Abstract
Nowadays, antibiotic resistance has become increasingly common, triggering a global health crisis, immediately needing alternative, including repurposed drugs with potent bactericidal effects. We demonstrated that chlorpromazine aqueous solutions exposed to laser radiation exhibited visible activity against various microorganisms. The aim of this study was to investigate the quantitative antimicrobial activity of chlorpromazine in non-irradiated and 4-h laser irradiated form. Also, we examined the effect of both solutions impregnated on a cotton patch, cannula, and urinary catheter against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa and Escherichia coli. In all experimental versions, the chlorpromazine antimicrobial activity was enhanced by laser exposure. Besides the experimental results, the in silico analyses using molecular docking proved that the improved antimicrobial activity of the irradiated compound was a result of the combined action of the photoproducts on the biological target (s). Our results show that laser radiation could alter the molecular structure of various drugs and their effects, proving to be a promising strategy to halt antibiotic resistance, by repurposing current medicines for new antimicrobial strategies, thereby decreasing the costs and time for the development of more efficient drugs.
Highlights
Nowadays, antibiotic resistant bacteria are a global public issue related to extended illness and high mortality rates [1,2]
The increasing rates of antibiotic resistance and the urgent demand for novel therapeutic strategies lead to drug repurposing for fighting biofilm-associated infections
Chlorpromazine is not an antimicrobial drug, it does not act on the molecular targets of classic antibacterial agents; it may not affect the emergence of antibacterial resistance
Summary
Antibiotic resistant bacteria are a global public issue related to extended illness and high mortality rates [1,2]. Bacteria can adhere to abiotic or biotic surfaces, forming microbial biofilms that are more resistant both to antibiotic treatments and to host immune effectors [3,4]. In contrast to their planktonic counterparts, biofilm embedded cells are usually heterogeneous, both in term of taxonomy and physiology, and are found in close proximity to each other, being covered with a protective extracellular matrix secreted by themselves [5,6]. The largest growth in infection rates was observed in diarrhea due to toxigenic Clostridium difficile, an ailment linked to antibiotic use. The increased prevalence of antibiotic-associated diarrhea is but one of the complications that can appear from increased antibiotic use; an even greater threat comes from increasing antimicrobial resistance of many nosocomial pathogens [7]
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