Analysis of the Antimicrobial and Anti-Biofilm Activity of Natural Compounds and Their Analogues against Staphylococcus aureus Isolates
Mastoor S. Nazim F. Rizwan-ul-Hasan S. Ahmed K. Khan S. Ali S.N. Abidi S.H.
October 2022MDPI
Molecules
2022#27Issue 20
(1) Background: Staphylococcus aureus (S. aureus) is one of the most frequent causes of biofilm-associated infections. With the emergence of antibiotic-resistant, especially methicillin-resistant S. aureus (MRSA), there is an urgent need to discover novel inhibitory compounds against this clinically important pathogen. In this study, we evaluated the antimicrobial and anti-biofilm activity of 11 compounds, including phenyl propenes and phenolic aldehydes, eugenol, ferulic acid, sinapic acid, salicylaldehyde, vanillin, cinnamoyl acid, and aldehydes, against drug-resistant S. aureus isolates. (2) Methods: Thirty-two clinical S. aureus isolates were obtained from Alkhidmat Diagnostic Center and Blood Bank, Karachi, Pakistan, and screened for biofilm-forming potential, and susceptibility/resistance against ciprofloxacin, chloramphenicol, ampicillin, amikacin, cephalothin, clindamycin, streptomycin, and gentamicin using the Kirby-Bauer disk diffusion method. Subsequently, 5 representative clinical isolates were selected and used to test the antimicrobial and anti-biofilm potential of 11 compounds using both qualitative and quantitative assays, followed by qPCR analysis to examine the differences in the expression levels of biofilm-forming genes (ica-A, fnb-B, clf-A and cna) in treated (with natural compounds and their derivatives) and untreated isolates. (3) Results: All isolates were found to be multi-drug resistant and dominant biofilm formers. The individual Minimum Inhibitory Concentration (MIC) of natural compounds and their analogues ranged from 0.75–160 mg/mL. Furthermore, the compounds, Salicylaldehyde (SALI), Vanillin (VAN), α-methyl-trans-cinnamaldehyde (A-MT), and trans-4-nitrocinnamic acid (T4N) exhibited significant (15–92%) biofilm inhibition/reduction percentage capacity at the concentration of 1–10 mg/mL. Gene expression analysis showed that salicylaldehyde, α-methyl-trans-cinnamaldehyde, and α-bromo-trans-cinnamaldehyde resulted in a significant (p < 0.05) downregulation of the expression of ica-A, clf-A, and fnb-A genes compared to the untreated resistant isolate. (4) Conclusions: The natural compounds and their analogues used in this study exhibited significant antimicrobial and anti-biofilm activity against S. aureus. Biofilms persist as the main concern in clinical settings. These compounds may serve as potential candidate drug molecules against biofilm forming S. aureus.
anti-biofilm , antimicrobial , gene expression , natural compounds , Staphylococcus aureus
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Department of Chemistry, Faculty of Science, University of Karachi, Karachi, 75270, Pakistan
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi, 74600, Pakistan
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, 74800, Pakistan
Department of Computer Science, DHA Suffa University, Karachi, 75500, Pakistan
Department of Microbiology, University of Karachi, Karachi, 75270, Pakistan
Department of Biomedical Sciences, Nazarbayev University School of Medicine, Nur-Sultan, 010000, Kazakhstan
Department of Chemistry
Department of Pharmaceutical Chemistry
Department of Biological and Biomedical Sciences
Department of Computer Science
Department of Microbiology
Department of Biomedical Sciences
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