Campylobacter spp. are the leading cause of human gastroenteritis worldwide. RE-CmeABC is a newly identified resistance-enhancing multidrug efflux pump of Campylobacter spp. (C. spp.) that confers high-level resistanc...Campylobacter spp. are the leading cause of human gastroenteritis worldwide. RE-CmeABC is a newly identified resistance-enhancing multidrug efflux pump of Campylobacter spp. (C. spp.) that confers high-level resistance to fluoroquinolones, phenicols, macrolides, and tetracyclines (TETs), all of which are critical drugs in both human and veterinary medicine. In this study, we analyzed the presence and antimicrobial susceptibility of RE-cmeABC-positive Campylobacter isolates of food-animal origin from three representative regions (Shandong, Shanghai, and Guangdong) in China over three successive years, from 2014 to 2016. A total of 1088 Campylobacter isolates (931 C. coli and 157 C. jejuni) were recovered from the RE-cmeABC screening. We detected 122 (11.2%) RE-cmeABC-positive isolates of chicken origin, including 111 (70.7%) C. jejuni and 11 (1.2%) C. coli. This multidrug efflux pump is more prevalent among C. jejuni than C. coli. The level of resistance was significantly different in 111 RE-cmeABC-positive C. jejuni versus 46 RE-cmeABC-negative C. jejuni for florfenicol, clindamycin, and erythromycin (P < 0.05), but not for ciprofloxacin (CIP), TET, and gentamicin (GEN). However, the isolates harboring RE-cmeABC could shift the minimum inhibitory concentration distribution to the higher range for CIP and TET. Pulsed-field gel electrophoresis (PFGE) analysis suggested that horizontal transmission might be involved in the dissemination of RE-cmeABC in Shanghai and Guangdong, while clonal expansion was predominant in Shandong. Three isolates shared the indiscriminate PFGE types of RE-cmeABC-positive C. jejuni isolates in Shanghai and Guangdong, and four isolates in Shanghai and Shandong. Our study suggests the possibility of a wide dissemination of RE-cmeABC in Campylobacter of food-animal origin, which would pose a significant threat to public health.展开更多
RE-CmeABC is a variant of the efflux pump CmeABC in the major zoonotic pathogen Campylobacter,which is much more potent in conferring resistance to various antibiotics for the treatment of Campylobacter infections in ...RE-CmeABC is a variant of the efflux pump CmeABC in the major zoonotic pathogen Campylobacter,which is much more potent in conferring resistance to various antibiotics for the treatment of Campylobacter infections in both veterinary and medical clinics.This potent multidrug efflux pump RE-CmeABC is widely distributed and disseminated around the world,posing a serious threat to public health.In this study,we targeted the key efflux protein RE-CmeB of RE-CmeABC to explore promising efflux pump inhibitors derived from natural products to improve the multidrug resistance of Campylobacter.We constructed a protein screening model and utilized virtual screening techniques,such as molecular docking,to identify potential efflux pump inhibitors from natural product databases.The activity and safety of these candidates were subsequently evaluated,and ZINC338037 was shown to inhibit antibiotic extrusion and restore the susceptibility of multidrug-resistant Campylobacter.In summary,a potential multidrug efflux pump inhibitor was identified and is expected to be developed as an adjuvant drug for the treatment of clinical infections caused by multidrug-resistant Campylobacter.展开更多
文摘Campylobacter spp. are the leading cause of human gastroenteritis worldwide. RE-CmeABC is a newly identified resistance-enhancing multidrug efflux pump of Campylobacter spp. (C. spp.) that confers high-level resistance to fluoroquinolones, phenicols, macrolides, and tetracyclines (TETs), all of which are critical drugs in both human and veterinary medicine. In this study, we analyzed the presence and antimicrobial susceptibility of RE-cmeABC-positive Campylobacter isolates of food-animal origin from three representative regions (Shandong, Shanghai, and Guangdong) in China over three successive years, from 2014 to 2016. A total of 1088 Campylobacter isolates (931 C. coli and 157 C. jejuni) were recovered from the RE-cmeABC screening. We detected 122 (11.2%) RE-cmeABC-positive isolates of chicken origin, including 111 (70.7%) C. jejuni and 11 (1.2%) C. coli. This multidrug efflux pump is more prevalent among C. jejuni than C. coli. The level of resistance was significantly different in 111 RE-cmeABC-positive C. jejuni versus 46 RE-cmeABC-negative C. jejuni for florfenicol, clindamycin, and erythromycin (P < 0.05), but not for ciprofloxacin (CIP), TET, and gentamicin (GEN). However, the isolates harboring RE-cmeABC could shift the minimum inhibitory concentration distribution to the higher range for CIP and TET. Pulsed-field gel electrophoresis (PFGE) analysis suggested that horizontal transmission might be involved in the dissemination of RE-cmeABC in Shanghai and Guangdong, while clonal expansion was predominant in Shandong. Three isolates shared the indiscriminate PFGE types of RE-cmeABC-positive C. jejuni isolates in Shanghai and Guangdong, and four isolates in Shanghai and Shandong. Our study suggests the possibility of a wide dissemination of RE-cmeABC in Campylobacter of food-animal origin, which would pose a significant threat to public health.
基金supported by grants from the National Key Research and Development Program of China(no.2023YFD1801000)the National Natural Science Foundation of China(no.32473090)+2 种基金the Natural Science Foundation of Henan Province(no.232300421037)the Henan Province University Young Backbone Teachers Training Program(no.2023GGJS031)Graduate Education Reform Project of Henan Agricultural University(no.NDYJS2023-26).
文摘RE-CmeABC is a variant of the efflux pump CmeABC in the major zoonotic pathogen Campylobacter,which is much more potent in conferring resistance to various antibiotics for the treatment of Campylobacter infections in both veterinary and medical clinics.This potent multidrug efflux pump RE-CmeABC is widely distributed and disseminated around the world,posing a serious threat to public health.In this study,we targeted the key efflux protein RE-CmeB of RE-CmeABC to explore promising efflux pump inhibitors derived from natural products to improve the multidrug resistance of Campylobacter.We constructed a protein screening model and utilized virtual screening techniques,such as molecular docking,to identify potential efflux pump inhibitors from natural product databases.The activity and safety of these candidates were subsequently evaluated,and ZINC338037 was shown to inhibit antibiotic extrusion and restore the susceptibility of multidrug-resistant Campylobacter.In summary,a potential multidrug efflux pump inhibitor was identified and is expected to be developed as an adjuvant drug for the treatment of clinical infections caused by multidrug-resistant Campylobacter.
