Catalase Protects Biofilm of Staphylococcus aureus against Daptomycin Activity.

Cristina El Haj,Peter Østrup Jensen,Karen Leth Nielsen,Thomas Bjarnsholt,Mads Lichtenberg

doi:10.3390/antibiotics10050511

Cristina El Haj, Peter Østrup Jensen + Show 3 more

Open Access

https://doi.org/10.3390/antibiotics10050511

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Journal: Antibiotics	Publication Date: Apr 30, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: University of Copenhagen, Rigshospitalet

Abstract

Daptomycin is recommended for the treatment of Staphylococcus aureus infections due to its bactericidal activity. However, its mechanism of action is poorly understood. The involvement of reactive oxygen species (ROS) in the bactericidal activity of daptomycin has been proved against planktonic S. aureus, but not against the biofilm of S. aureus. Therefore, we evaluated if ROS contributes to the effect of daptomycin against biofilm of S. aureus. Biofilms of wild type, catalase deficient and daptomycin-resistant S. aureus strains were grown in microtiter-plates. After three days, the biofilms were exposed to daptomycin with or without thiourea in the presence of a ROS indicator. After overnight incubation, the amount of ROS and the percentage of surviving bacteria were determined. The bacterial survival was higher and the amount of ROS was lower in the wild type than in the catalase deficient biofilm, demonstrating a protective effect of catalase against daptomycin. The induction of cytotoxic ROS formation by daptomycin was verified by the addition of thiourea, which reduced the amount of ROS and protected the wild type biofilm against high concentrations of daptomycin. Accordingly, only the highest concentration of daptomycin reduced the bacterial survival and increased the ROS formation in the resistant biofilm. In conclusion, daptomycin induced the production of cytotoxic levels of endogenous ROS in S. aureus biofilm and the presence of catalase protected the biofilm against the lethality of the induced ROS.

Highlights

Biofilm-related infections have become a major clinical challenge
We compared the effect of catalase on daptomycin daptomycin treatment using the wild type S. aureus strain (SH1000) and a S. aureus strain treatment using the wild type S. aureus strain (SH1000) and a S. aureus strain with deficient with deficient catalase activity (KO)
We found that catalase deficiency was associated with significantly with significantly decreased survival during daptomycin treatment, demonstrating that decreased survival during daptomycin treatment, demonstrating that catalase protects catalase protects biofilm of S. aureus against daptomycin (Figure 2)

Summary

Introduction

Biofilm-related infections have become a major clinical challenge. Bacterial biofilmrelated infections exhibit tolerance to antibiotics and are protected against the host responses, making it extremely difficult to treat and eradicate infectious biofilm [1,2]. Staphylococcus aureus is one of the main microorganisms involved in biofilm-related human infections and its ability to develop antimicrobial resistance adds even more complexity to the treatment of these infections [3]. In recognition of these challenges, many new anti-biofilm therapeutic strategies are being investigated. The strategies are focussed on the eradication of biofilm-embedded bacteria, which present different metabolic conditions than those in the planktonic state of growth. It has been suggested that colistin may be highly effective against dormant bacteria in anaerobic conditions, since colistin’s anti-biofilm activity is not dependent on the production of hydroxyl radicals [4]

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Conclusion