Host-Bacterial Interactions: Outcomes of Antimicrobial Peptide Applications

Abstract

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.

Keywords: antimicrobial peptides; antimicrobial resistance; bacterial membrane; quorum sensing; secreting system.

Figure 1

Different types of secretion systems. IM: Inner membrane. OM: Outer membrane. ATP: Adenosine triphosphate. ATPase: Adenosine triphosphatase. ADP: Adenosine diphosphate. MFP: Membrane fusion protein found in the T1SS. OMP: Outer membrane protein.

Figure 2

QS systems in Gram-negative and Gram-positive bacteria. Left figure (A): Gram-negative bacteria secrete acyl-homoserine lactones (AHLs) as autoinducers, which are synthesized by Luxl and then pass through the bacterial membrane into the external environment. Once the AHLs reach a threshold level, they activate intracellular LuxR to activate target gene expression. Right figure (B): Gram-positive bacteria secrete autoinduction peptides (AIPs), which are synthesized by AIPs synthase and then pass through the bacterial membrane into the external environment. Once the AIPs reach a threshold level. This is detected by a specific protein, histidine kinases, and activates the intracellular regulator. The response regulator leads to increased expression of the target gene.

Figure 3

General principle of the QS system. Left figure: Each species begins to secrete autoinducers into the external environment, and the population density increases. Right figure: Increased rate of autoinducer release to form biofilm due to gene expression.

Figure 4

Mechanism of AMPs in membrane targeting.