EFFLUX PUMP INHIBITORY ACTIVITY OF BERBERINE AND PALMATINE AND THEIR SYNERGISTIC ACTIVITY WITH CIPROFLOXACIN IN MULTIDRUG-RESISTANT STAPHYLOCOCCUS AUREUS FROM INFECTED WOUNDS IN SHAHROUD, IRAN

Authors: Seyed Sajjad Khoramrooz, Seyed Sajjad Aghayan, Davood Darban-Sarokhalil, Mohammad Taghi Rahimi, Hamed Tahmasebi, Mehdi Mirzaree
Journal: Journal of Animal and Plant Sciences (JAPS)
ISSN: 1018-7081 (Print), 2309-8694 (Online)
Volume: 35  Issue: 4  Pages: 1112-1126
Year: 2025
DOI: https://doi.org/10.36899/JAPS.2025.4.0095
URL: https://doi.org/https://doi.org/10.36899/JAPS.2025.4.0095
Publisher: Pakistan Agricultural Scientists Forum

Abstract:
<p>Increased efflux due to over-expression of efflux pump is a common mechanism of multidrug resistance in&nbsp;<em>Staphylococcus aureus</em>. More recognized resistance mechanisms have eclipsed the contribution of efflux pumps to resistance in S. aureus. This research aimed to assess the efficacy of combining berberine and palmatine with ciprofloxacin in treating&nbsp;<em>S. aureus</em>&nbsp;infections obtained from wounds. The microtiter plate tests were used to study the antimicrobial susceptibility pattern, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of ciprofloxacin, berberine, and palmatine. The EP inhibition and accumulation assays were performed with a combination of plant extract and ciprofloxacin. Eighty (80)&nbsp;<em>S. aureus</em>&nbsp;isolates were collected from the burn infections. Out of 80 isolates, 76.25 % were resistant to&nbsp;<a href="http://www.mastgrp.com/catalogue_products_fulldetails.asp?SubProduct_Type=144&amp;cat=1&amp;product=CX5C">cloxacillin</a>&nbsp;and erythromycin. Also, 1.25 % of&nbsp;<em>S. aureus</em>&nbsp;isolates were resistant to clindamycin and&nbsp;<a href="http://www.mastgrp.com/catalogue_products_fulldetails.asp?SubProduct_Type=144&amp;cat=1&amp;product=TEC30C">teicoplanin</a>. Likewise, 65%, 21.25%, and 1.25% were considered MDR, XDR, and PDR strains, and 90% of&nbsp;<em>S. aureus</em>&nbsp;isolates were MRSA. The&nbsp;<em>norA</em>,&nbsp;<em>norB</em>,&nbsp;<em>norC,&nbsp;</em>and<em>&nbsp;mecA</em>&nbsp;were reported in 67.5%, 91.25 %, and 90 % of isolates, respectively. Based on the ciprofloxacin-resistant strains (72.5%), the MIC range of berberine and palmatine extracts in 27 isolates (33.7%) was 16 &micro;g/mL to 64 &micro;g/mL. After the combination, the MIC of ciprofloxacin was reduced more than 10-fold in resistant strains. A significant relationship was reported between the combination of plant extract and ciprofloxacin in resistant isolates (p&lt;0.05). The best results of combining berberine, palmatine extract, and ciprofloxacin were observed in MDR, XDR, and PDR strains (p&lt;0.001). Antimicrobial results of berberine and palmatine extracts against&nbsp;<em>S. aureus</em> were observed; however, clinical trials are necessary to confirm the efficiency of these extracts. We reported that combining berberine and palmatine with ciprofloxacin might reduce treatment failure due to EP overexpression.</p>

Keywords: Staphylococcus aureus, Anti-MRSA plants, Multi-Drug Resistant, Antibiotic resistance