Therapeutic Potential of Antimicrobial Peptides in Polymicrobial Biofilm-Associated Infections

Abstract

It is widely recognized that many chronic infections of the human body have a polymicrobial etiology. These include diabetic foot ulcer infections, lung infections in cystic fibrosis patients, periodontitis, otitis, urinary tract infections and even a proportion of systemic infections. The treatment of mixed infections poses serious challenges in the clinic. First, polymicrobial communities of microorganisms often organize themselves as biofilms that are notoriously recalcitrant to antimicrobial therapy and clearance by the host immune system. Secondly, a plethora of interactions among community members may affect the expression of virulence factors and the susceptibility to antimicrobials of individual species in the community. Therefore, new strategies able to target multiple pathogens in mixed populations need to be urgently developed and evaluated. In this regard, antimicrobial or host defense peptides (AMPs) deserve particular attention as they are endowed with many favorable features that may serve to this end. The aim of the present review is to offer a comprehensive and updated overview of studies addressing the therapeutic potential of AMPs in mixed infections, highlighting the opportunities offered by this class of antimicrobials in the fight against polymicrobial infections, but also the limits that may arise in their use for this type of application.

Keywords: Pseudomonas aeruginosa; Staphylococcus aureus; antimicrobial peptides; biofilms; host defense peptides; lung infections; mixed infections; polymicrobial infections; wound infections.

Figure 1

Effects of S. aureus–P. aeruginosa mixed infection on resistance and virulence as compared to single-species biofilms. Some of the best characterized interactions that occur between the two species in mixed biofilms are shown. See text for details. HQNO: 4-Hydroxy-2-Heptylquinoline N-Oxide; SCV: small colony variant; AI-2: autoinducer 2; GlcNAc: N-acetyl glucosamine, a component of bacterial peptidoglycan.

Figure 2

Formation stages of a polymicrobial biofilm in a skin wound taken as an example of mixed biofilm-associated infections. The red boxes show the multiple mechanisms of action proposed for the antibiofilm activity of AMPs. AMP: Antimicrobial peptide; QS: Quorum sensing; EPS: Extracellular polymeric substances.

Figure 3

Main steps of the preparation of the ALG/HA/COL-Tet213 wound dressings. (a) The AMP Tet213-conjugated ALG/HA/COL wound dressings were prepared using the chemical reaction between the carboxyl groups and the amino groups on ALG, COL, HA, and Tet213; EDC: 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide; NHS: N-hydroxysuccinimide. (b) Multiple biological activities of the Tet213-conjugated ALG/HA/COL. Reproduced from Ref. [53] with permission, with slight modifications.