The bacterial membrane is part of a secretion system which plays an integral role to secrete proteins responsible for cell viability and pathogenicity; pathogenic bacteria, for example, secrete virulence factors and other membrane-associated proteins to invade the host cells through various types of secretion systems (Type I to Type IX). The bacterial membrane can also mediate microbial communities’ communication through quorum sensing (QS), by secreting auto-stimulants to coordinate gene expression. QS plays an important role in regulating various physiological processes, including bacterial biofilm formation while providing increased virulence, subsequently leading to antimicrobial resistance. Multi-drug resistant (MDR) bacteria have emerged as a threat to global health, and various strategies targeting QS and biofilm formation have been explored by researchers worldwide. Since the bacterial secretion systems play such a crucial role in host–bacterial interactions, this review intends to outline current understanding of bacterial membrane systems, which may provide new insights for designing approaches aimed at antimicrobials discovery. Various mechanisms pertaining interaction of the bacterial membrane with host cells and antimicrobial agents will be highlighted, as well as the evolution of bacterial membranes in evasion of antimicrobial agents. Finally, the use of antimicrobial peptides (AMPs) as a cellular device for bacterial secretion systems will be discussed as emerging potential candidates for the treatment of multidrug resistance infections.

Multidrug resistance (MDR) has become an increasing threat to global health because bacteria can develop resistance to antibiotics over time. Scientists worldwide are searching for new approaches that go beyond traditional antibiotic discovery and development pipelines. Advances in genomics, however, opened up an unexplored therapeutic opportunity for the discovery of new antibacterial agents. Genomic approaches have been used to discover several novel antibiotics that target critical processes for bacterial growth and survival, including histidine kinases (HKs), LpxC, FabI, peptide deformylase (PDF), and aminoacyl-tRNA synthetases (AaRS). In this review, we will discuss the use of microbial genomics in the search for innovative and promising drug targets as well as the mechanisms of action for novel antimicrobial agents. We will also discuss future directions on how the utilization of the microbial genomics approach could improve the odds of antibiotic development having a more successful outcome.