Involvement of the SCO3366 efflux pump from S. coelicolor in rifampicin resistance and its regulation by a TetR regulator

Nag, Ankita; Mehra, Sarika

doi:10.1007/s00253-022-11837-x

Cited by 4 publications

(4 citation statements)

References 67 publications

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“…Efflux pumps evolved as a way for bacteria to interact with the environment [ 100 ]. Their ubiquitous presence in nature [ 101 ] allowed bacteria to survive in their ecological niches [ 38 ], protecting them from toxic compounds produced by other species of bacteria or by the host, antimicrobial molecules, reactive oxygen species (ROS), and toxic byproducts of biochemical degradation pathways [ 38 , 43 , 52 , 102 , 103 , 104 ]. Efflux pumps can be specific for only one substrate or can export a range of molecules [ 38 , 62 , 105 ].…”

Section: Function and Structure Of Efflux Pumpsmentioning

confidence: 99%

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

Lorusso

Carrara

Barroso

et al. 2022

IJMS

106

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Antimicrobial resistance is an old and silent pandemic. Resistant organisms emerge in parallel with new antibiotics, leading to a major global public health crisis over time. Antibiotic resistance may be due to different mechanisms and against different classes of drugs. These mechanisms are usually found in the same organism, giving rise to multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria. One resistance mechanism that is closely associated with the emergence of MDR and XDR bacteria is the efflux of drugs since the same pump can transport different classes of drugs. In Gram-negative bacteria, efflux pumps are present in two configurations: a transmembrane protein anchored in the inner membrane and a complex formed by three proteins. The tripartite complex has a transmembrane protein present in the inner membrane, a periplasmic protein, and a porin associated with the outer membrane. In Pseudomonas aeruginosa, one of the main pathogens associated with respiratory tract infections, four main sets of efflux pumps have been associated with antibiotic resistance: MexAB-OprM, MexXY, MexCD-OprJ, and MexEF-OprN. In this review, the function, structure, and regulation of these efflux pumps in P. aeruginosa and their actions as resistance mechanisms are discussed. Finally, a brief discussion on the potential of efflux pumps in P. aeruginosa as a target for new drugs is presented.

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Section: Function and Structure Of Efflux Pumpsmentioning

confidence: 99%

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

Lorusso

Carrara

Barroso

et al. 2022

IJMS

106

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“…Through these multifaceted contributions to bacterial survival strategies, efflux pumps play an indispensable role in bacterial evolution and ecology [ 131 ]. These pumps, widely distributed in nature, enabled bacteria to thrive in their ecological niches, protecting them from various harmful substances such as toxic compounds, antimicrobial molecules, reactive oxygen species (ROS), and degradation by-products [ 53 , 57 , 78 , 132 , 133 , 134 ]. RND efflux pumps exhibit a diverse range of substrate specificity, ranging from high selectivity for single compounds to the ability to transport a wide array of diverse compounds [ 54 , 78 , 135 ].…”

Section: Rnd Efflux Pumps In P Aeruginosa the Typ...mentioning

confidence: 99%

The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy

Avakh,

Grant,

Cheesman

et al. 2023

Antibiotics

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Pseudomonas aeruginosa (P. aeruginosa) poses a grave clinical challenge due to its multidrug resistance (MDR) phenotype, leading to severe and life-threatening infections. This bacterium exhibits both intrinsic resistance to various antipseudomonal agents and acquired resistance against nearly all available antibiotics, contributing to its MDR phenotype. Multiple mechanisms, including enzyme production, loss of outer membrane proteins, target mutations, and multidrug efflux systems, contribute to its antimicrobial resistance. The clinical importance of addressing MDR in P. aeruginosa is paramount, and one pivotal determinant is the resistance-nodulation-division (RND) family of drug/proton antiporters, notably the Mex efflux pumps. These pumps function as crucial defenders, reinforcing the emergence of extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains, which underscores the urgency of the situation. Overcoming this challenge necessitates the exploration and development of potent efflux pump inhibitors (EPIs) to restore the efficacy of existing antipseudomonal drugs. By effectively countering or bypassing efflux activities, EPIs hold tremendous potential for restoring the antibacterial activity against P. aeruginosa and other Gram-negative pathogens. This review focuses on concurrent MDR, highlighting the clinical significance of efflux pumps, particularly the Mex efflux pumps, in driving MDR. It explores promising EPIs and delves into the structural characteristics of the MexB subunit and its substrate binding sites.

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“…More importantly, the aggregation of surface-associated microorganisms forms biofilms, and the penetration specificity of antibiotics is directly related to the efficacy of OM ( 45 , 46 ). In addition to biofilm formation, both Gram-negative and Gram-positive bacteria can actively expel antibiotics from cells via efflux pumps, which is another major drug resistance mechanism ( 47 ). Gram-negative bacteria are usually more resistant to the action of anti-bacterial drugs than Gram-positive bacteria due to the presence of porins ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Comparing the efficacy of different antibiotic regimens on osteomyelitis: A network meta-analysis of animal studies

Shi

Wu²,

et al. 2022

Front. Med.

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BackgroundDespite the surge in the number of antibiotics used to treat preclinical osteomyelitis (OM), their efficacy remains inadequately assessed.ObjectiveTo establish network comparisons on the efficacy of antibiotic regimens on OM in animal studies.MethodsPubMed, Embase, Web of Science, and The Cochrane Library were searched from inception to March 2022 for relevant articles. Odds ratios (ORs) were generated for dichotomous variants, and the standard mean difference (SMD) was calculated for constant variables. The predominant outcomes were the effective rate of sterility, also known as sterility rates, as well as the bacterial counts at the end of the experiments and antibiotic concentrations in serum or bone. All the network meta-analyses were performed using STATA MP 16.0. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42022316544).ResultsA total of 28 eligible studies with 1,488 animals were included for data analysis, including 13 antibiotic regimens. Regarding the effective rate of sterility, glycopeptides (GLY), linezolid (LIN), rifampicin (RIF)+β-Lactam, and β-Lactam showed significant efficacy compared with placebo (OR ranging from 0.01 to 0.08). For radiological grade, only RIF+GLY (SMD: −5.92, 95%CI: −11.65 to −0.19) showed significant efficacy compared with placebo. As for reducing bacteria count, fosfomycin (FOS), tigecycline (TIG), GLY, LIN, RIF, RIF+β-Lactam, RIF+GLY, aminoglycosides (AMI), and clindamycin (CLI) showed significant efficacy compared with placebo (SMD ranging from −6.32 to −2.62). Moreover, the bone concentrations of GLY were higher 1 h after administration and the higher blood concentrations were higher after 1 h and 4 h compared with the other antibiotics.ConclusionMultiple antibiotic regimens showed significant efficacy in animals with OM, including increasing effective rates of sterility, reducing bacterial counts, and lowering radiological scores. Among them, RIF+GLY was the most promising treatment regimen owing to its optimal efficacy. Based on the preclinical studies included in our meta-analysis, head-to-head clinical randomized controlled trials are required to confirm these findings in humans.

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Involvement of the SCO3366 efflux pump from S. coelicolor in rifampicin resistance and its regulation by a TetR regulator

Cited by 4 publications

References 67 publications

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

The Art of War with Pseudomonas aeruginosa: Targeting Mex Efflux Pumps Directly to Strategically Enhance Antipseudomonal Drug Efficacy

Comparing the efficacy of different antibiotic regimens on osteomyelitis: A network meta-analysis of animal studies

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