Current research has demonstrated that small cationic amphipathic peptides have strong
potential not only as antimicrobials, but also as antibiofilm agents, immune modulators,
and anti-inflammatories. Although traditionally termed antimicrobial peptides (AMPs)
these additional roles have prompted a shift in terminology to use the broader term
host defense peptides (HDPs) to capture the multi-functional nature of these molecules.
In this review, we critically examined the role of AMPs and HDPs in infectious diseases
and inflammation. It is generally accepted that HDPs are multi-faceted mediators of
a wide range of biological processes, with individual activities dependent on their
polypeptide sequence. In this context, we explore the concept of chemical space as
it applies to HDPs and hypothesize that the various functions and activities of this
class of molecule exist on independent but overlapping activity landscapes. Finally,
we outline several emerging functions and roles of HDPs and highlight how an improved
understanding of these processes can potentially be leveraged to more fully realize
the therapeutic promise of HDPs.