학술논문
Overcoming addition of phosphoethanolamine to lipid A mediated colistin resistance in Acinetobacter baumannii clinical isolates with colistin–sulbactam combination therapy.
Document Type
Article
Author
Srisakul, Sukrit; Wannigama, Dhammika Leshan; Higgins, Paul G.; Hurst, Cameron; Abe, Shuichi; Hongsing, Parichart; Saethang, Thammakorn; Luk-in, Sirirat; Liao, Tingting; Kueakulpattana, Naris; Shein, Aye Mya Sithu; Gan, Lin; Kupwiwat, Rosalyn; Tanasatitchai, Chanikan; Wapeesittipan, Pattama; Phattharapornjaroen, Phatthranit; Badavath, Vishnu Nayak; Leelahavanichkul, Asada; Chatsuwan, Tanittha
Source
Subject
*COLISTIN
*ACINETOBACTER baumannii
*LIPIDS
*MASS spectrometry
*GENETIC variation
*AMINO acids
*
*
*
*
*
Language
ISSN
2045-2322
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. [ABSTRACT FROM AUTHOR]