Correlation between phenotypic virulence traits and antibiotic resistance in Pseudomonas aeruginosa clinical isolates

Nassar, O.M.; Desouky, Said E.; El-sherbeiny, Gamal M.; Abu-Elghait, Mohammed

doi:10.1016/j.micpath.2021.105339

Cited by 25 publications

(17 citation statements)

References 46 publications

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“…Finally, we tested the compound against PA clinical strains isolated from the respiratory tract of patients since it is well known that PAO1, a strain domesticated by extensive use in the laboratory, might produce results far from in vivo conditions for different virulence-related phenotypes ( El-Shaer et al, 2016 ). In accordance with the genetic diversity and phenotypic heterogeneity of P. aeruginosa field strains ( Finnan et al, 2004 ; Lebreton et al, 2021 ; Nassar et al, 2022 ), our clinical isolates significantly differed as regard pyocyanin production and swarming motility (data not shown). Although the clinical strains responded differently to treatment, overall, we reported a significant reduction in the production of pyocyanin, swarming and elastase B in most strains tested ( Figure 6 ).…”

Section: Discussionsupporting

confidence: 79%

A novel phenolic derivative inhibits AHL-dependent quorum sensing signaling in Pseudomonas aeruginosa

et al. 2022

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Increasing antibiotic resistance and the decline in the pharmaceutical industry’s investments have amplified the need for novel treatments for multidrug-resistant bacteria. Quorum sensing (QS) inhibitors reduce pathogens’ virulence without selective pressure on bacteria and provide an alternative to conventional antibiotic-based therapies. P. aeruginosa uses complex QS signaling to control virulence and biofilm formation. We aimed to identify inhibitors of P. aeruginosa QS acting on acyl-homoserine lactones (AHL)-mediated circuits. Bioluminescence and qRT-PCR assays were employed to screen a library of 81 small phenolic derivatives to reduce AHL-dependent signaling. We identified GM-50 as the most active compound inhibiting the expression of AHL-regulated genes but devoid of cytotoxic activity in human epithelial cells and biocidal effects on bacteria. GM-50 reduces virulence factors such as rhamnolipids, pyocyanin, elastase secretion, and swarming motility in P. aeruginosa PAO1 laboratory strain. By molecular docking, we provide evidence that GM-50 highly interacts with RhlR. GM-50 significantly improved aztreonam-mediated biofilm disruption. Moreover, GM-50 prevents adhesion of PAO1 and inflammatory damage in the human A549 cell line and protects Galleria mellonella from PAO1-mediated killing. GM-50 significantly reduces virulence factors in 20 P. aeruginosa clinical isolates from patients with respiratory tract infections. In conclusion, GM-50 inhibits AHL-signaling, reduces virulence factors, enhances the anti-biofilm activity of aztreonam, and protects G. mellonella larvae from damage induced by P. aeruginosa. Since GM-50 is active on clinical strains, it represents a starting point for identifying and developing new phenolic derivatives acting as QS-inhibitors in P. aeruginosa infections.

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Section: Discussionsupporting

confidence: 79%

A novel phenolic derivative inhibits AHL-dependent quorum sensing signaling in Pseudomonas aeruginosa

et al. 2022

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“…This is of particular interest since there are conflicting observations in the literature regarding a correlation between P. aeruginosa resistance to antibiotics and selected virulence traits. Indeed, on one hand, recent contradictory studies suggest that variations in the expression of virulence factors, particularly biofilm formation, are not correlated with antibiotic resistance in MDR P. aeruginosa strains [81] or, on the opposite, are statistically correlated with virulence traits in a panel of clinical isolates [82]. All these data reinforce the interest in studying potential correlations between xenobiotics and virulence traits, especially from a mechanistic point of view, in order to develop new control strategies to counter infections.…”

Section: Discussionmentioning

confidence: 99%

Effect of Phthalates and Their Substitutes on the Physiology of Pseudomonas aeruginosa

et al. 2022

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Phthalates are used in a variety of applications—for example, as plasticizers in polyvinylchloride products to improve their flexibility—and can be easily released into the environment. In addition to being major persistent organic environmental pollutants, some phthalates are responsible for the carcinogenicity, teratogenicity, and endocrine disruption that are notably affecting steroidogenesis in mammals. Numerous studies have thus focused on deciphering their effects on mammals and eukaryotic cells. While multicellular organisms such as humans are known to display various microbiota, including all of the microorganisms that may be commensal, symbiotic, or pathogenic, few studies have aimed at investigating the relationships between phthalates and bacteria, notably regarding their effects on opportunistic pathogens and the severity of the associated pathologies. Herein, the effects of phthalates and their substitutes were investigated on the human pathogen, Pseudomonas aeruginosa, in terms of physiology, virulence, susceptibility to antibiotics, and ability to form biofilms. We show in particular that most of these compounds increased biofilm formation, while some of them enhanced the bacterial membrane fluidity and altered the bacterial morphology.

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“…They are responsible for chronic infection and can decrease the sensitivity of P. aeruginosa to drugs as much as 1,000-fold ( Anwar et al, 1990 ). In multidrug resistance P. aeruginosa isolates, the biofilm-forming ability was significantly higher ( Nassar et al, 2022 ). Motility is another important virulence feature associated with initial acute infection and chronic infection of P. aeruginosa .…”

Section: Discussionmentioning

confidence: 99%

Sennoside A inhibits quorum sensing system to attenuate its regulated virulence and pathogenicity via targeting LasR in Pseudomonas aeruginosa

Han

Nan²,

Cai³

et al. 2022

Front. Microbiol.

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Pseudomonas aeruginosa is an important opportunistic pathogen, and the emergence of drug resistance greatly increased the difficulty of treating its infection. Cell density-dependent quorum sensing (QS) system not only regulates the virulence but also associates with the drug resistance of P. aeruginosa. Screening for agents targeting QS to inhibit bacterial virulence and pathogenicity is considered a promising strategy to combat P. aeruginosa infection. In the present study, sennoside A was found to be able to inhibit the QS expression of P. aeruginosa at subinhibitory concentrations. The QS-regulated virulence factors, including protease, elastase, rhamnolipid, and pyocyanin, were also inhibited by sennoside A at both transcriptional and translational levels. Moreover, sennoside A could suppress the motility of twitching, swimming, and swarming as well as the biofilm formation, which is associated with the acute and chronic infections of P. aeruginosa in a dose-dependent manner. The attenuated pathogenicity of P. aeruginosa by sennoside A was further verified by Chinese cabbage, Drosophila melanogaster, and Caenorhabditis elegans infection analysis. Further study found that sennoside A might target the las system, mainly LasR, to interfere with QS. All the results indicate that sennoside A could inhibit the QS system to attenuate its regulated virulence and pathogenicity via mainly targeting LasR in P. aeruginosa and further research to identify its anti-QS activity for other Gram-negative bacteria is warranted.

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Correlation between phenotypic virulence traits and antibiotic resistance in Pseudomonas aeruginosa clinical isolates

Cited by 25 publications

References 46 publications

A novel phenolic derivative inhibits AHL-dependent quorum sensing signaling in Pseudomonas aeruginosa

A novel phenolic derivative inhibits AHL-dependent quorum sensing signaling in Pseudomonas aeruginosa

Effect of Phthalates and Their Substitutes on the Physiology of Pseudomonas aeruginosa

Sennoside A inhibits quorum sensing system to attenuate its regulated virulence and pathogenicity via targeting LasR in Pseudomonas aeruginosa

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