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Use of a combined antibacterial synergy approach and the ANNOgesic tool to identify novel targets within the gene networks of multidrug-resistant Klebsiella pneumoniae

Authors
 Hyunsook Lee  ;  Sung-Huan Yu  ;  Jung Eun Shim  ;  Dongeun Yong 
Citation
 MSYSTEMS, Vol.9(3) : e0087723, 2024-03 
Journal Title
MSYSTEMS
Issue Date
2024-03
MeSH
Animals ; Anti-Bacterial Agents / pharmacology ; Colistin / metabolism ; Gene Regulatory Networks / genetics ; Humans ; Klebsiella pneumoniae* / genetics ; Riboswitch*
Keywords
ANNOgesic ; RNA sequencing ; chemical compound ; colistin ; gene network ; meropenem ; multidrug-resistant (MDR) ; noncoding RNA ; synergy
Abstract
Since the 1980s, the development of new drug classes for the treatment of multidrug-resistant Klebsiella pneumoniae has become limited, highlighting the urgent need for novel antibiotics. To address this challenge, this study aimed to explore the synergistic interactions between chemical compounds and representative antibiotics, such as carbapenem and colistin. The primary objective of this study was not only to mitigate the adverse impact of multidrug-resistant K. pneumoniae on public health but also to establish a sustainable balance among humans, animals, and the environment. Phenotypical measurements were conducted using the broth microdilution technique to determine the drug sensitivity of bacterial strains. Additionally, a genotypical approach was employed, involving traditional RNA sequencing analysis to identify differentially expressed genes and the computational ANNOgesic tool to detect noncoding RNAs. This study revealed the existence of various pathways and regulatory RNA elements that form a functional network. These pathways, characterized by the expression of specific genes, contribute to the combined treatment effect and bacterial survival strategies. The connections between pathways are facilitated by regulatory RNA elements that respond to environmental changes. These findings suggest an adaptive response of bacteria to harsh environmental conditions. Copyright © 2024 Lee et al.
Files in This Item:
T202402428.pdf Download
DOI
10.1128/msystems.00877-23
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Yong, Dong Eun(용동은) ORCID logo https://orcid.org/0000-0002-1225-8477
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/199142
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