Gut colonization with antibiotic-resistant Escherichia coli pathobionts leads to disease severity in ulcerative colitis

• Published in: International journal of antimicrobial agents Vol. 64; no. 4; p. 107289
• Main Authors: Yadav, Asha, Shinde, Pratik Balwant, Mohan, Hari, Dhar, Mahesh S., Ponnusamy, Kalaiarasan, Marwal, Robin, Radhakrishnan, V.S., Goyal, Sandeep, Kedia, Saurabh, Ahuja, Vineet, Sharma, Krishna Kant
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2024
• Subjects: Escherichia coli; Multi-drug resistance; Multi-omics; Pathobionts; Ulcerative colitis; Multi-drug resistance; Pathobionts; Escherichia coli; Multi-omics; Ulcerative colitis
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2024.107289

•Accumulation of antimicrobial resistance (AMR) genes in human meta-gut resistome.•Higher predominance of AMR genes in a rural population.•Higher prevalence of drug-resistant Escherichia coli in ulcerative colitis.•Antibiotic efflux proteins signify mechanism of drug resistance.•Higher prevalence of resistance against β-lactam group of antibiotics. Escherichia coli is a Gram-negative commensal of human gut. Surprisingly, the role of E. coli in the pathogenesis of ulcerative colitis (UC) has not been explored until now. Human gut microbiota composition and meta-gut resistome were evaluated using metagenomics. Antibiotic susceptibility of E. coli isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of E. coli isolates was performed to gain insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology. In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy controls (HC) [518]. The metagenome study revealed a higher prevalence of AMR genes in the rural population (378 in HC; 607 in UC) compared to the urban (340 in HC; 578 in UC). Approximately, 40% of all E. coli isolates were multi-drug resistant (MDR), with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and inflammatory mediator (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut. In addition to the conventional culturomics method, a multi-omics strategy provides deeper insights into the disease etiology, emergence of MDR pathobionts, and their roles in the disruption of the healthy gut environment in UC patients. [Display omitted]