The use of SWATH to analyse the dynamic changes of bacterial proteome of carbapanemase-producing Escherichia coli under antibiotic pressure

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Sidjabat, Hanna E
Gien, Jolene
Kvaskoff, David
Ashman, Keith
Vaswani, Kanchan
Reed, Sarah
McGeary, Ross P
Paterson, David L
Bordin, Amanda
Schenk, Gerhard
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2018
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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.

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Scientific Reports

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8

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1

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© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Biochemistry and cell biology

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Sidjabat, HE; Gien, J; Kvaskoff, D; Ashman, K; Vaswani, K; Reed, S; McGeary, RP; Paterson, DL; Bordin, A; Schenk, G, The use of SWATH to analyse the dynamic changes of bacterial proteome of carbapanemase-producing Escherichia coli under antibiotic pressure, Scientific Reports, 2018, 8 (1), pp. 3871:1-3871:11

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