AI Article Synopsis

  • The increasing issue of multidrug resistance (MDR) in pathogenic bacteria like Staphylococcus aureus has prompted the search for new treatment methods, including FDA-drug repurposing.
  • Ambroxol was tested against clinical MDR S. aureus isolates and showed effective antibacterial activity, with concentrations needed to inhibit growth between 0.75 to 1.5 mg/mL, and also disrupted biofilm formation in about 42% of the isolates.
  • In vivo studies demonstrated ambroxol's ability to enhance skin tissue healing in S. aureus infected burn injuries by reducing bacterial presence and inflammation, with further investigations suggesting its action may involve binding to several targets in the bacterium.

Article Abstract

It is critical to find novel therapeutic approaches owing to the dissemination of multidrug resistance (MDR) in pathogenic bacteria, particularly Staphylococcus aureus. FDA-drug repurposing is an important therapeutic tactic to fight MDR bacteria. Here, we inspected the antibacterial activity of ambroxol against clinical MDR S. aureus isolates. Using the broth microdilution method, ambroxol revealed minimum inhibitory concentrations (MICs) of 0.75 to 1.5 mg/mL. Also, it revealed antibiofilm action on 42.17% of the isolates by crystal violet assay. A scanning electron microscope was employed to study the antibiofilm action of ambroxol. It revealed that the association between the cells was interrupted by ambroxol, and the biofilm construction was devastated. Moreover, qRT-PCR was utilized to elucidate the consequence of ambroxol on the gene expression of efflux and biofilm. Remarkably, ambroxol has downregulated the expression of cna, fnb A, ica, nor A, nor B genes. Ambroxol's in vivo antibacterial action was investigated using S. aureus infected burn infection. Interestingly, ambroxol has improved the histological features of the skin tissues, significantly diminished the bacterial burden, and increased the wound healing percentage. Also, it revealed a significant reduction in the immunohistochemical staining of tumor necrosis factor-alpha. Finally, the in silico investigations were performed to elucidate the potential of ambroxol on five possible targets of S. aureus. Ambroxol showed good affinities on the five investigated targets in S. aureus, with CrtM being the highest, proposing its probable role in the mechanisms for ambroxol's action on S. aureus.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606196PMC
http://dx.doi.org/10.1186/s12866-024-03666-xDOI Listing

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