Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors

Gaurav, Abhishek; P, Bakht; Saini, Mahak; Pandey, Shivam; Pathania, Ranjana

doi:10.1099/mic.0.001333

Cited by 60 publications

(30 citation statements)

References 114 publications

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“…Another possible mechanism of antibiotic resistance in biofilms is the increased expression of bacterial efflux pumps [84,85]. Efflux pumps, which are membrane proteins necessary to maintain bacterial homeostasis by expelling toxic substances, are present in all types of bacteria [86].…”

Section: Increased Expression Of Efflux Pumps In Biofilmsmentioning

confidence: 99%

Bacterial Biofilm Formation on Biomaterials and Approaches to Its Treatment and Prevention

Yin

Cheng

et al. 2023

IJMS

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Bacterial biofilms can cause widespread infection. In addition to causing urinary tract infections and pulmonary infections in patients with cystic fibrosis, biofilms can help microorganisms adhere to the surfaces of various medical devices, causing biofilm-associated infections on the surfaces of biomaterials such as venous ducts, joint prostheses, mechanical heart valves, and catheters. Biofilms provide a protective barrier for bacteria and provide resistance to antimicrobial agents, which increases the morbidity and mortality of patients. This review summarizes biofilm formation processes and resistance mechanisms, as well as the main features of clinically persistent infections caused by biofilms. Considering the various infections caused by clinical medical devices, we introduce two main methods to prevent and treat biomaterial-related biofilm infection: antibacterial coatings and the surface modification of biomaterials. Antibacterial coatings depend on the covalent immobilization of antimicrobial agents on the coating surface and drug release to prevent and combat infection, while the surface modification of biomaterials affects the adhesion behavior of cells on the surfaces of implants and the subsequent biofilm formation process by altering the physical and chemical properties of the implant material surface. The advantages of each strategy in terms of their antibacterial effect, biocompatibility, limitations, and application prospects are analyzed, providing ideas and research directions for the development of novel biofilm infection strategies related to therapeutic materials.

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Section: Increased Expression Of Efflux Pumps In Biofilmsmentioning

confidence: 99%

Bacterial Biofilm Formation on Biomaterials and Approaches to Its Treatment and Prevention

Yin

Cheng

et al. 2023

IJMS

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“…Moreover, the efflux pump that is responsible for the removal of harmful compounds from the inside of the cells may differ in G-ve bacteria compared to G+ve. The green formed Ag-NPs can overcome the efflux pump mechanism in G-ve bacteria, leading to accumulation inside the cells and hence enhance their antibacterial activity [ 53 ].…”

Section: Resultsmentioning

confidence: 99%

Exploring the Antimicrobial, Antioxidant, and Antiviral Potential of Eco-Friendly Synthesized Silver Nanoparticles Using Leaf Aqueous Extract of Portulaca oleracea L.

Abdel-Rahman,

Alshallash,

Eid

et al. 2024

Pharmaceuticals

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Herein, the prospective applications of green fabricated silver nanoparticles (Ag-NPs) within the biomedical field were investigated. The leaf aqueous extract of Portulaca oleracea L., a safe, cheap, and green method, was used to fabricate Ag-NPs. The maximum plasmon resonance of synthesized NPs has appeared at 420 nm. The various biomolecules present in the plant extract to assemble spherical Ag-NPs with sizes of 5–40 nm were analyzed using Fourier transform infrared and transmission electron microscopy. The Ag was the major content of the formed Ag-NPs with an atomic percent of 54.95% and weight percent of 65.86%, as indicated by EDX. The crystallographic structure of synthesized NPs was confirmed by the diffraction of the X-ray. The dynamic light scattering exhibits the homogeneity and mono-dispersity nature with a polydispersity index of 0.37 in the colloidal fluid and a zeta potential value of –36 mV. The synthesized Ag-NPs exhibited promising antimicrobial efficacy toward various prokaryotic and eukaryotic pathogenic microorganisms with low MIC values of 12.5 µg mL−1 and 6.25 µg mL−1, respectively. Additionally, the P. oleracea-formed Ag-NPs showed optimistic antioxidant activity assessed by DPPH and H2O2 assay methods with the highest scavenging percentages of 88.5 ± 2.3% and 76.5 ± 1.7%, respectively, at a concentration of 200 µg mL−1. Finally, the biosynthesized Ag-NPs showed high antiviral properties toward the hepatitis A virus and Cox-B4 with inhibition percentages of 79.16 ± 0.5% and 73.59 ± 0.8%, respectively. Overall, additional research is essential to explore the Ag-NP-based aqueous extract of P. oleracea for human health. In the current investigation the use of synthesized Ag-NPs as antimicrobial, antioxidant, and antiviral agents to protect against pathogenic microbes, degenerative diseases caused by various oxidative stresses, and deadly viruses is recommended.

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“…However, efflux pumps are one of the most important arsenals for a resistant bacterial pathogen . Efflux pumps play a critical role in the pathophysiology of many human pathogens. − What makes bacterial efflux pumps so special is broad substrate specificity, that is, a single type of efflux pump can expel multiple antibiotics. Active expression of a single efflux pump can cause treatment failure against multiple antibiotics. , Furthermore, efflux pumps also play an important role in biofilm formation by transporting various biofilm matrix components …”

Section: Discussionmentioning

confidence: 99%

Small Molecule IITR08367 Potentiates Antibacterial Efficacy of Fosfomycin against Acinetobacter baumannii by Efflux Pump Inhibition

Saini,

Gaurav,

Hussain

et al. 2024

ACS Infect. Dis.

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Fosfomycin is a broad-spectrum single-dose therapy approved for treating lower urinary tract infections. Acinetobacter baumannii, one of the five major UTI-causing pathogens, is intrinsically resistant to fosfomycin. Reduced uptake and active efflux are major reasons for this intrinsic resistance. AbaF, a major facilitator superfamily class of transporter in A. baumannii, is responsible for fosfomycin efflux and biofilm formation. This study describes the identification and validation of a novel smallmolecule efflux pump inhibitor that potentiates fosfomycin efficacy against A. baumannii. An AbaF inhibitor screening was performed against Escherichia coli KAM32/pUC18_abaF, using the noninhibitory concentration of 24 putative efflux pump inhibitors. The inhibitory activity of IITR08367 [bis(4-methylbenzyl) disufide] against fosfomycin/H + antiport was validated using ethidium bromide efflux, quinacrine-based proton-sensitive fluorescence, and membrane depolarization assays. IITR08367 inhibits fosfomycin/H + antiport activity by perturbing the transmembrane proton gradient. IITR08367 is a nontoxic molecule that potentiates fosfomycin activity against clinical strains of A. baumannii and prevents biofilm formation by inhibiting efflux pump (AbaF). The IITR08367-fosfomycin combination reduced bacterial burden by > 3 log 10 in kidney and bladder tissue in the murine UTI model. Overall, fosfomycin, in combination with IITR08367, holds the potential to treat urinary tract infections caused by A. baumannii.

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Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors

Cited by 60 publications

References 114 publications

Bacterial Biofilm Formation on Biomaterials and Approaches to Its Treatment and Prevention

Bacterial Biofilm Formation on Biomaterials and Approaches to Its Treatment and Prevention

Exploring the Antimicrobial, Antioxidant, and Antiviral Potential of Eco-Friendly Synthesized Silver Nanoparticles Using Leaf Aqueous Extract of Portulaca oleracea L.

Small Molecule IITR08367 Potentiates Antibacterial Efficacy of Fosfomycin against Acinetobacter baumannii by Efflux Pump Inhibition

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