Genomic and Functional Characterization of Multidrug-Resistant <i>E. coli</i>: Insights into Resistome, Virulome, and Signaling Systems
<b>Introduction:</b> Genetic plasticity and adaptive camouflage in critical pathogens have contributed to the global surge in multidrug-resistant (MDR) infections, posing a serious threat to public health and therapeutic efficacy. Antimicrobial resistance, now a leading cause of global m...
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| Format: | Article |
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2025-06-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/14/7/667 |
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| author | Vijaya Bharathi Srinivasan Naveenraj Rajasekar Karthikeyan Krishnan Mahesh Kumar Chankit Giri Balvinder Singh Govindan Rajamohan |
| author_facet | Vijaya Bharathi Srinivasan Naveenraj Rajasekar Karthikeyan Krishnan Mahesh Kumar Chankit Giri Balvinder Singh Govindan Rajamohan |
| author_sort | Vijaya Bharathi Srinivasan |
| collection | DOAJ |
| description | <b>Introduction:</b> Genetic plasticity and adaptive camouflage in critical pathogens have contributed to the global surge in multidrug-resistant (MDR) infections, posing a serious threat to public health and therapeutic efficacy. Antimicrobial resistance, now a leading cause of global mortality, demands urgent action through diagnostics, vaccines, and therapeutics. In India, the Indian Council of Medical Research’s surveillance network identifies <i>Escherichia coli</i> as a major cause of urinary tract infections, with increasing prevalence in human gut microbiomes, highlighting its significance across One Health domains. <b>Methods:</b> Whole-genome sequencing of <i>E. coli</i> strain ECG015, isolated from a human gut sample, was performed using the Illumina NextSeq platform. <b>Results:</b> Genomic analysis revealed multiple antibiotic resistance genes, virulence factors, and efflux pump components. Phylogenomic comparisons showed close relatedness to pathovars from both human and animal origins. Notably the genome encoded protein tyrosine kinases (Etk/Ptk and Wzc) and displayed variations in the envelope stress-responsive CpxAR two-component system. Promoter analysis identified putative CpxR-binding sites upstream of genes involved in resistance, efflux, protein kinases, and the MazEF toxin–antitoxin module, suggesting a potential regulatory role of CpxAR in stress response and persistence. <b>Conclusions:</b> This study presents a comprehensive genomic profile of <i>E</i>. <i>coli</i> ECG015, a gut-derived isolate exhibiting clinically significant resistance traits. For the first time, it implicates the CpxAR two-component system as a potential central regulator coordinating antimicrobial resistance, stress kinase signaling, and programmed cell death. These findings lay the groundwork for future functional studies aimed at targeting stress-response pathways as novel intervention strategies against antimicrobial resistance. |
| format | Article |
| id | doaj-art-c250067d811442809d4f3a8932c8ee5e |
| institution | DOAJ |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj-art-c250067d811442809d4f3a8932c8ee5e2025-08-20T02:45:52ZengMDPI AGAntibiotics2079-63822025-06-0114766710.3390/antibiotics14070667Genomic and Functional Characterization of Multidrug-Resistant <i>E. coli</i>: Insights into Resistome, Virulome, and Signaling SystemsVijaya Bharathi Srinivasan0Naveenraj Rajasekar1Karthikeyan Krishnan2Mahesh Kumar3Chankit Giri4Balvinder Singh5Govindan Rajamohan6CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, IndiaCSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, IndiaCSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, IndiaCSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, IndiaCSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, IndiaCSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, IndiaCSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India<b>Introduction:</b> Genetic plasticity and adaptive camouflage in critical pathogens have contributed to the global surge in multidrug-resistant (MDR) infections, posing a serious threat to public health and therapeutic efficacy. Antimicrobial resistance, now a leading cause of global mortality, demands urgent action through diagnostics, vaccines, and therapeutics. In India, the Indian Council of Medical Research’s surveillance network identifies <i>Escherichia coli</i> as a major cause of urinary tract infections, with increasing prevalence in human gut microbiomes, highlighting its significance across One Health domains. <b>Methods:</b> Whole-genome sequencing of <i>E. coli</i> strain ECG015, isolated from a human gut sample, was performed using the Illumina NextSeq platform. <b>Results:</b> Genomic analysis revealed multiple antibiotic resistance genes, virulence factors, and efflux pump components. Phylogenomic comparisons showed close relatedness to pathovars from both human and animal origins. Notably the genome encoded protein tyrosine kinases (Etk/Ptk and Wzc) and displayed variations in the envelope stress-responsive CpxAR two-component system. Promoter analysis identified putative CpxR-binding sites upstream of genes involved in resistance, efflux, protein kinases, and the MazEF toxin–antitoxin module, suggesting a potential regulatory role of CpxAR in stress response and persistence. <b>Conclusions:</b> This study presents a comprehensive genomic profile of <i>E</i>. <i>coli</i> ECG015, a gut-derived isolate exhibiting clinically significant resistance traits. For the first time, it implicates the CpxAR two-component system as a potential central regulator coordinating antimicrobial resistance, stress kinase signaling, and programmed cell death. These findings lay the groundwork for future functional studies aimed at targeting stress-response pathways as novel intervention strategies against antimicrobial resistance.https://www.mdpi.com/2079-6382/14/7/667WHO critical threat<i>E. coli</i>antimicrobial resistanceOne HealthCpxAR signalingprotein kinases |
| spellingShingle | Vijaya Bharathi Srinivasan Naveenraj Rajasekar Karthikeyan Krishnan Mahesh Kumar Chankit Giri Balvinder Singh Govindan Rajamohan Genomic and Functional Characterization of Multidrug-Resistant <i>E. coli</i>: Insights into Resistome, Virulome, and Signaling Systems Antibiotics WHO critical threat <i>E. coli</i> antimicrobial resistance One Health CpxAR signaling protein kinases |
| title | Genomic and Functional Characterization of Multidrug-Resistant <i>E. coli</i>: Insights into Resistome, Virulome, and Signaling Systems |
| title_full | Genomic and Functional Characterization of Multidrug-Resistant <i>E. coli</i>: Insights into Resistome, Virulome, and Signaling Systems |
| title_fullStr | Genomic and Functional Characterization of Multidrug-Resistant <i>E. coli</i>: Insights into Resistome, Virulome, and Signaling Systems |
| title_full_unstemmed | Genomic and Functional Characterization of Multidrug-Resistant <i>E. coli</i>: Insights into Resistome, Virulome, and Signaling Systems |
| title_short | Genomic and Functional Characterization of Multidrug-Resistant <i>E. coli</i>: Insights into Resistome, Virulome, and Signaling Systems |
| title_sort | genomic and functional characterization of multidrug resistant i e coli i insights into resistome virulome and signaling systems |
| topic | WHO critical threat <i>E. coli</i> antimicrobial resistance One Health CpxAR signaling protein kinases |
| url | https://www.mdpi.com/2079-6382/14/7/667 |
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