Repositioning secnidazole as a novel virulence factors attenuating agent in Pseudomonas aeruginosa

Saleh, Moustafa M.; Abbas, Hisham A.; Askoura, Momen

doi:10.1016/j.micpath.2018.11.042

Cited by 19 publications

(17 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to evaluate the effect of metronidazole on P. mirabilis virulence, we used metronidazole in sub-MICs to avoid any effect on bacterial growth. In a previous work, metronidazole and secnidazole which harbor similar chemical moiety were efficiently able to curtail the Pseudomonas aeruginosa pathogenesis [41,42]. Obviously, metronidazole has no influence at all on the bacterial growth.…”

Section: Discussionmentioning

confidence: 90%

Not Only Antimicrobial: Metronidazole Mitigates the Virulence of Proteus mirabilis Isolated from Macerated Diabetic Foot Ulcer

et al. 2021

Self Cite

View full text Add to dashboard Cite

Diabetic foot ulcers are recognized to be a severe complication of diabetes, increasing the risk of amputation and death. The bacterial infection of Diabetic foot ulcers with virulent and resistant bacteria as Proteus mirabilis greatly worsens the wound and may not be treated with conventional therapeutics. Developing new approaches to target bacterial virulence can be helpful to conquer such infections. In the current work, we evaluated the anti-virulence activities of the widely used antibacterial metronidazole. The minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentrations (MEBC) were determined for selected antibiotics which P. mirabilis was resistant to them in the presence and absence of metronidazole in sub-MIC. The effect of metronidazole in sub-MIC on P. mirabilis virulence factors as production of exoenzymes, motilities, adhesion and biofilm formation, were evaluated. Furthermore, molecular docking of metronidazole into P. mirabilis adhesion and essential quorum sensing (QS) proteins, was performed. The results revealed a significant ability of metronidazole to in-vitro inhibit P. mirabilis virulence factors and antagonize its essential proteins. Moreover, metronidazole markedly decreased the MICs and MBECs of tested antibiotics. Conclusively, metronidazole in sub-MIC is a plausible anti-virulence and anti-QS agent that can be combined to other antibiotics as anti-virulence adjuvant to defeat aggressive infections.

show abstract

Section: Discussionmentioning

confidence: 90%

Not Only Antimicrobial: Metronidazole Mitigates the Virulence of Proteus mirabilis Isolated from Macerated Diabetic Foot Ulcer

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The antibiotic clofoctol ( 72 ) presented the most active inhibition of virulence in P. aeruginosa by targeting the transcriptional regulator PqsR, which specifically inhibits the expression of pqs ‐controlled QS virulence traits, such as pyocyanin production, swarming motility, and biofilm formation . Secnidazole ( 73 ), a known nitroimidazole drug, has been used for the treatment of many infections caused by anaerobic pathogens and has shown a powerful inhibitory effect on P. aeruginosa virulence factors in recent studies . The antidiabetic agent metformin ( 74 ) and the Chinese herb phillyrin ( 75 ) were also identified to significantly reduce the production of the pigments violacein and pyocyanin in recent studies …”

Section: Pigments Of Representative Colored Pathogens and Their Inhibmentioning

confidence: 99%

“…154 Secnidazole (73), a known nitroimidazole drug, has been used for the treatment of many infections caused by anaerobic pathogens and has shown a powerful inhibitory effect on P. aeruginosa virulence factors in recent studies. 155 The antidiabetic agent metformin (74) and the Chinese herb phillyrin (75) were also identified to significantly reduce the production of the pigments violacein and pyocyanin in recent studies. 156,157 3.8 | Other strategies to discover pyocyanin inhibitors Signaling molecule analogs exhibit excellent anti-pyocyanin activity and attenuate QS virulence.…”

Section: Pyocyanin Inhibitors From a Natural Product Library And Drmentioning

confidence: 99%

Targeting virulence factors as an antimicrobial approach: Pigment inhibitors

et al. 2019

Medicinal Research Reviews

View full text Add to dashboard Cite

The fascinating and dangerous colored pathogens contain unique chemically pigmented molecules, which give varied and efficient assistance as virulence factors to the crucial reproduction and growth of microbes. Therefore, multiple novel strategies and inhibitors have been developed in recent years that target virulence factor pigments. However, despite the importance and significance of this topic, it has not yet been comprehensively reviewed. Moreover, research groups around the world have made successful progress against antibacterial infections by targeting pigment production, including our serial works on the discovery of CrtN inhibitors against staphyloxanthin production in Staphylococcus aureus. On the basis of the previous achievements and recent progress of our group in this field, this article will be the first comprehensive review of pigment inhibitors against colored pathogens, especially S. aureus infections, and this article includes design strategies, representative case studies, advantages, limitations, and perspectives to guide future research.

show abstract

“…Proteolytic enzymes secreted by microorganisms play a significant role in the course of sepsis and eye infection due to the degradation of immunoglobulins and fibrin [6]. The presence of numerous virulence factors and formation of biofilm by P. aeruginosa is regulated through the mechanism of "bacteria to bacteria" communication-Quorum Sensing (QS) [2,[6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Antibiotic Resistance, Biofilm Formation, and Presence of Genes Encoding Virulence Factors in Strains Isolated from the Pharmaceutical Production Environment

et al. 2021

View full text Add to dashboard Cite

The spread of bacterial resistance to antibiotics affects various areas of life. The aim of this study was to assess the occurrence of Pseudomonas aeruginosa, and other bacteria mainly from orders Enterobacterales and Staphylococcus in the pharmaceutical production sites, and to characterize isolated strains in the aspects of antibiotic resistance, biofilm formation, and presence of genes encoding virulence factors. Genes encoding selected virulence factors were detected using PCR techniques. Antimicrobial susceptibility testing was applied in accordance with the EUCAST recommendations. A total of 46 P. aeruginosa strains were isolated and 85% strains showed a strong biofilm-forming ability. The qualitative identification of genes taking part in Quorum Sensing system demonstrated that over 89% of strains contained lasR and rhlI genes. An antimicrobial susceptibility testing revealed nine strains resistant to at least one antibiotic, and two isolates were the metallo-β-lactamase producers. Moreover, the majority of P. aeruginosa strains contained genes encoding various virulence factors. Presence of even low level of pathogenic microorganisms or higher level of opportunistic pathogens and their toxic metabolites might result in the production inefficiency. Therefore, the prevention of microbial contamination, effectiveness of sanitary and hygienic applied protocols, and constant microbiological monitoring of the environment are of great importance.

show abstract

Repositioning secnidazole as a novel virulence factors attenuating agent in Pseudomonas aeruginosa

Cited by 19 publications

References 34 publications

Not Only Antimicrobial: Metronidazole Mitigates the Virulence of Proteus mirabilis Isolated from Macerated Diabetic Foot Ulcer

Not Only Antimicrobial: Metronidazole Mitigates the Virulence of Proteus mirabilis Isolated from Macerated Diabetic Foot Ulcer

Targeting virulence factors as an antimicrobial approach: Pigment inhibitors

Antibiotic Resistance, Biofilm Formation, and Presence of Genes Encoding Virulence Factors in Strains Isolated from the Pharmaceutical Production Environment

Contact Info

Product

Resources

About