Inhibition of biofilm and virulence properties of Pseudomonas aeruginosa by sub-inhibitory concentrations of aminoglycosides

Khan, Fazlurrahman; Lee, Jang-Won; Javaid, Aqib; Park, Seulki; Kim, Young‐Mog

doi:10.1016/j.micpath.2020.104249

Cited by 25 publications

(20 citation statements)

References 86 publications

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“…This might account for the role of macrolides in the attenuation of P. aeruginosa inflammation at sub-inhibitory concentrations through the inhibition of virulence factors among other mechanisms [68,69]. Khan et al also showed that free aminoglycosides including gentamicin significantly inhibited virulence factors such as pyoverdine, protease and pyocyanin in P. aeruginosa strains [7,70]. Earlier studies demonstrated an increased inhibitory activity of liposomal antibiotics on protease, elastase, lipase and chitinase production [47,51,52].…”

Section: Discussionmentioning

confidence: 97%

“…For instance, Khan et al recently showed through an in silico docking analysis that aminoglycosides interact with P. aeruginosa QS receptor LasR. They proposed this to be a mechanism by which they inhibit QS associated virulence factors in the bacterium, as it prevents the binding of LasR receptor to 3OC 12 -HSL signals [7]. Furthermore, Burr et al reported that sub-inhibitory concentrations of erythromycin strongly inhibited the expression of P. aeruginosa QS genes such as LasR and PqsA in non-CF bronchiectasis airways [69].…”

Section: Discussionmentioning

confidence: 99%

“…Regulates elastase, protease, exotoxin A, biofilm formation and induces PQS and Rhl systems [34,35] Protease Immune invasion and host tissue damage [7,29] MexXY-OprM Aminoglycosides, fluoroquinolones, tetracyclines and macrolides [22][23][24] RhlI/R (C 4 -HSL)…”

Section: Mexab-oprmmentioning

confidence: 99%

“…They are the leading cause of death in CF [4]. Aminoglycosides and macrolides are commonly prescribed for the management of P. aeruginosa infections in CF, as they inhibit protein synthesis in the bacteria [2,[5][6][7][8]. Moreover, macrolides such as azithromycin are recommended for CF patients because they reduce pulmonary exacerbations over long periods [9,10].…”

Section: Introductionmentioning

confidence: 99%

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The Impact of an Efflux Pump Inhibitor on the Activity of Free and Liposomal Antibiotics against Pseudomonas aeruginosa

Gbian

Omri

2021

Pharmaceutics

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The eradication of Pseudomonas aeruginosa in cystic fibrosis patients has become continuously difficult due to its increased resistance to treatments. This study assessed the efficacy of free and liposomal gentamicin and erythromycin, combined with Phenylalanine arginine beta-naphthylamide (PABN), a broad-spectrum efflux pump inhibitor, against P. aeruginosa isolates. Liposomes were prepared and characterized for their sizes and encapsulation efficiencies. The antimicrobial activities of formulations were determined by the microbroth dilution method. Their activity on P. aeruginosa biofilms was assessed, and the effect of sub-inhibitory concentrations on bacterial virulence factors, quorum sensing (QS) signals and bacterial motility was also evaluated. The average diameters of liposomes were 562.67 ± 33.74 nm for gentamicin and 3086.35 ± 553.95 nm for erythromycin, with encapsulation efficiencies of 13.89 ± 1.54% and 51.58 ± 2.84%, respectively. Liposomes and PABN combinations potentiated antibiotics by reducing minimum inhibitory and bactericidal concentrations by 4–32 fold overall. The formulations significantly inhibited biofilm formation and differentially attenuated virulence factor production as well as motility. Unexpectedly, QS signal production was not affected by treatments. Taken together, the results indicate that PABN shows potential as an adjuvant of liposomal macrolides and aminoglycosides in the management of lung infections in cystic fibrosis patients.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Mexab-oprmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Impact of an Efflux Pump Inhibitor on the Activity of Free and Liposomal Antibiotics against Pseudomonas aeruginosa

Gbian

Omri

2021

Pharmaceutics

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“…Antibiotics have also shown great potential as QS inhibiting agents. For exsample, aminoglycosides, a commonly used class of antibiotics, exhibit biofilm inhibition by targeting the QS regulatory protein LasR in P. aeruginosa ( Khan et al, 2020a ; Khan et al, 2020b ).…”

Section: Strategies Of Exploiting New Qs Inhibiting Agentsmentioning

confidence: 99%

Regulatory Mechanisms and Promising Applications of Quorum Sensing-Inhibiting Agents in Control of Bacterial Biofilm Formation

et al. 2020

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A biofilm is an assemblage of microbial cells attached to a surface and encapsulated in an extracellular polymeric substance (EPS) matrix. The formation of a biofilm is one of the important mechanisms of bacterial resistance, which not only leads to hard-to-control bacterial infections in humans and animals but also enables bacteria to be a major problem in various fields, such as food processing, wastewater treatment and metalworking. Quorum sensing (QS) is a bacterial cell-to-cell communication process that depends on the bacterial population density and is mediated by small diffusible signaling molecules called autoinducers (AIs). Bacteria use QS to regulate diverse arrays of functions, including virulence and biofilm formation. Therefore, the interference with QS by using QS inhibiting agents, including QS inhibitors (QSIs) and quorum quenching (QQ) enzymes, to reduce or even completely repress the biofilm formation of pathogenic bacteria appears to be a promising approach to control bacterial infections. In this review, we summarize the mechanisms of QS-regulating biofilm formation and QS-inhibiting agents that control bacterial biofilm formation, strategies for the discovery of new QS inhibiting agents, and the current applications of QS-inhibiting agents in several fields to provide insight into the development of effective drugs to control pathogenic bacteria.

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Regulatory mechanisms of sub-inhibitory levels antibiotics agent in bacterial virulence

Liu

Zhang

Ding

et al. 2021

Appl Microbiol Biotechnol

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Inhibition of biofilm and virulence properties of Pseudomonas aeruginosa by sub-inhibitory concentrations of aminoglycosides

Cited by 25 publications

References 86 publications

The Impact of an Efflux Pump Inhibitor on the Activity of Free and Liposomal Antibiotics against Pseudomonas aeruginosa

The Impact of an Efflux Pump Inhibitor on the Activity of Free and Liposomal Antibiotics against Pseudomonas aeruginosa

Regulatory Mechanisms and Promising Applications of Quorum Sensing-Inhibiting Agents in Control of Bacterial Biofilm Formation

Regulatory mechanisms of sub-inhibitory levels antibiotics agent in bacterial virulence

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