Unraveling the mechanistic insights of sophorolipid-capped gold nanoparticle-induced cell death in Vibrio cholerae

Cholera is one of the leading causes of mortality and morbidity worldwide. The treatment of cholera includes rehydration therapy, often combined with the administration of antibiotics (in severe cases). With the emergence and rapid spread of antimicrobial resistance, such microbial pathogens have become a compelling medical problem and a global threat. To combat the resistance to antibiotics, there is an urgent need for the discovery of novel and potent antimicrobial agents. The discovery of antimicrobial nanoparticles as an alternative to the existing antimicrobial regime has increased the hope for its use as one of the most promising tools against an array of microbial pathogens, including multidrug-resistant bacteria. Our recent report demonstrated that sophorolipid-capped gold nanoparticles (AuNPs-SL) exhibit potent antibacterial activity against Vibrio cholerae; however, the killing mechanism remained obscure. Metal nanoparticle-mediated killing of microbes occurs through non-specific mechanisms. To develop antimicrobial nanoparticles with better efficacy, knowledge of their specific mechanism of action is essential. In this work, we deduced the mechanistic insights of AuNPs-SL mediated cell death of V. cholerae. We observed that AuNPs-SL treatment evokes reactive oxygen species (ROS) formation. The surge in the ROS level triggers the overexpression of ROS-responsive genes, depolarization of the membrane, change in membrane permeability and leakage of intracellular proteins and DNA, depletion of ATP levels in the cell, DNA damage, and subsequent cell death. This study shows the possibility of use of AuNPs-SL as an alternative potential antimicrobial agent.