Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health...Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health Organization (WHO). The efflux pumps are the main cause for the increasing antibiotic resistance of A. baumannii originated from nosocomial infection. The progressive resistance of A. baumannii even on the recent drugs (tigecycline and fosfomycin) reduces to very effective antibiotic scale. With attention focused on MDR and pan-drug-resistant (PDR) in A. baumannii multiple works on efflux pumps chemical inhibitor (NMP, PAβN, omeprazole, verapamil, reserpine, CCCP) are still in progress. Certain inhibitors from plants (Biricodar and timcodar, Falvone, Mahonia, Dalea versicolor, Lycopus europaeus, and Rosmarinus officinalis) have the capability to have such compounds according to their very significant synergistic effect with antibiotics. In this review we focused on the growth of antibiotic resistance to explain the mechanism of efflux pumps into these different super families and a comprehensive understanding of the extrusion, regulation and physiology role of drug efflux pumps in the essential development of anti-resistivity drugs. We recapitulated the evolution of the work carried out in these fields during the last years and in the course of elaboration, with the aim of increasing the chances of decreasing bacterial resistivity to antibiotics.展开更多
Tigecycline serves as a critical“final-resort”antibiotic for treating bacterial infections caused by multidrug-resistant bacteria for which treatment options are severely limited.The increasing prevalence of tigecyc...Tigecycline serves as a critical“final-resort”antibiotic for treating bacterial infections caused by multidrug-resistant bacteria for which treatment options are severely limited.The increasing prevalence of tigecycline resistance,particularly among Gram-negative bacteria,is a major concern.Various mechanisms have been iden-tified as contributors to tigecycline resistance,including upregulation of nonspecific Resistance Nodulation Divi-sion(RND)efflux pumps due to mutations in transcriptional regulators,enzymatic modification of tigecycline by monooxygenase enzymes,and mutations affecting tigecycline binding sites.This review aims to consolidate our understanding of tigecycline resistance mechanisms in Gram-negative bacteria and offer insights and perspectives for further drug development.展开更多
文摘Acinetobacter baumannii has greatly increased its degree of resistance to become multidrug resistant (MDR) over the past 30 years and is on the red line of the most widely replicated bacteria according to World Health Organization (WHO). The efflux pumps are the main cause for the increasing antibiotic resistance of A. baumannii originated from nosocomial infection. The progressive resistance of A. baumannii even on the recent drugs (tigecycline and fosfomycin) reduces to very effective antibiotic scale. With attention focused on MDR and pan-drug-resistant (PDR) in A. baumannii multiple works on efflux pumps chemical inhibitor (NMP, PAβN, omeprazole, verapamil, reserpine, CCCP) are still in progress. Certain inhibitors from plants (Biricodar and timcodar, Falvone, Mahonia, Dalea versicolor, Lycopus europaeus, and Rosmarinus officinalis) have the capability to have such compounds according to their very significant synergistic effect with antibiotics. In this review we focused on the growth of antibiotic resistance to explain the mechanism of efflux pumps into these different super families and a comprehensive understanding of the extrusion, regulation and physiology role of drug efflux pumps in the essential development of anti-resistivity drugs. We recapitulated the evolution of the work carried out in these fields during the last years and in the course of elaboration, with the aim of increasing the chances of decreasing bacterial resistivity to antibiotics.
基金supported by the National Key Research and De-velopment Program of China[grant number 2022YFE0199800]Key R&D Program of Shandong Province[grant number 2020CXGC011305]+1 种基金Shandong Provincial Natural Science Foundation[grant number ZR2020MH308]the National Natural Science Foundation of China[grant number 82,271,658].
文摘Tigecycline serves as a critical“final-resort”antibiotic for treating bacterial infections caused by multidrug-resistant bacteria for which treatment options are severely limited.The increasing prevalence of tigecycline resistance,particularly among Gram-negative bacteria,is a major concern.Various mechanisms have been iden-tified as contributors to tigecycline resistance,including upregulation of nonspecific Resistance Nodulation Divi-sion(RND)efflux pumps due to mutations in transcriptional regulators,enzymatic modification of tigecycline by monooxygenase enzymes,and mutations affecting tigecycline binding sites.This review aims to consolidate our understanding of tigecycline resistance mechanisms in Gram-negative bacteria and offer insights and perspectives for further drug development.