Proline-rich antimicrobial peptides: potential therapeutics against antibiotic-resistant bacteria

Abstract

The increasing resistance of pathogens to antibiotics causes a huge clinical burden that places great demands on academic researchers and the pharmaceutical industry for resolution. Antimicrobial peptides, part of native host defense, have emerged as novel potential antibiotic alternatives. Among the different classes of antimicrobial peptides, proline-rich antimicrobial peptides, predominantly sourced from insects, have been extensively investigated to study their specific modes of action. In this review, we focus on recent developments in these peptides. They show a variety of modes of actions, including mechanism shift at high concentration, non-lytic mechanisms, as well as possessing different intracellular targets and lipopolysaccharide binding activity. Furthermore, proline-rich antimicrobial peptides display the ability to not only modulate the immune system via cytokine activity or angiogenesis but also possess properties of penetrating cell membranes and crossing the blood brain barrier suggesting a role as potential novel carriers. Ongoing studies of these peptides will likely lead to the development of more potent antimicrobial peptides that may serve as important additions to the armoury of agents against bacterial infection and drug delivery.

The Mechanism of Killing by the Proline-Rich Peptide Bac7(1–35) against Clinical Strains of Pseudomonas aeruginosa Differs from That against Other Gram-Negative Bacteria

“…Bac7 and its BODIPY fluorescently labeled derivative [Bac7 -BY] were prepared as previously described (14). Bac5(1-31) and BMAP27 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) were chemically synthesized as previously described (41). Apidaecin 137 and oncocin 112 were generously provided by Ralf Hoffmann (13,42).…”

“…The group of proline-rich peptides (PR-AMPs) is the best known example of these intracellular-acting peptides (5,6). Some of them have been identified in mammal neutrophils (7), whereas others have been found in hemolymph of insects and crustaceans (8).…”

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

“…In other settings, structurally related proteins have antibacterial activity. 76 The down-regulated genes included CGA, PSG1, and SHOOM3, which is essential for normal kidney development in mice. 77 We also found decreased expression of an mRNA that encodes ELOVL2, which is involved in the extension of long-chain fatty acids.…”

Multimerization of a Proline-Rich Antimicrobial Peptide, Chex-Arg20, Alters Its Mechanism of Interaction with the Escherichia coli Membrane

“…Among the various types of AMPs, proline-rich AMPs (PrAMPs), which are typically found in insects and higher-order animals, show particular efficacy against systemic infections caused by Gram-negative bacteria. They display multimodal in vivo activity that include a combination of cell-penetrating capacity, targeting of several intracellular components including the 70-kDa bacterial heat shock protein DnaK causing interference with bacterial protein folding, and immunomodulatory activity (Li et al, 2014). Importantly, the PrAMPs, apidaecins, Bac7, and oncosins, were recently shown to bind with nanomolar dissociation constants to the 70S ribosome, leading to blockade of protein biosynthesis (Krizsan et al, 2014;Mardirossian et al, 2014).…”