Abstract
Staphylococcus epidermidis is a major causative agent of nosocomial infections, mainly associated with the use of indwelling devices, on which this bacterium forms structures known as biofilms. Due to biofilms’ high tolerance to antibiotics, virulent bacteriophages were previously tested as novel therapeutic agents. However, several staphylococcal bacteriophages were shown to be inefficient against biofilms. In this study, the previously characterized S. epidermidis-specific Sepunavirus phiIBB-SEP1 (SEP1), which has a broad spectrum and high activity against planktonic cells, was evaluated concerning its efficacy against S. epidermidis biofilms. The in vitro biofilm killing assays demonstrated a reduced activity of the phage. To understand the underlying factors impairing SEP1 inefficacy against biofilms, this phage was tested against distinct planktonic and biofilm-derived bacterial populations. Interestingly, SEP1 was able to lyse planktonic cells in different physiological states, suggesting that the inefficacy for biofilm control resulted from the biofilm 3D structure and the protective effect of the matrix. To assess the impact of the biofilm architecture on phage predation, SEP1 was tested in disrupted biofilms resulting in a 2 orders-of-magnitude reduction in the number of viable cells after 6 h of infection. The interaction between SEP1 and the biofilm matrix was further assessed by the addition of matrix to phage particles. Results showed that the matrix did not inactivate phages nor affected phage adsorption. Moreover, confocal laser scanning microscopy data demonstrated that phage infected cells were less predominant in the biofilm regions where the matrix was more abundant. Our results provide compelling evidence indicating that the biofilm matrix can work as a barrier, allowing the bacteria to be hindered from phage infection.
Highlights
Medical device-related infections are among the most common healthcare-associated infections (HAIs), causing increased morbidity and mortality on patients, which poses an abundant economic burden on healthcare services [1,2]
Biofilms are composed of persister cells, which are a subset of antibiotic-tolerant cells within a bacterial population [9]
The results demonstrated that the biofilm matrix did not impair phage’s infectivity, as no significant differences (p > 0.05) were detected in the phage titer between matrix containing experiments and the negative control (Figure 4a)
Summary
Medical device-related infections are among the most common healthcare-associated infections (HAIs), causing increased morbidity and mortality on patients, which poses an abundant economic burden on healthcare services [1,2]. It is estimated that about 60–70% of HAIs are biofilm-related infections associated with implanted medical devices [4]. Biofilms are composed of persister cells, which are a subset of antibiotic-tolerant cells within a bacterial population [9]. These cells are more prevalent in biofilms than on log-phase planktonic cultures, being associated with the recalcitrance of many chronic infections [10,11]. Another important reason for biofilm therapy inefficacy is related to the release of bacterial cells from the biofilm. It was initially thought that BRCs quickly revert to the planktonic phenotype [15], there is evidence that these cells are distinct from planktonic cells, showing higher virulence potential [16]
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