Overcoming addition of phosphoethanolamine to lipid A mediated colistin resistance in Acinetobacter baumannii clinical isolates with colistin-sulbactam combination therapy

使用粘菌素-舒巴坦联合疗法克服鲍曼不动杆菌临床分离株中脂质 A 中添加磷酸乙醇胺介导的粘菌素耐药性

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作者:Sukrit Srisakul #, Dhammika Leshan Wannigama, Paul G Higgins #, Cameron Hurst #, Shuichi Abe, Parichart Hongsing #, Thammakorn Saethang, Sirirat Luk-In #, Tingting Liao, Naris Kueakulpattana, Aye Mya Sithu Shein, Lin Gan, Rosalyn Kupwiwat, Chanikan Tanasatitchai, Pattama Wapeesittipan, Phatthranit P

Abstract

Overcoming colistin-resistant Acinetobacter baumannii (CoR-AB) has become a major concern due to the lack of effective antibiotics. This study aimed to explore the prevalence of CoR-AB clinical isolates in Thailand, their mechanisms of resistance, and test the efficacy of colistin plus sulbactam against CoR-AB isolates. The colistin resistance rate among carbapenem-resistant A. baumannii was 15.14%. The mcr gene or its variants were not detected in CoR-AB isolates by PCR screening. The lipid A mass spectra of CoR-AB isolates showed the additional [M-H]- ion peak at m/z = 2034 that correlated to the phosphoethanolamine (pEtN) addition to lipid A (N = 27/30). The important amino acid substitutions were found at position S14P, A138T, A227V in PmrB that are associated with overexpression of the pEtN transferase (PmrC) and contributed the pEtN addition. The lipopolysacccharide production genes (lpxACD) were not related to lipid A mass spectra. A colistin plus sulbactam combination exhibited the synergy rate at 86.7% against CoR-AB isolates compare to sulbactam (85.89% resistance) or colistin (15.14% resistance) alone. The excellent synergistic activity of colistin plus sulbactam combination has the potential for the treatment of CoR-AB infections.

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