Zilan Wei, Jie Xu, Jiahui Wu, Youliang Wang, Shuiping Chen
{"title":"Phenotypic Profiling of Tigecycline-resistant Klebsiella pneumoniae Strains Induced In vitro.","authors":"Zilan Wei, Jie Xu, Jiahui Wu, Youliang Wang, Shuiping Chen","doi":"10.1007/s00284-024-04018-8","DOIUrl":null,"url":null,"abstract":"<p><p>Tigecycline is one of the last-resort treatment options for infections caused by carbapenem-resistant Klebsiella pneumoniae (KP). Unfortunately, tigecycline resistance is increasingly reported and causes an unprecedented public health crisis worldwide. Although studies on tigecycline resistance are expanding, the underlying mechanisms are not fully understood. The goal of this study is to investigate resistance-associated phenotypic changes in descendant tigecycline-resistant KP strains induced in vitro. Compared with the parental KP strains, descendant tigecycline-resistant strains grew slowly and reversed the susceptibility of carbapenems and aminoglycosides from resistance to sensitivity. The efflux pump inhibitor phenylalanyl-arginyl-β-naphthylamine (PAβN) could significantly decrease the MIC values of tigecycline in descendant strains, but the efflux pump inhibitor carbonyl cyanide-m-chlorophenylhydrazine (CCCP), verapamil, and reserpine could not. Although the descendant strains showed inconsistent (increased or decreased) biofilm formation and ethidium bromide uptake, they showed consistently decreased ethidium bromide efflux. As for the expression of efflux pumps and regulators determined by quantitative reverse transcript polymerase chain reaction (qRT-PCR), higher level of efflux pump acrAB-TolC and lower level of regulator ramA were observed in these descendant strains, while the efflux pump oqxAB and the other 6 regulators (acrR, rarA, marA, soxS, bpeT, and Rob) showed inconsistent (higher or lower) expression level. Thus, a global regulatory network driven by regulators (acrR, ramA, rarA, marA, soxS, bpeT, rob, etc.) alone or synergistically might play important roles in conferring tigecycline resistance in KP by regulation of efflux pumps (especially increasing acrAB-TolC) or other pathways.</p>","PeriodicalId":11360,"journal":{"name":"Current Microbiology","volume":"82 1","pages":"37"},"PeriodicalIF":2.3000,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s00284-024-04018-8","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Phenotypic Profiling of Tigecycline-resistant Klebsiella pneumoniae Strains Induced In vitro.
Tigecycline is one of the last-resort treatment options for infections caused by carbapenem-resistant Klebsiella pneumoniae (KP). Unfortunately, tigecycline resistance is increasingly reported and causes an unprecedented public health crisis worldwide. Although studies on tigecycline resistance are expanding, the underlying mechanisms are not fully understood. The goal of this study is to investigate resistance-associated phenotypic changes in descendant tigecycline-resistant KP strains induced in vitro. Compared with the parental KP strains, descendant tigecycline-resistant strains grew slowly and reversed the susceptibility of carbapenems and aminoglycosides from resistance to sensitivity. The efflux pump inhibitor phenylalanyl-arginyl-β-naphthylamine (PAβN) could significantly decrease the MIC values of tigecycline in descendant strains, but the efflux pump inhibitor carbonyl cyanide-m-chlorophenylhydrazine (CCCP), verapamil, and reserpine could not. Although the descendant strains showed inconsistent (increased or decreased) biofilm formation and ethidium bromide uptake, they showed consistently decreased ethidium bromide efflux. As for the expression of efflux pumps and regulators determined by quantitative reverse transcript polymerase chain reaction (qRT-PCR), higher level of efflux pump acrAB-TolC and lower level of regulator ramA were observed in these descendant strains, while the efflux pump oqxAB and the other 6 regulators (acrR, rarA, marA, soxS, bpeT, and Rob) showed inconsistent (higher or lower) expression level. Thus, a global regulatory network driven by regulators (acrR, ramA, rarA, marA, soxS, bpeT, rob, etc.) alone or synergistically might play important roles in conferring tigecycline resistance in KP by regulation of efflux pumps (especially increasing acrAB-TolC) or other pathways.
期刊介绍:
Current Microbiology is a well-established journal that publishes articles in all aspects of microbial cells and the interactions between the microorganisms, their hosts and the environment.
Current Microbiology publishes original research articles, short communications, reviews and letters to the editor, spanning the following areas:
physiology, biochemistry, genetics, genomics, biotechnology, ecology, evolution, morphology, taxonomy, diagnostic methods, medical and clinical microbiology and immunology as applied to microorganisms.