Abstract

Antimicrobial resistance (AMR) is a serious and most urgent global threat to human health. AMR is one of today's biggest difficulties in the health system and has the potential to harm people at any stage of life, making it a severe public health issue. There must be fewer antimicrobial medicines available to treat diseases given the rise in antibiotic-resistant organisms. If no new drugs are created or discovered, it is predicted that there won't be any effective antibiotics accessible by 2050. In most cases, Streptococcus increased antibiotic resistance by forming biofilms, which account for around 80 % of all microbial infections in humans. This highlights the need to look for new strategies to manage diseases that are resistant to antibiotics. Therefore, development alternative, biocompatible and high efficacy new strategies are essential to overcome drug resistance. Recently, bacterial derived extracellular vesicles have been applied to tackle infection and reduce the emergence of drug resistance. Therefore, the objective of the current study was designed to assess the antibacterial and antibiofilm potential of outer membrane vesicles (OMVs) derived from Pseudomonas aeruginosa againstStreptococcus mutans. According to the findings of this investigation, the pure P. aeruginosa outer membrane vesicles (PAOMVs) display a size of 100 nm. S. mutans treated with PAOMVs showed significant antibacterial and antibiofilm activity. The mechanistic studies revealed that PAOMVs induce cell death through excessive generation of reactive oxygen species and imbalance of redox leads to lipid peroxidation, decreased level of antioxidant markers including glutathione, superoxide dismutase and catalase. Further this study confirmed that PAOMVs significantly impairs metabolic activity through inhibiting lactate dehydrogenase activity (LDH), adenosine triphosphate (ATP) production, leakage of proteins and sugars. Interestingly, combination of sub-lethal concentrations of PAOMVs and antibiotics enhances cell death and biofilm formation of S. mutans. Altogether, this work, may serve as an important basis for further evaluation of PAOMVs as novel therapeutic agents against bacterial infections.

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