Combating bacterial resistance by combination of antibiotics with antimicrobial peptides

Abstract

The overuse of antibiotics in the healthcare and agricultural industries has led to the worldwide spread of bacterial resistance. The recent emergence of multidrug resistant (MDR) bacteria has resulted in a call for the development of novel strategies to address this global issue. Research on a diverse range of antimicrobial peptides (AMPs) has shown promising activity against several resistant strains. Increased understanding of the mode of action of AMPs has shown similarity and complementarity to conventional antibiotics and the combination of both has led to synergistic effects in some cases. Combination therapy has been widely used to combat MDR bacterial infections and the recent focus on their application with AMPs may allow antibiotics to be effective against resistant bacterial strains. By conjugation of an antibiotic onto an AMP, a compound may be produced with possibly greater activity and with reduced side-effects and toxicity. The AMP in these conjugates may also act as a unique adjuvant for the antibiotic by disrupting the resistance mechanisms used by bacteria thus allowing the antibiotic to once again be effective. This mini-review outlines some of the current and past work in combining AMPs with conventional antibiotics as strategies to address bacterial resistance.

(Re)Defining the Proline-Rich Antimicrobial Peptide Family and the Identification of Putative New Members

“…While its intracellular target and mode of action have yet to be identified, (Rabel et al, 2004 ), given the similarity to known PrAMPs and its synergistic activity, attacin-C may be a DnaK inhibitor despite not appearing to be membrane permeable. At this point, without confirmed antimicrobial activity, attacin-C may be best considered as an AMP adjuvant (Sheard et al, 2019 ).…”

“…Antimicrobial peptides (AMPs) are a well-known class of naturally occurring compounds with potent bactericidal activity. They typically exert their antimicrobial efficacy via membrane disruption leading to lysis (Sheard et al, 2019 ). However, a subclass known as proline-rich AMPs (PrAMPs) are membrane permeable and non-lytic (Li et al, 2014 ).…”

A Bifunctional Peptide Conjugate That Controls Infections of Erwinia amylovora in Pear Plants

“…Studies on antimicrobial peptides are almost solely focused on the use of individual peptides. However, another attractive approach relies on mixtures of different peptides or mixtures of peptides and conventional antibiotics [ 18 , 44 ]. Concerning the combination of two antimicrobial peptides, these mixtures have been reported to cause a higher antimicrobial effect than the individual components [ 18 , 45 , 46 , 47 , 48 ].…”

Nuclear Magnetic Resonance Study of the Peptide FRANCESSEPAROVIC

“…[2b,7] Many MAPs are either derived from naturally occurring amino acid sequences or by combining these sequences with other molecules to optimise a specific therapeutic property. [8] De novo design is another possibility whereby the peptide sequence is not mimicking a naturally occurring amino acid sequence but instead is built based on rational design inputs. In this work, we have shown for the first time that the de novo FS peptide is membrane active and thus a potential template for MAP studies.…”