Abstract
The emergence and spread of carbapenem-resistant Klebsiella pneumoniae infections have worsened the current situation worldwide, in which totally drug-resistant strains (bad bugs) are becoming increasingly prominent. Bacterial biofilms enable bacteria to tolerate higher doses of antibiotics and other stresses, which may lead to the drug resistance. In the present study, we performed proteomics on the carbapenem-resistant NDM-4-producing K. pneumoniae clinical isolate under meropenem stress. Liquid chromatography coupled with mass spectrometry (LC–MS/MS) analysis revealed that 69 proteins were down-regulated (≤0.42-fold change) under meropenem exposure. Within the identified down-regulated proteome (69 proteins), we found a group of 13 proteins involved in flagellar, fimbriae, and pili formation and their related functions. Further, systems biology approaches were employed to reveal their networking pathways. We suggest that these down-regulated proteins and their interactive partners cumulatively contribute to the emergence of a biofilm-like state and the survival of bacteria under drug pressure, which could reveal novel mechanisms or pathways involved in drug resistance. These down-regulated proteins and their pathways might be used as targets for the development of novel therapeutics against antimicrobial-resistant (AMR) infections.
Highlights
IntroductionThe emergence and spread of drug-resistant K. pneumoniae are worsening the medical situation worldwide
Klebsiella pneumoniae is a gram-negative bacteria of the family Enterobacteriaceae
A single colony of K. pneumoniae was inoculated in Luria– Bertani (LB) broth and kept at 37◦C at 220 rpm, and a sub-minimum inhibitory concentration (MIC) (32 μg/ml) of meropenem was used for induction in a 200 ml culture flask
Summary
The emergence and spread of drug-resistant K. pneumoniae are worsening the medical situation worldwide. Carbapenems have been considered the last line of defense in the treatment of drug-resistant infections (Paterson, 2000; Paterson and Bonomo, 2005). Drug Resistance in K. pneumoniae Through Motility Proteome carbapenem during the course of treatment leads to the emergence of carbapenem-resistant infections. Carbapenemases are produced that cleave or hydrolyze the carbapenem drugs and contribute to carbapenem resistance. Carbapenemase overproduction and porin deficiency are the two major causes of carbapenem resistance (Ambler et al, 1991; MartínezMartínez et al, 1999; Jacoby et al, 2004; Loli et al, 2006). Several explanations have been put forward to explain the mechanisms of carbapenem resistance, but our information is as yet incomplete or fragmentary
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