This study aimed to evaluate the effect of reserpine, a plant-derived indole-alkaloid, against Pseudomonas aeruginosa PAO1 biofilms. The anti-biofilm activity of reserpine was evaluated by crystal violet staining, MTT assay, confocal laser scanning microscopy and scanning electron microscopy. Reserpine effects were also assessed by qRT-PCR of quorum sensing (QS)-regulated genes and biochemical quantification of the QS-mediated virulence factors pyocyanin, rhamnolipids, proteases and elastases. Reserpine reduced biofilm formation, cell motility, virulence factor production, and QS-controlled gene expression. Additionally, molecular docking analysis for AHL synthase LasI and QS transcriptional regulators LasR/MvfR revealed a plausible molecular mechanisms of reserpine QS inhibition. These findings provide insights into the underlying mode of action of reserpine, which may be useful in the development of new drugs against biofilm-related infections.
Background:
It was apparent by the end of 1980s that the victory against the threats of bacterial pathogens on public health was an illusion, with the faster development of resistant strains than the discovery of new drugs. As a consequence, the remedial services were in the backfoot position of being on the losing side of this never-ending evolutionary war. The quest for new antibiotics to overcome resistance problems has long been a top research priority for the researchers and the pharmaceutical industry. However, the resistance problems are remaining due to the abrupt misuse of antibiotics by common people, which has immensely worsened the scenario by disseminating antibiotic-resistant bacterial strains around the world.
Objective:
Thus, immediate action is needed to measure emerging and re-emerging microbial diseases having new resistance mechanisms and to manage their rapid spread among the common public by means of novel alternative metabolites.
Conclusion:
Antimicrobial peptides (AMPs) are short, cationic peptides evolved in a wide range of living organisms and serve as the essential part of host innate immunity. For humans, these effector molecules either can directly kill the foreign microbes or modulate the host immune systems so that human body could make some resistance against the microbial infections. In this review, we discuss their history, structural classifications, modes of action, and explain their biological roles as anti-infective agents. We also scrutinize their clinical potentiality, current limitations in various developmental stages and strategies to overcome for their successful clinical applications.
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