Characterization of the Lytic Capability of a LysK-Like Endolysin, Lys-phiSA012, Derived from a Polyvalent Staphylococcus aureus Bacteriophage

Fujiki, Jumpei; Nakamura, Tomohiro; Furusawa, Takaaki; Ohno, Hazuki; Takahashi, Hiroyuki; Kitana, Junya; Usui, Masaru; Higuchi, Hidetoshi; Tanji, Yasunori; Tsutsumi, Yutaka; Iwano, Hidetomo

doi:10.3390/ph11010025

Cited by 32 publications

(18 citation statements)

References 82 publications

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“…Likewise, an estimated 27% to 56% of nosocomial C. albicans bloodstream infections may be defined as polymicrobial [6]. Importantly, Staphylococcus aureus (S. aureus), which is recognized as one of the most significant disease-causing bacteria in humans, was found to be the third most commonly co-isolated species in conjunction with C. albicans [7,8]. Interestingly, the combined effect of C. albicans and S. aureus led to synergism and enhanced mortality in mice [9].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Sanguinarine Inhibits Mono- and Dual-Species Biofilm Formation by Candida albicans and Staphylococcus aureus and Induces Mature Hypha Transition of C. albicans

et al. 2020

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Previous studies have reported that sanguinarine possesses inhibitory activities against several microorganisms, but its effects on mono- and dual-species biofilms of C. albicans and S. aureus have not been fully elucidated. In this study, we aimed to evaluate the efficacy of sanguinarine for mono- and dual-species biofilms and explore its ability to induce the hypha-to-yeast transition of C. albicans. The results showed that the minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC90) of sanguinarine against C. albicans and S. aureus mono-species biofilms was 4, and 2 μg/mL, respectively, while the MIC and MBIC90 of sanguinarine against dual-species biofilms was 8, and 4 μg/mL, respectively. The decrease in the levels of matrix component and tolerance to antibiotics of sanguinarine-treated mono- and dual-species biofilms was revealed by confocal laser scanning microscopy combined with fluorescent dyes, and the gatifloxacin diffusion assay, respectively. Meanwhile, sanguinarine at 128 and 256 μg/mL could efficiently eradicate the preformed 24-h biofilms by mono- and dual-species, respectively. Moreover, sanguinarine at 8 μg/mL could result in the transition of C. albicans from the mature hypha form to the unicellular yeast form. Hence, this study provides useful information for the development of new agents to combat mono- and dual-species biofilm-associated infections, caused by C. albicans and S. aureus.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Sanguinarine Inhibits Mono- and Dual-Species Biofilm Formation by Candida albicans and Staphylococcus aureus and Induces Mature Hypha Transition of C. albicans

et al. 2020

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“…To extend this work and to understand the potential for PlyB as a broadly active therapeutic tool, we examined the lytic activity of PlyB against a wide range of B. cereus sensu lato strains using a spectrophotometry-based lytic assay that monitors the loss of optical density over a 20-min treatment period (indicated as the loss of milliOD 600 [milli-optical density at 600 nm] units per min [ϪmOD/min]). The lytic assay (and associated assays looking at bacterial clearing zones on agar plates) is commonly used to rapidly discern the bacteriolytic activity of endolysins against large target sets of bacterial strains (9,18,(30)(31)(32)(33)(34). Potent lytic activity was demonstrated for PlyB against every B. cereus sensu lato strain tested, including 44 B. cereus sensu stricto, 25 B. thuringiensis, 7 B. mycoides, and 3 B. anthracis strains ( Table 1 and Table S1).…”

Section: Resultsmentioning

confidence: 99%

The PlyB Endolysin of Bacteriophage vB_BanS_Bcp1 Exhibits Broad-Spectrum Bactericidal Activity against Bacillus cereus Sensu Lato Isolates

Schuch

Pelzek

Nelson

et al. 2019

Appl Environ Microbiol

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Lytic bacteriophages (or phages) drive bacterial mortality by elaborating exquisite abilities to bind, breach, and destroy bacterial cell membranes and subjugate critical bacterial cell functions. These antimicrobial activities make phages ideal candidates to serve as, or provide sources of, biological control measures for bacterial pathogens. In this study, we isolated the Myoviridae phage vB_BanS_Bcp1 (here referred to as Bcp1) from landfill soil, using a Bacillus anthracis host. The antimicrobial activities of both Bcp1 and its encoded endolysin, PlyB, were examined across different B. cereus sensu lato group species, including B. cereus sensu stricto, Bacillus thuringiensis, and Bacillus anthracis, with pathogenic potential in humans and multiple different uses in biotechnological applications. The Bcp1 phage infected only a subset (11 to 66%) of each B. cereus sensu lato species group tested. In contrast, functional analysis of purified PlyB revealed a potent bacteriolytic activity against all B. cereus sensu lato isolates tested (n ϭ 79). PlyB was, furthermore, active across broad temperature, pH, and salt ranges, refractory to the development of resistance, bactericidal as a single agent, and synergistic with a second endolysin, PlyG. To confirm the potential for PlyB as an antimicrobial agent, we demonstrated the efficacy of a single intravenous treatment with PlyB alone or combination with PlyG in a murine model of lethal B. anthracis infection. Overall, our findings show exciting potential for the Bcp1 bacteriophage and the PlyB endolysin as potential new additions to the antimicrobial armamentarium. IMPORTANCE Organisms of the Bacillus cereus sensu lato lineage are ubiquitous in the environment and are responsible for toxin-mediated infections ranging from severe food poisoning (B. cereus sensu stricto) to anthrax (Bacillus anthracis). The increasing incidence of many of these infections, combined with the specter of antibiotic resistance, has created a need for novel antimicrobials with potent activity, including bacteriophages (or phages) and phage-encoded products (i.e., endolysins). In this study, we describe a broadly infective phage, Bcp1, and its encoded endolysin, PlyB, which exhibited a rapidly bacteriolytic effect against all B. cereus sensu lato isolates tested with no evidence of evolving resistance. Importantly, PlyB was highly efficacious in a mouse model of lethal bacteremia with B. anthracis. Both the Bcp1 phage and the PlyB endolysin represent novel mechanisms of action compared to antibiotics, with potential applications to address the evolving problem of antimicrobial resistance.

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“…Turbidity reduction assay. The lytic activity of ⌽EF24C-P2 or VAN was assessed with a turbidity reduction assay performed as described previously (42). E. faecalis strains EF24, VRE2, GU01, GU02, and GU03 were grown in BHI broth at 37°C to an optical density at 600 nm (OD 600 ) of 0.8.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis

Kishimoto

Ishida

Fukuda

et al. 2019

Antimicrob Agents Chemother

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Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis. Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 104 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 107 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.

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Characterization of the Lytic Capability of a LysK-Like Endolysin, Lys-phiSA012, Derived from a Polyvalent Staphylococcus aureus Bacteriophage

Cited by 32 publications

References 82 publications

RETRACTED: Sanguinarine Inhibits Mono- and Dual-Species Biofilm Formation by Candida albicans and Staphylococcus aureus and Induces Mature Hypha Transition of C. albicans

RETRACTED: Sanguinarine Inhibits Mono- and Dual-Species Biofilm Formation by Candida albicans and Staphylococcus aureus and Induces Mature Hypha Transition of C. albicans

The PlyB Endolysin of Bacteriophage vB_BanS_Bcp1 Exhibits Broad-Spectrum Bactericidal Activity against Bacillus cereus Sensu Lato Isolates

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis

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