Abstract

Antibiotic resistance is an emerging public health issue. Plasmids are one of the popular carriers to disseminate resistance genes among pathogens. However, the response of plasmid-carrying bacteria to antibiotic treatment and how these bacteria evolve to increase their resistance remain elusive. In this study, we conjugated plasmid pNDM-HK to E. coli J53 recipient cells and selected survivors using different concentrations of the broad spectrum antibiotic meropenem. After selection, transconjugants conferred varying minimum inhibitory concentrations with respect to carbapenems. We sequenced and compared the transcriptomes of transconjugants that exhibited distinct carbapenem susceptibilities, and found that the loss of outer membrane proteins led to antibiotic resistance. Moreover, we identified a novel mutation, G63S, in transcription factor OmpR which moderates the expression of outer membrane proteins. The loss of porins was due to incapability of phosphorylation, which is essential for porin transcription and carbapenem resistance. We also characterized other genes that are regulated by ompR in this mutant, which contributed to bacterial antibiotic resistance. Overall, our studies suggest antibiotic pressure after conjugation might be an alternative pathway to promote antimicrobial resistance.

Details

Title
Fine-tuning carbapenem resistance by reducing porin permeability of bacteria activated in the selection process of conjugation
Author
Hoi-Kuan Kong 1 ; Pan, Qing 1 ; Wai-U Lo 2 ; Liu, Xuan 1 ; Law, Carmen O K 1 ; Ting-fung, Chan 3   VIAFID ORCID Logo  ; Pak-Leung, Ho 2 ; Terrence Chi-Kong Lau 1   VIAFID ORCID Logo 

 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong Special Administrative Region, Kowloon Tong, People’s Republic of China 
 Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Kowloon Tong, People’s Republic of China 
 School of Life Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, Kowloon Tong, People’s Republic of China 
Pages
1-11
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2120167728
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.