Redox Active Antimicrobial Peptides in Controlling Growth of Microorganisms at Body Barriers

Abstract

Epithelia in the skin, gut and other environmentally exposed organs display a variety of mechanisms to control microbial communities and limit potential pathogenic microbial invasion. Naturally occurring antimicrobial proteins/peptides and their synthetic derivatives (here collectively referred to as AMPs) reinforce the antimicrobial barrier function of epithelial cells. Understanding how these AMPs are functionally regulated may be important for new therapeutic approaches to combat microbial infections. Some AMPs are subject to redox-dependent regulation. This review aims to: (i) explore cysteine-based redox active AMPs in skin and intestine; (ii) discuss casual links between various redox environments of these barrier tissues and the ability of AMPs to control cutaneous and intestinal microbes; (iii) highlight how bacteria, through intrinsic mechanisms, can influence the bactericidal potential of redox-sensitive AMPs.

Significance of Endogenous Antimicrobial Peptides on the Health of Food Animals

“…The antimicrobial activities of endogenous AMPs include inactivation of pathogenic microbes, reinforcing the antimicrobial barrier function of epithelial cells particularly in the gut, and linking innate immunity to adaptive immunity ( 76 , 77 ). The cationic nature of endogenous AMPs facilitate their ability to exert antimicrobial effect(s) on pathogens.…”

“…Furthermore, the presence of thioredoxin, a redox protein present at the intestinal epithelial surface, is known to facilitate the antimicrobial activity of AMPs ( 86 ). A recent report by has also suggested that redox active AMPs can undergo reversible oxidation after interaction with some electron transport chain proteins and their products, or interaction with the periplasmic redox system of Gram-negative bacteria ( 77 ). Further research is required to identify molecular-based strategies that will exploit the reversible oxidation state of endogenous AMPs, for the synthesis of AMPs that will have improved stability in the gut mucosa and other epithelial membranes.…”

Chemerin Regulates Epithelial Barrier Function of Mammary Glands in Dairy Cows

“…Chemerin, which was originally identified as a chemoattractant protein for antigen-presenting cells [ 4 ], is currently recognized to have antimicrobial properties [ 5 ]. This protein has an inhibitory effect on commensal pathogen activity, including Escherichia coli and Staphylococcus aureus which are the major mastitis-causing pathogens [ 6 , 7 ].…”

Rare by Natural Selection: Tunable Disulfide-bonded Supramolecular Antimicrobials Peptides

“…Furthermore, secretion of reducing and oxidizing factors can regulate the activity of cysteine-containing AMPs that form disulfide bonds essential for their folding and activity [16][17][18][19][20][21][22][23][24][25][26][27][28] . For instance, pro-inflammatory processes involve oxidative stress through elevating reactive oxygen species (ROS) concentrations [23][24][25]29 . In parallel, some pathogens can promote and express reducing factors that diffuse the oxidativedependent processes of inflammation and affect the activity of cysteine-rich AMPs 25,26,30 .…”

“…Paradoxically, in the presence of elevated concentrations of a reduction agent, the antibiotic activity of the human b-defensin 3, which is a cysteine-rich AMP, decreased, while that of bdefensin 1 increased, indicating distinct structure-function relationships and physiological regulation of antimicrobial peptides via reductive pathways 28,29,31,32 .…”