Abstract
Innate immune responses function as a first line of host defense against the development of bacterial infection, and in some cases to preserve the sterility of privileged sites in the human host. Bacteria that enter these sites must counter host responses for colonization. From the host’s perspective, the innate immune system works expeditiously to minimize the bacterial threat before colonization and subsequent dysbiosis. The multifactorial nature of disease further challenges predictions of how each independent variable influences bacterial pathogenesis. From bacterial colonization to infection and through disease, the microenvironments of the host are in constant flux as bacterial and host factors contribute to changes at the host-pathogen interface, with the host attempting to eradicate bacteria and the bacteria fighting to maintain residency. A key component of this innate host response towards bacterial infection is the production of antimicrobial peptides (AMPs). As an early component of the host response, AMPs modulate bacterial load and prevent establishment of infection. Under quiescent conditions, some AMPs are constitutively expressed by the epithelium. Bacterial infection can subsequently induce production of other AMPs in an effort to maintain sterility, or to restrict colonization. As demonstrated in various studies, the absence of a single AMP can influence pathogenesis, highlighting the importance of AMP concentration in maintaining homeostasis. Yet, AMPs can increase bacterial virulence through the co-opting of the peptides or alteration of bacterial virulence gene expression. Further, bacterial factors used to subvert AMPs can modify host microenvironments and alter colonization of the residential flora that principally maintain homeostasis. Thus, the dynamic interplay between host defense peptides and bacterial factors produced to quell peptide activity play a critical role in the progression and outcome of disease.
Highlights
Antimicrobial peptides (AMPs) are widely distributed in animals and plants and are innate host defense peptides that display a broad spectrum of antimicrobial activity against bacteria, viruses, fungi and protozoa [1]
As bacteria navigate through the human host they are confronted with host antimicrobial peptides (AMPs) that threaten their survival (Figure 1)
The colonization of a foreign invader disrupts environmental homeostasis which results in the increased expression of host defense factors, including AMPs
Summary
Antimicrobial peptides (AMPs) are widely distributed in animals and plants and are innate host defense peptides that display a broad spectrum of antimicrobial activity against bacteria, viruses, fungi and protozoa [1]. Other AMPs are cationic, amphipathic molecules of 12 to 50 amino acids in length that are capable of interacting with a bacterial cytoplasmic membrane, comprised primarily of negatively charged phospholipids. Multiple systems have been described that function to counter the initial lethality of rapid ion efflux (e.g., potassium) from the bacterial cell associated with AMP exposure [6,7]. Due to our research focus, we primarily focus the scope of this review to the discussion of the interplay of AMPs with bacterial pathogens. A number of reviews comprehensively characterize AMP expression within various anatomical locations of the human body, knowledge of which is important to consider to more fully understand the multifactorial nature and evolution of disease progression [14,15,16,17,18,19]
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