Document Type

Editorial

Publication Date

9-18-2025

Keywords

glycoside hydrolase, biofilm, treatment, antibiotic, Pseudomonas aeruginosa

Abstract

Background: As of 2022, 80% of all documented microbial infections are biofilm-associated: communities of microorganisms adhered to a surface and enclosed in a complex extracellular polymeric substance (EPS). The EPS acts as a physical barrier protecting the bacteria from antimicrobial agents and host immune responses. To combat this hurdle, the application of glycoside hydrolases (GH) has been investigated due to their ability to cleave particular structural polysaccharides within the EPS, thus breaking down the protective barrier and improving antibiotic clearance. While various studies demonstrate the capacity of GHs to improve antibiotic efficacy against biofilms in combination, there is clear differential success between these treatments depending on the GH and antibiotic chosen. Due to the overlap of GH targets and antibiotic structures, it is imperative to ensure that the antibiotics in combinatorial treatments are not degraded by the GH. Methods: This study aimed to screen the GH α-amylase produced from Aspergillus oryzae (AO) and Bacillus subtilis (BS), combined with various antibiotics from different classes, charges, and mode of actions by determining MICs. against the bacterium Pseudomonas aeruginosa (PA) of 6 antibiotics with or without α-amylase and treat 2-day PA biofilms with antibiotics with or without GHs. Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) stability assays and Differential Scanning Fluorimetry (DSF) were conducted to determine antibiotic and GH degradation as well as antibiotic sequestration. Results: Increased MICs in the presence of GHs as well as decreased antibiotic clearance against 2-day biofilms were suggestive of antibiotic degradation. LC-MS/MS stability assays of tetracycline and ciprofloxacin in the presence and absence of α-amylase further demonstrated the α-amylase-mediated antibiotic sequestration. Differential scanning fluorimetry (DSF) assays confirmed α-amylase-antibiotic interactions. Conclusions: This study suggests that α-amylase is capable of degrading and sequestering a variety of antibiotics, and the degree to which these phenomena occur varies depending upon the source of the GH. As a potential treatment for biofilm-associated infections, it is imperative that the GH + antibiotic combinations are determined compatible prior to clinical use.

Comments

https://doi.org/10.3390/antibiotics14090941

Publisher Attribution

Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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