Abstract
Antibiotic resistance associated with the clinically significant carbapenemases KPC, NDM and OXA-48 in Enterobacteriaceae is emerging as worldwide. In Australia, IMP-producing Enterobacteriaceae are the most prevalent carbapenemase-producing Enterobacteriaceae (CPE). Genomic characteristics of such CPE are well described, but the corresponding proteome is poorly characterised. We have thus developed a method to analyse dynamic changes in the proteome of CPE under antibiotic pressure. Specifically, we have investigated the effect of meropenem at sub-lethal concentrations to develop a better understanding of how antibiotic pressure leads to resistance. Escherichia coli strains producing either NDM-, IMP- or KPC-type carbapenemases were included in this study, and their proteomes were analysed in growth conditions with or without meropenem. The most significant difference in the bacterial proteomes upon the addition of meropenem was triggered amongst NDM-producers and to a lower extent amongst KPC-producers. In particular, HU DNA-binding proteins, the GroEL/GroES chaperonin complex and GrpE proteins were overexpressed. These proteins may thus contribute to the better adaptability of NDM- and KPC-producers to meropenem. A significant meropenem-induced increase in the expression of the outer membrane protein A was only observed in IMP-producers, thus demonstrating that carbapenemase-mediated resistance relies on far more complex mechanisms than simple inactivation of the antibiotic.
Highlights
Resistance to antimicrobial agents has been increasing among Enterobacteriaceae, to the point where resistance to multiple antibiotic classes is not uncommon
Quinolones are powerful broad-spectrum antimicrobials used for the treatment of a wide variety of community-acquired and nosocomial infections[35]
The most common mechanism of resistance to quinolones in E. coli includes alterations in genes located in the quinolone-resistance-determining region (QRDR) and that encode subunits of the quinolone targets, i.e. DNA gyrase and topoisomerase IV22
Summary
Resistance to antimicrobial agents has been increasing among Enterobacteriaceae, to the point where resistance to multiple antibiotic classes is not uncommon One such class is the quinolones, broad-spectrum antimicrobial agents used to treat various bacterial infections, but resistance against these compounds has increased in the clinical field[1]. The primary mechanisms of carbapenem resistance in Enterobacteriaceae is the acquisition of carbapenemase-encoding genes e.g. blaKPC, blaIMP , blaNDM and blaOXA-48-like[3]. These carbapenemases are a large group of enzymes that catalyse the hydrolytic opening of the four-membered ring characteristic for β-lactam antibiotics such as carbapenems or cephalosporins and penicillins. Class A carbapenemases, such as Klebsiella pneumoniae carbapenemase (KPC), require a serine residue www.nature.com/scientificreports/
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
