Despite colossal achievements in antibiotic therapy in
recent decades,
drug-resistant pathogens have remained a leading cause of death and
economic loss globally. One such WHO-critical group pathogen is Salmonella. The extensive and inappropriate treatments for Salmonella infections have led from multi-drug resistance
(MDR) to extensive drug resistance (XDR). The synergy between efflux-mediated
systems and outer membrane proteins (OMPs) may favor MDR in Salmonella. Differential expression of the efflux system
and OMPs (influx) and positional mutations are the factors that can
be correlated to the development of drug resistance. Insights into
the mechanism of influx and efflux of antibiotics can aid in developing
a structurally stable molecule that can be proficient at escaping
from the resistance loops in Salmonella. Understanding
the strategic responsibilities and developing policies to address
the surge of drug resistance at the national, regional, and global
levels are the needs of the hour. In this Review, we attempt to aggregate
all the available research findings and delineate the resistance mechanisms
by dissecting the involvement of OMPs and efflux systems. Integrating
major OMPs and the efflux system’s differential expression
and positional mutation in Salmonella may provide
insight into developing strategic therapies for one health application.