Efflux Pump Inhibitors in Controlling Antibiotic Resistance: Outlook under a Heavy Metal Contamination Context
Thi Huyen Thu Nguyen,
Hai Dang Nguyen,
Mai Huong Le,
Thi Thu Hien Nguyen,
Thi Dua Nguyen,
Duc Long Nguyen,
Quang Huy Nguyen,
Thi Kieu Oanh Nguyen,
Serge Michalet,
Marie-Geneviève Dijoux-Franca,
Hoang Nam Pham
Affiliations
Thi Huyen Thu Nguyen
Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam
Hai Dang Nguyen
Department of Academic Affairs, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam
Mai Huong Le
Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 1H Building, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam
Thi Thu Hien Nguyen
Institute of Biological and Food Technology, Hanoi Open University, 101B Nguyen Hien, Hanoi 11615, Vietnam
Thi Dua Nguyen
Saint Paul Hospital, 12 Chu Van An, Hanoi 11114, Vietnam
Duc Long Nguyen
Saint Paul Hospital, 12 Chu Van An, Hanoi 11114, Vietnam
Quang Huy Nguyen
Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam
Thi Kieu Oanh Nguyen
Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam
Serge Michalet
UMR 5557, Ecologie Microbienne, CNRS, INRAe, VetagroSup, UCBL, Université de Lyon, 43 Boulevard du 11 Novembre, F-69622 Villeurbanne, France
Marie-Geneviève Dijoux-Franca
UMR 5557, Ecologie Microbienne, CNRS, INRAe, VetagroSup, UCBL, Université de Lyon, 43 Boulevard du 11 Novembre, F-69622 Villeurbanne, France
Hoang Nam Pham
Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam
Multi-drug resistance to antibiotics represents a growing challenge in treating infectious diseases. Outside the hospital, bacteria with the multi-drug resistance (MDR) phenotype have an increased prevalence in anthropized environments, thus implying that chemical stresses, such as metals, hydrocarbons, organic compounds, etc., are the source of such resistance. There is a developing hypothesis regarding the role of metal contamination in terrestrial and aquatic environments as a selective agent in the proliferation of antibiotic resistance caused by the co-selection of antibiotic and metal resistance genes carried by transmissible plasmids and/or associated with transposons. Efflux pumps are also known to be involved in either antibiotic or metal resistance. In order to deal with these situations, microorganisms use an effective strategy that includes a range of expressions based on biochemical and genetic mechanisms. The data from numerous studies suggest that heavy metal contamination could affect the dissemination of antibiotic-resistant genes. Environmental pollution caused by anthropogenic activities could lead to mutagenesis based on the synergy between antibiotic efficacy and the acquired resistance mechanism under stressors. Moreover, the acquired resistance includes plasmid-encoded specific efflux pumps. Soil microbiomes have been reported as reservoirs of resistance genes that are available for exchange with pathogenic bacteria. Importantly, metal-contaminated soil is a selective agent that proliferates antibiotic resistance through efflux pumps. Thus, the use of multi-drug efflux pump inhibitors (EPIs) originating from natural plants or synthetic compounds is a promising approach for restoring the efficacy of existing antibiotics, even though they face a lot of challenges.
