engleski

Proteomic response of β-lactamases-producing Enterobacter cloacae complex strain to cefotaxime-induced stress

Bacteria of the Enterobacter cloacae complex are among the ten most common pathogens causing nosocomial infections in the USA. Consequently, increased resistance to β-lactam antibiotics, particularly expanded-spectrum cephalosporins like cefotaxime (CTX), poses a serious threat. Differential In-Gel Electrophoresis (DIGE), followed by LC-MS/MS analysis and bioinformatics tools, was employed to investigate the survival mechanisms of a multidrug-resistant E. hormaechei subsp. steigerwaltii 51 carrying several β- lactamase- encoding genes, including the ‘pandemic’ blaCTX-M-15. After exposing the strain with sub-minimal inhibitory concentration (MIC) of CTX, a total of 1072 spots from the whole-cell proteome were detected, out of which 35 were differentially expressed (P ≤ 0.05, fold change ≥1.5). Almost 50% of these proteins were involved in cell metabolism and energy production, and then cell wall organization/virulence, stress response and transport. This is the first study investigating the whole-cell proteomic response related to the survival of β-lactamases- producing strain, belonging to the E. cloacae complex when exposed to β-lactam antibiotic. Our data support the theory of a multifactorial synergistic effect of diverse proteomic changes occurring in bacterial cells during antibiotic exposure, depicting the complexity of β-lactam resistance and giving us an insight in the key pathways mediating the antibiotic resistance in this emerging opportunistic pathogen.

Enterobacter cloacae complex ; Enterobacter hormaechei ; CTX-M-15 ; β-lactamase ; Proteomics ; 2D-DIGE

This work was supported by the Mediterranean Institute for Life Sciences (Nelia and Amadeo Barletta Foundation, NAOS Group) to FAM and SC, and Ministry of Science, Education and Sports of Republic of Croatia to AM.