Application of a Bacteriophage Lysin To Disrupt Biofilms Formed by the Animal Pathogen Streptococcus suis

Meng, Xiangpeng; Shi, Yiting; Ji, Wenhui; Meng, Xueling; Zhang, Jing; Wang, Hengan; Chen, Lu; Sun, Jianhe; Yan, Yaxian

doi:10.1128/aem.05151-11

Cited by 93 publications

(70 citation statements)

References 33 publications

(48 reference statements)

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“…Bacterial strains were stored at Ϫ80°C. The strains used in this study include S. aureus ATCC BAA- 42 Tables S2 and S3. The BAA-42 strain was chosen as a model strain in this study based on its strong propensity to form biofilms (43); it is a pediatric MRSA clone isolated in 1996 from a pneumology ward in Lisbon, Portugal (67).…”

Section: Methodsmentioning

confidence: 99%

Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent

Schuch

Khan

Raz

et al. 2017

Antimicrob Agents Chemother

127

100

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Biofilms pose a unique therapeutic challenge because of the antibiotic tolerance of constituent bacteria. Treatments for biofilm-based infections represent a major unmet medical need, requiring novel agents to eradicate mature biofilms. Our objective was to evaluate bacteriophage lysin CF-301 as a new agent to target Staphylococcus aureus biofilms. We used minimum biofilm-eradicating concentration (MBEC) assays on 95 S. aureus strains to obtain a 90% MBEC (MBEC 90 ) value of Յ0.25 g/ml for CF-301. Mature biofilms of coagulase-negative staphylococci, Streptococcus pyogenes, and Streptococcus agalactiae were also sensitive to disruption, with MBEC 90 values ranging from 0.25 to 8 g/ml. The potency of CF-301 was demonstrated against S. aureus biofilms formed on polystyrene, glass, surgical mesh, and catheters. In catheters, CF-301 removed all biofilm within 1 h and killed all released bacteria by 6 h. Mixed-species biofilms, formed by S. aureus and Staphylococcus epidermidis on several surfaces, were removed by CF-301, as were S. aureus biofilms either enriched for small-colony variants (SCVs) or grown in human synovial fluid. The antibacterial activity of CF-301 was further demonstrated against S. aureus persister cells in exponential-phase and stationary-phase populations. Finally, the antibiofilm activity of CF-301 was greatly improved in combinations with the cell wall hydrolase lysostaphin when tested against a range of S. aureus strains. In all, the data show that CF-301 is highly effective at disrupting biofilms and killing biofilm bacteria, and, as such, it may be an efficient new agent for treating staphylococcal infections with a biofilm component.KEYWORDS biofilm, CF-301, lysin, Staphylococcus aureus O ver 99.9% of bacteria in the biosphere grow within robust and resilient sessile communities called biofilms (1). Biofilm formation is a precisely controlled developmental process initiated by microbial aggregation on abiotic and biotic surfaces. Importantly, biofilms form in human tissues, facilitating serious chronic infections of the upper respiratory tract, intestinal tract, urinary tract, bone, heart valves, middle ear, gingiva, and skin that can lead to serious illness and death (2, 3). Indwelling medical devices, such as intravenous catheters, stents, prosthetic joints, and pacemakers, are frequent sites of biofilm formation and are increasingly associated with morbidity and mortality. In clinical medicine, 65 to 80% of bacterial infections are biofilm associated, costing the health care system billions of dollars each year (4-6).Biofilms are densely packed microbial populations held within DNA, polysaccharide, and/or proteinaceous matrices (7). In the context of human disease, the biofilm matrix helps protect bacteria from innate and adaptive immune defenses and enables up to 1,000-fold increases in antibiotic tolerance compared to tolerance with planktonic bacteria. Biofilm microenvironments favor horizontal transfer of antibiotic resistance genes (8) and drive the inactivation of antibiot...

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Section: Methodsmentioning

confidence: 99%

Bacteriophage Lysin CF-301, a Potent Antistaphylococcal Biofilm Agent

Schuch

Khan

Raz

et al. 2017

Antimicrob Agents Chemother

127

100

View full text Add to dashboard Cite

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“…In the last decade, natural and engineered lysins have been demonstrated extensively to be therapeutic agents with activity against various Gram-positive pathogens both in vitro and in vivo (15)(16)(17). Some investigations have also shown the activities of several lysins against staphylococcal biofilms (16,18) and streptococcal biofilms (19)(20)(21), indicating the advantages of lysins over traditional antibiotics in removing biofilms. However, no studies to date have reported on lysins effective against S. mutans biofilms.…”

mentioning

confidence: 99%

Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions

Yang

Shang

et al. 2016

Antimicrob Agents Chemother

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dStreptococcus mutans often survives as a biofilm on the tooth surface and contributes to the development of dental caries. We investigated the efficacy of ClyR, an engineered chimeolysin, against S. mutans biofilms under physiological and cariogenic conditions. Susceptibility tests showed that ClyR was active against all clinical S. mutans isolates tested as well as S. mutans biofilms that displayed resistance to penicillin. The S. mutans biofilms that formed on hydroxyapatite discs under physiological sugar conditions and cariogenic conditions were reduced ϳ2 logs and 3 logs after treatment with 100 g/ml ClyR, respectively. In comparison, only a 1-log reduction was observed in the chlorhexidine gluconate (ChX)-treated group, and no killing effect was observed in the NaF-treated group. A mouse dental colonization model showed that repeated use of ClyR for 3 weeks (5 g/day) reduced the number of colonized S. mutans cells in the dental plaques significantly (P < 0.05) and had no harmful effects on the mice. Furthermore, toxicity was not noted at concentrations exceeding those used for the in vitro and in vivo studies, and ClyRspecific antibodies could not be detected in mouse saliva after repeated use of ClyR in the oral cavity. Our data collectively demonstrate that ClyR is active against S. mutans biofilms both in vitro and in vivo, thus representing a preventative or therapeutic agent for use against dental caries.

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“…It was shown to increase dispersal of Streptococcus suis strains SS2-4 and SS2-H in conjunction with antibiotic treatment; the combination of LySMP and antibiotic treatment resulted in synergistic killing of S. suis (Meng et al 2011 ).…”

Section: Bacteriophagesmentioning

confidence: 96%