Searching for new strategies against polymicrobial biofilm infections: guanylated polymethacrylates kill mixed fungal/bacterial biofilms

Abstract

Objectives: Biofilm-related human infections have high mortality rates due to drug resistance. Cohabitation of diverse microbes in polymicrobial biofilms is common and these infections present additional challenges for treatment compared with monomicrobial biofilms. Here, we address this therapeutic gap by assessing the potential of a new class of antimicrobial agents, guanylated polymethacrylates, in the treatment of polymicrobial biofilms built by two prominent human pathogens, the fungus Candida albicans and the bacterium Staphylococcus aureus. Methods:We used imaging and quantitative methods to test the antibiofilm efficacy of guanylated polymethacrylates, a new class of drugs that structurally mimic antimicrobial peptides. We further compared guanylated polymethacrylates with first-line antistaphylococcal and anti-Candida agents used as combinatorial therapy against polymicrobial biofilms.Results: Guanylated polymethacrylates were highly effective as a sole agent, killing both C. albicans and S. aureus when applied to established polymicrobial biofilms. Furthermore, they outperformed multiple combinations of current antimicrobial drugs, with one of the tested compounds killing 99.98% of S. aureus and 82.2% of C. albicans at a concentration of 128 mg/L. The extracellular biofilm matrix provided protection, increasing the MIC of the polymethacrylates by 2-4-fold when added to planktonic assays. Using the C. albicans bgl2DD mutant, we implicate matrix polysaccharide b-1,3 glucan in the mechanism of protection. Data for two structurally distinct polymers suggest that this mechanism could be minimized through chemical optimization of the polymer structure. Finally, we demonstrate that a potential application for these polymers is in antimicrobial lock therapy.Conclusions: Guanylated polymethacrylates are a promising lead for the development of an effective monotherapy against C. albicans/S. aureus polymicrobial biofilms.

Characteristics of Aspergillus fumigatus in Association with Stenotrophomonas maltophilia in an In Vitro Model of Mixed Biofilm

“…fumigatus cell wall and embedded in the ECM (Fig 3). Most of the published studies on in vitro fungal and bacterial biofilms were performed with yeasts and bacteria [40–42], and very few models worked with filamentous fungi and bacteria, such as A . fumigatus and P .…”

Eradication of Candida albicans persister cell biofilm by the membranotropic peptide gH625

“…Biofilms provide a protected growing, allowing cell survival in a hostile environment and show emergent properties that are not foreseeable from the investigations on planktonic cells 3 . Moreover, biofilms often are not caused by a single-species population of microbes but by mixtures of species of bacteria or fungi and develop on inert surfaces such as medical devices, on living tissues, and also on fragments of dead tissues 4 . Conventional antifungal therapies typically contrast the symptoms of planktonic cells released from the biofilm, but fail to kill the biofilm itself; thus, after cycles of antifungal therapy, biofilm infections are typically recurring until surgically removed 5 .…”

The importance of fungal pathogens and antifungal coatings in medical device infections

“…Polymicrobial biofilms on indwelling medical devices are multifaceted and difficult to treat (Qu et al, 2015). This problem is partly due to the complex interplay between surfaces, bacterial and fungal colonizers, and their biological and physical interactions.…”

“…This problem is partly due to the complex interplay between surfaces, bacterial and fungal colonizers, and their biological and physical interactions. For example, C. albicans hyphae can form a scaffold, which supports and protects S. aureus (Qu et al, 2015). This behaviour is particularly a problem due to the fact that these microbial species are frequently encountered in the clinical setting, and associated with high mortality rates such as that in catheter-related line bloodstream infections (CLBSI) (Sievert et al, 2013).…”