Phytophenolic derivatives as potential ameliorative agents for microbial superbugs: mechanisms of action, cellular pathways and synergistic selectivity with chemotherapeutics

The increasing resistance of microbes to standard antibiotics is a major concern in the management of contagious infections and has led to an unprecedented increase in mortality rates. The identification of the microbial "superbugs" responsible for hospital-acquired pathogenic maladies has prompted a significant amount of research in recent years, with the hope of revealing potentially beneficial answers to the ensuing health challenges by leveraging on ethnomedicinal remedies. The antibacterial activity of phytophenols was demonstrated against a wide range of pathogens, including those that have developed resistance to conventional antibiotics via their aligning resistance mechanisms. Here, we have recapitulated the most important bacterial drug resistance pathways and elucidated the dynamics of the phytophenols in Thymus vulgaris, Piper nigrum, Nigella sativa, and Annona muricata in potentially hindering and disrupting the antibiotic resistance dynamics of microbial superbugs implicated in nosocomial infections. The in-vitro antibacterial activity of phytophenolic substances and their synergistic selectivity with chemotherapeutics validated an efficacy in combating antibiotic resistance mechanisms in microbial superbugs in-vitro. The mechanisms of antibiotic resistance synthesis and polyphenolic interactions with microbial cellular pathways via antioxidant properties showed promising prospects in ameliorating the public health threat posed antibiotic-resistant superbugs. The major challenge in developing new phytochemicals with public health importance for microbial "superbugs" is the replication of in-vitro explorations via in-vivo experimentation and, ultimately, human medical testing for clinical trial. However, additional research is needed to confirm the activity pathways and stability of these phytoactive compounds, as a number of these phytoactives exhibit synergistic antimicrobial effects with chemotherapeutics.