表明，ompK 35的移码突变有助于头孢地罗可耐药。blaSHV-5或blaSHV-12在大肠杆菌中的异源表达增加了宿主对头孢地罗可的抗性。此外，阿维巴坦（一种β-内酰胺酶抑制剂）可增强头孢地罗可对耐药菌株的活性。因此，头孢地罗可耐药性与SHV和ompK 35的丢失有关。重要性了解头孢地罗可耐药机制对于提供治疗感染和预防耐药性发展的解决方案至关重要。肺炎克雷伯菌AR 0047的头孢地罗克耐药性与SHV β-内酰胺酶活性和外膜孔蛋白功能丧失有关。头孢地罗可-阿维巴坦复方制剂代表了增加对头孢地罗耐药病原体效力的机会。
Klebsiella pneumoniae AR 0047 from the CDC and FDA Antibiotic Resistance Isolate Bank is resistant to cefiderocol, a siderophore-conjugated cephalosporin. Genomics analysis and genetic complementation revealed that a frameshift mutation in ompK35 contributed to cefiderocol resistance. Heterologous expression of blaSHV-5 or blaSHV-12 in Escherichia coli increased the host resistance to cefiderocol. Moreover, avibactam, a β-lactamase inhibitor, enhanced cefiderocol activity against the resistant strain. Therefore, cefiderocol resistance is linked to SHV and the loss of ompK35. IMPORTANCE Understanding cefiderocol resistance mechanisms is essential for providing solutions to treat infections and to prevent resistance development. Cefiderocol resistance in Klebsiella pneumoniae AR 0047 is linked to SHV β-lactamase activities and functional loss of outer membrane porin. The cefiderocol-avibactam combination represents an opportunity to increase potency against cefiderocol-resistant pathogens.
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