Mutagenic effects of pesticides on Enteric Bacteria and their role in the rise of antimicrobial resistance (AMR)

Abstract

Microbial antibiotic resistance threatens world health dangerously. Moreover the non-antibiotic stressors have also contributed to bacterial antibiotic resistance. Pesticides affect bacterial antibiotic resistance, and this study seeks to understand the process. Efflux pumps has been activated by pesticide stress and induces antibiotic-resistant gene alterations in bacteria. Pesticides increase cell membrane permeability and bacterial mobile gene elements, which increases antibiotic resistance gene transmission. Despite multiple studies linking mutagenic effect of pesticides on enteric bacteria, a comprehensive review is lacking. For this study a systematic search was performed using four databases (PubMed, Scopus, Web of Science and Embase) and one search engine (Google Scholar) for original studies (From February 2022 to April 2023). Later, between July 2022 and August 2023, the findings were cross-checked and updated the existing literature. As per our eligible criteria, overall 101 studies were selected for the analysis. Throughout this study 471 pesticide chemicals have been identified from 101 publications, and a significant portion of them are mutagenic to Salmonella typhimurium, Escherichia coli, and Bacillus subtilis. Many pesticide mutagenicity investigations use Salmonella as the main testing strain. Studies have found that Salmonella strains TA100, TA98, and TA1535 are used most often, with E. coli strain WP2 seldom used. The Ames test is usually considered a reliable mutagenicity test. Mutagenic doses vary with organism and strain spanning from the range of 0.1 ml/plate to 5000 μg/plate. Acephate (0.1 μg/plate), Allethrin (2000 μg/plate, 1500 μg/plate, 0.1 μg/plate), Demond EC 25 (400 and 800 μg/plate), Dicrotophos (5000 μg/plate), and Lambda-cyhalothrin (5, 10 μmol/plate, 0.5, 1, 2.5, 5, and 10 μmol/plate) are some of the insecticidal compounds that mutate S. Typhimurium strains at different doses. Moreover, dichlorvos showing mutagenicity on E. coli at 0.1 ml/plate doses and Dibrom showing mutagenicity on B. subtilis at 50,100 and 300 μg/plate. Similarly, some of the fungicidal compounds like Thiram, TBZ, NNN, Folpet showing mutagenicity on different organisms at different doses. The doses are (0.05 and 0.5 mg/plate, 0.01, and 0.1 mg/well, 200μg/plate, 50 μg/plate, 50 μg/plate, 1 μg/plate), respectively. And for herbicides, HEH (2-hydrazinoethanol), Roundup, Triallate poses mutagenicity on different organism at 0.1ml/plate, 720 μg/ plate and 50, 100, and 300 μg/plate, respectively. Most concerning is the study's link between mutagenic chemicals and human and animal food samples. The US Food and Drug Administration found pendimethalin, a moderately hazardous herbicide, in animal and human food samples. Additionally, the food samples contain high levels of dichlorvos, carbofuran, and monocrotophos, which are harmful to human health. Heptachlor, an outdated vi insecticide, was found in food samples. This comprehensive study shows the mutagenic effects of pesticides that encompasses total 23% of the compounds that showing mutagenicity. Among them insecticides showing mutagenicity 96.67 % (58 out of 60) in S. Typhimurium, along with 50% on E. coli (30 out of 60) and 1.67% on B. subtilis (1 out of 60). Out of 26 mutagenic compounds, fungicides showing mutagenicity on S. Typhimurium, E. coli and B. subtilis at 96.15%, 34.61% and 7.7%, respectively. For herbicide out of 20 mutagenic compounds 20 (100%) shows mutagenicity for S. Typhimurium, 2 of them (10%) shows mutagenicity on E. coli and one of them (5%) shows mutagenicity on B. subtilis. These mutagenic pesticides have also been found in human and animal food samples. Overall exposure and mutagenic impacts of the pesticides could generate a potential links to raise antibiotic-resistant microorganisms.