engleski

Proteomic analysis of a multidrug-resistant and β-lactamases-producing environmental strain of Enterobacter cloacae complex

The continuous emergence of antibiotic- resistant pathogens seriously threatens the effectiveness of antimicrobial treatment leading to increased morbidity, mortality and healthcare expenditure worldwide, and according to WHO "is about to become a public health emergency of yet unknown proportions". Among many mechanisms by which bacteria render ineffective almost all antibiotic families currently in use, one of the most important is the resistance of Gram-negative bacilli to extended-spectrum β-lactam antibiotics, like cefotaxime (CTX). Enterobacter hormaechei, a member of Enterobacter cloacae complex and a part of human endogenous flora, has now become clinically significant as emerging nosocomial pathogen associated with septicaemia outbreaks. E. hormaechei strain 51, isolated in 2012 from seawater, showed multidrug resistant phenotype including resistance to CTX as a result of simultaneous production of several β- lactamases. To understand the mechanisms involved in CTX induced stress response, Differential In-Gel Electrophoresis (DIGE) followed by LC-MS/MS analysis and bioinformatics, was employed to investigate protein changes of this resistant strain when challenged with sub-MIC of CTX. Total of 1072 protein spots were detected, out of which 35 were differentially expressed (p-value ≤0.05, max fold change ≥1.5). Protein expression changes at different subcellular levels were detected in CTX-resistant strain when exposed to antibiotic stress. In this aspect, coherent genomic and proteomic approaches might help us understand the specific traits associated with persistence of antibiotic-resistant strains in order to gain control over further spread of antibiotic resistance and possibly even uncover the drug resistance-associated proteins that could serve as novel drug targets.

Proteomics; DIGE; beta-lactamase; Enterobacter cloacae

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