AMPs as Anti-biofilm Agents for Human Therapy and Prophylaxis

Caprine Bactenecins as Promising Tools for Developing New Antimicrobial and Antitumor Drugs

“…We also observed potentially useful effects of the studied peptides on bacterial biofilm formation, one of the major bacterial strategies to evade unfriendly environmental factors, including the action of various antimicrobial compounds and of immune system of the host (de la Fuente-Nuńěz et al, 2016;Chen et al, 2018;Shahrour et al, 2019). Well over a half (65%-80% by different assessments) of clinical cases related with bacterial infections are associated with biofilms (Costerton et al, 1999;Jorge et al, 2012;Pletzer and Hancock, 2016).…”

“…In this mode of growth bacterial cells are protected by a dense extracellular matrix, restricting their accessibility for immune effectors and clinically used antimicrobials alike. Moreover, persister cells existing within a biofilm are metabolically inactive, so they pose a serious challenge for conventional antibiotics (Jorge et al, 2012;Shahrour et al, 2019). For a little more than a decade, AMPs have been acknowledged as a promising source of antibiofilm agents as well as of antibacterials, although only a small fraction of identified AMPs have been adequately studied in this particular aspect to date (Dostert et al, 2019).…”

“…It was shown that various AMPs on their own not only eliminate planktonic bacteria, but also weaken the primary adhesion of bacterial cells to the surface, and within the established biofilms can impair the interaction of the elements of extracellular matrix and embedded bacterial cells. In addition, more specific mechanisms were revealed for a number of peptides demonstrating strong antibiofilm capabilities: they can modulate the motility of bacterial cells; affect the quorum sensing signaling; impede the work of the (p)ppGpp alarmone and, by extension, interfere with bacterial stringent response, and reduce the synthesis of various matrix elements or lead to their degradation (Pletzer and Hancock, 2016;Yasir et al, 2018;Casciaro et al, 2019;Shahrour et al, 2019).…”

Antimicrobial Susceptibility Testing of Antimicrobial Peptides to Better Predict Efficacy

“…A number of mechanisms are responsible for biofilm antibiotic-tolerance including; (1) reduced diffusion of antibiotics through the biofilm matrix, (2) sequestration of antibiotics by the biofilm matrix; (3) presence of slow-growing and persister cells (see below) refractory to antibiotics targeting bacterial metabolism; and (4) increased exchange of antibiotic resistance genes on mobile genetic elements by cells in close proximity (Stewart and Costerton, 2001 ; Hall and Mah, 2017 ; Orazi and O'Toole, 2019 ). The potential role of AMP as therapeutics to treat biofilm infections has received significantly more attention than activity vs. spores, persister cells or SCV and has been the subject of several review articles in the last few years (Batoni et al, 2016 ; de la Fuente-Nunez et al, 2016 ; Pletzer and Hancock, 2016 ; Delattin et al, 2017 ; Grassi et al, 2017b ; van Dijck et al, 2018 ; Von Borowski et al, 2018 ; Yasir et al, 2018 ; Shahrour et al, 2019 ). A detailed analysis of the potential role of AMP in the treatment of biofilm infections is beyond the scope of this manuscript, but some key points with respect to AST will be addressed in the following paragraphs.…”

Strategies in Translating the Therapeutic Potentials of Host Defense Peptides

“…Additionally, HDPs could also kill bacteria via inhibition of macromolecules that are involved in the biosynthesis of the surface membrane, and components of metabolic organelles (11,12). Such unique mechanism of action accounts for the rapid and broad-spectrum antimicrobial action and the low risk of developing AMR as modification of the entire microorganisms' anionic membrane incurs a substantially higher fitness cost when compared to alteration of a particular binding site targeted by the conventional antibiotics (e.g., alteration in the 30S subunit inhibits the action of aminoglycosides) (13).…”