Pro-rich Antimicrobial Peptides from Animals: Structure, Biological Functions and Mechanism of Action

Abstract

Pro-rich antimicrobial peptides are a group of linear peptides of innate immunity isolated from mammals and invertebrates, and characterised by a high content of proline residues (up to 50%). Members of this group are predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism, at variance with the majority of the known antimicrobial peptides. Evidence is accumulating that the Pro-rich peptides enter the cells without membrane lysis and, once in the cytoplasm, bind to, and inhibit the activity of specific molecular targets essential to bacterial growth, thereby causing cell death. This mode of action makes these peptides suitable for drug development efforts. In addition to antibacterial action, PR-39, one of the better characterised Pro-rich peptides from mammals, exerts other potentially exploitable biological activities, such as induction of syndecan expression in mesenchymal cells and inhibition of the NADPH oxidase activity of neutrophils, suggesting a role of this peptide in wound repair and inflammation. PR-39 also exerts a protective effect in various animal models of ischemia-reperfusion injury, preventing the post-ischemic oxidant production, and is a potent inducer of angiogenesis both in vitro and in vivo. Although the physiological relevance of all these effects has not yet been established, the above observations underscore the therapeutic potential of this peptide in a number of complex processes such as inflammation, wound repair, ischemia-reperfusion injury, and angiogenesis.

Comparative structural modeling and inference of conserved protein classes in Drosophila seminal fluid

“…Additionally, three peptide-sized Acps (CG9029, CG9074, and CG14560) have a high content of proline residues (25.8%, 16.7%, and 24.6%, respectively). Models for these three peptides could not be generated, but their proline richness is consistent with an antimicrobial role because proline-rich peptides are found in many organisms' innate immune responses (46).…”

ChBac3.4: A Novel Proline-Rich Antimicrobial Peptide from Goat Leukocytes

“…Their antimicrobial action is believed to occur via non-lytic mechanism and directed to intracellular targets (Gennaro et al 2002;Otvos 2002), and a putative transporter has been recently identified in E. coli as the membrane protein sbmA (Mattiuzzo et al 2007). However, at higher concentrations some of them may also act by damaging bacterial membranes (Podda et al 2006).…”

Chimeric Antimicrobial Peptides Exhibit Multiple Modes of Action

“…However the moderate clinical success and therapeutic index of broad-spectrum antimicrobial peptides has made the pharmaceutical industry less than enthusiastic about peptide antibiotics, even if new indications, such as immune stimulatory activities may give a second life to these lead molecules (Bowdish et al 2004). Interest has slowly shifted to peptides acting on intracellular bacterial targets although inactivation of bacterial macromolecules can restrict the pool of peptide-susceptible bacterial strains due to potential sequence modifications of the target proteins (Gennaro et al 2002). As attractive as the inactivation of intracellular macromolecules is, the current report documents that penetration into bacterial cells is still the rate-limiting step.…”