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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Infectious Agents and Disease
Volume 16 - 2025 |
doi: 10.3389/fmicb.2025.1531739
This article is part of the Research Topic Women in Infectious Agents and Disease: 2024 View all 5 articles
An integrated proteo-transcriptomics approach reveals novel drug targets against multidrug resistant Escherichia coli
Provisionally accepted- 1 University of Delhi, New Delhi, India
- 2 Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka, India
Infections due to multidrug-resistant (MDR) Escherichia coli are associated with severe morbidity and mortality, worldwide. Microbial drug resistance is a complex phenomenon which is conditioned by an interplay of several genomic, transcriptomic and proteomic factors. Here, we have conducted an integrated transcriptomics and proteomics analysis of MDR E. coli to identify genes which are differentially expressed at both mRNA and protein levels. Using RNA-Seq and SWATH-LC MS/MS it was discerned that 763 genes/proteins exhibited differential expression. Of these, 52 genes showed concordance in differential expression at both mRNA and protein levels with 41 genes exhibiting overexpression and 11 genes exhibiting under expression. Bioinformatic analysis using GO-terms, COG and KEGG functional annotations revealed that the concordantly overexpressed genes of MDR E. coli were involved primarily in biosynthesis of secondary metabolites, aminoacyl-tRNAs and ribosomes. Protein-protein interaction (PPI) network analysis of the concordantly overexpressed genes revealed 81 PPI networks and 10 hub proteins. The hub proteins (rpsI, aspS, valS, lysS, accC, topA, rpmG, rpsR, lysU and spmB) were found to be involved in aminoacylation of tRNA and lysyl-tRNA and, translation. Further, it was discerned that three hub proteins -smpB, rpsR and topA were non homologous to human proteins and were involved in several biological pathways directly and/or indirectly related to antibiotic stress. Also, absence of homology ensures a little cross-reactivity of their inhibitors/drugs with human proteins and undesirable side effects. Thus, these proteins might be explored as novel drug targets against both drug-resistant and -sensitive populations of E. coli.
Keywords: RNA-Seq, SWATH-LC MS/MS, protein-protein interactions, multidrug resistance, drug target
Received: 20 Nov 2024; Accepted: 22 Jan 2025.
Copyright: © 2025 Aswal, Singh, Singhal and Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Neelja Singhal, University of Delhi, New Delhi, India
Manish Kumar, University of Delhi, New Delhi, India
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