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Piroxicam repurposing approach as an anti-virulence agent against methicillin resistant <i>Staphylococcus aureus</i> clinical isolates

Article

Last updated: 04 Jan 2025

Subjects

-

Tags

Pharmaceutical microbiology

Abstract

Background:  Methicillin resistant Staphylococcus aureus (MRSA) is a major pathogen that causes infections in a wide range due to its high virulence. Anti-virulence therapy is one of several strategies proposed to counteract antimicrobial resistance. FDA-approved drugs repurposing as antibacterial and anti-virulence agents is a promising and rapid approach. The study aimed to evaluate piroxicam effect, a repurposed drug, as anti-virulence agent against MRSA isolated from chronic infections. Methods: The minimum inhibitory concentration (MIC) of piroxicam against the MRSA isolates was estimated. The presence of various virulence factors including protease, hemolysin, staphyloxanthin and biofilm formation was assessed in the absence and presence of piroxicam at ½ MIC. The detection of agr genes was performed using PCR for agr typing of the isolates. Molecular docking studies was performed to investigate whether piroxicam can bind to specific virulence proteins. Results: Piroxicam exhibited an MIC of 2.5mg/ml against all tested isolates. Piroxicam ½ MIC caused a significant reduction in protease activity (20-100% inhibition), hemolysin activity (20.7-97.2% inhibition) and staphyloxanthin production (1.17 -94.63% inhibition). In terms of biofilm formation, there was a significant inhibition ranging from 4.6-76.1%. The isolates were either type agr1 (53.3%) or type agr3 (46.7%). The anti-virulence effect of piroxicam was confirmed through in-silico docking, which demonstrated interactions between piroxicam and virulence proteins. Conclusions: Piroxicam has significant anti-virulence and anti-biofilm effects at sub-MIC against MRSA isolates. Therefore, it can be concluded that piroxicam can be used as an anti-virulence agent against MRSA infections.

DOI

10.21608/mid.2024.271311.1805

Keywords

MRSA, Anti-virulence, piroxicam, biofilm formation, agr system

Authors

First Name

Ingy

Last Name

El-Soudany

MiddleName

Ibrahim

Affiliation

Microbiology and Immunology Department, Faculty of Pharmacy, Pharos University in Alexandria, Egypt

Email

ingy.elsoudany@pua.edu.eg

City

Alexandria

Orcid

0000-0001-9602-0185

First Name

Maged

Last Name

Elsawy

MiddleName

-

Affiliation

Pharmaceutical Chemistry department, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt

Email

maged.elsawy@pua.edu.eg

City

Alexandria

Orcid

-

First Name

Rasha

Last Name

Emad

MiddleName

-

Affiliation

Alexandria Main University Hospital Champollion street, Al Attarin, Alexandria, Egypt

Email

gs-rasha.emad@alexu.edu.eg

City

Alexandria

Orcid

0000-0002-8774-6635

First Name

Nancy

Last Name

Attia

MiddleName

Mohamed

Affiliation

Microbiology department, Medical Research Institute, Alexandria University, Alexandria, Egypt

Email

nancy.attia@alexu.edu.eg

City

Alexandria

Orcid

0000-0002-8738-1007

Volume

5

Article Issue

2

Related Issue

47401

Issue Date

2024-05-01

Receive Date

2024-02-19

Publish Date

2024-05-01

Page Start

636

Page End

650

Print ISSN

2682-4132

Online ISSN

2682-4140

Link

https://mid.journals.ekb.eg/article_345839.html

Detail API

https://mid.journals.ekb.eg/service?article_code=345839

Order

21

Type

Original Article

Type Code

1,157

Publication Type

Journal

Publication Title

Microbes and Infectious Diseases

Publication Link

https://mid.journals.ekb.eg/

MainTitle

Piroxicam repurposing approach as an anti-virulence agent against methicillin resistant <i>Staphylococcus aureus</i> clinical isolates

Details

Type

Article

Created At

25 Dec 2024