Expression of MexAB-OprM efflux pump and OprD porin in carbapenemase producing Pseudomonas aeruginosa clinical isolates

Beig, Masoumeh; Taheri, Mohammad; Arabestani, Mohammad Reza

doi:10.1016/j.genrep.2020.100744

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…MexAB-OprM can export several antibiotics, including quinolones, macrolides, tetracyclines, lincomycin, chloramphenicol, novobiocin, and most β-lactams [ 79 ], and it has been shown to be a major factor in the resistance to the herbal antimicrobial compound carvacrol [ 81 ]. Overexpression of this efflux pump is associated with resistance to most antipseudomonal antibiotics, except for colistin [ 80 ], and carbapenemase-producing carbapenem-resistant P. aeruginosa strains often show an increased mexAB-oprM expression, which could be contributing to its resistance to carbapenems [ 145 ]. Moreover, it has been shown that overexpression of MexAB-OprM and AmpC, a chromosomally encoded class C β-lactamase that contributes to the resistance to many penicillins [ 146 , 147 ], has synergistic effects on the resistance of P. aeruginosa to most antipseudomonal β-lactams, except for ceftolozane/tazobactam, imipenem, and imipenem/relebactam [ 148 ].…”

Section: Efflux Pumps As a Mechanism Of Antimicrobial Resistance In ...mentioning

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: Efflux Pumps As a Mechanism Of Antimicrobial Resistance In ...mentioning

confidence: 99%

Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

Lorusso

Carrara

Barroso

et al. 2022

IJMS

106

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“…This efflux pump’s significance extends beyond antibiotic resistance, as it also plays a key role in counteracting antimicrobial compounds derived from plants, exemplified by its ability to expel carvacrol and numerous other plant-based agents [ 98 ]. Carbapenemase-producing carbapenem-resistant P. aeruginosa strains often exhibit heightened expression of MexAB-OprM, contributing significantly to their resistance against carbapenems [ 164 ]. Furthermore, the simultaneous overexpression of MexAB-OprM and AmpC β-lactamase synergistically enhances P. aeruginosa ’s resistance to a wide range of antipseudomonal β-lactams, exemplifying the intricate interplay between these mechanisms [ 165 ].…”

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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“…Briefly, 3-5 colonies of overnight bacterial culture were suspended again in 500 µl of sterile distilled water, boiled for 30 mins, and then centrifuged at 14000g for 5 mins to pellet cell debris. en, the extracted DNA was stored at −20°C [16,17]. e quantity and quality of the DNA were determined using a nano spectrophotometer (NanoDrop ND-1000, Biocompare, San Francisco, USA) and gel electrophoresis.…”

Section: Carbanp Test (Cnpt)mentioning

confidence: 99%

Comparison of Different Phenotypic Tests versus PCR in the Detection of Carbapenemase-Producing Pseudomonas aeruginosa Isolates in Hamadan, Iran

Beig

Taheri

Arabestani

2021

International Journal of Microbiology

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In recent years, the prevalence of carbapenem-resistant Pseudomonas aeruginosa isolates has become a worldwide concern. Rapid and accurate detection of carbapenemase-producing P. aeruginosa isolates is so important. The aim of this study was to evaluate the performance of the phenotypic methods such as Modified Hodge test (MHT), CarbaNP (CNPt), combined double-disk synergy test (CDDT), and carbapenem inactivation method (CIM) for rapid and accurate detection of clinical carbapenemase production of P. aeruginosa isolates. This study was performed on 97 P. aeruginosa strains, which were isolated from clinical samples in Hamadan hospitals, western Iran in 2017-2018. Antibiotic susceptibility testing was performed using disk diffusion and minimum inhibitory concentration (MIC) by E-test method. We evaluated the performance of MHT, CarbaNP, CDDT, and CIM tests in comparison to polymerase chain reaction (PCR) for the detection of carbapenemase-producing isolates. Additionally, the presence of carbapenem-resistant genes was investigated using the PCR method. Our findings showed that the highest resistance was to cefoxitin (94.8%). Moreover, among the carbapenem antibiotics, the highest resistance was to imipenem (49.4%). Among the 49 carbapenem-resistant isolates, 42 (85.7%) isolates were MIC positive. The results of phenotypic tests showed that CarbaNP, CIM, CDDT, and MHT tests were positive in (48/49, 97.95%), (46/49, 93.87%), (27/49, 57.44%), and (25/49, 53.19%) of isolates, respectively. CarbaNP and CIM tests showed high sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) compared to PCR in P. aeruginosa isolates. CarbaNP and CIM tests are highly sensitive and specific tests for identifying carbapenemase-producing P. aeruginosa isolates.

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Expression of MexAB-OprM efflux pump and OprD porin in carbapenemase producing Pseudomonas aeruginosa clinical isolates

Cited by 9 publications

References 24 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

Comparison of Different Phenotypic Tests versus PCR in the Detection of Carbapenemase-Producing Pseudomonas aeruginosa Isolates in Hamadan, Iran

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