Thursday, 04 May 2017 09:41

Bacteriophage Lysin Shows Promising Antibiofilm Activity

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Published in mBiosphere

Bacteriophage, viruses that specifically attack a bacterial species or strain, have been proposed (and in some cases, tested) to address many microbial issues: from treating recalcitrant infections to eliminating wastewater contaminants. A new Antimicrobial Agents and Chemotherapy report describes the successful application of a bacteriophage product against one of modern medicine’s most deadly foes: methicillin-resistant Staphylococcus aureus (MRSA) biofilms. 

AACJournal: Bacteriophage Lysin CF-301: A Potent Anti-Staphylococcal Biofilm Agent

The group, led by senior scientist Michael Wittekind, wanted to test a bacteriophage-derived lysin called CF-301 (also called PlySs2). Endolysins are phage-produced peptidoglycan hydrolases that degrade the bacterial cell wall to facilitate the escape of progeny phage an infected bacterial cell; the CF-301 lysin is a product from a Streptococcus suis bacteriophage, which though found in a streptococcal isolate, is also active against staphylococcal species. This broad antibacterial activity is rare among phage lysins, making CF-301 a promising therapeutic agent. Previous research had shown that combining CF-301 with antibiotics increases antibacterial infection in bacteremia, but no experiments had addressed the antibiofilm properties of CF-301.

Biofilms are a huge medical problem, especially in a hospital setting. Their extracellular matrix makes biofilms innately more drug resistant than a planktonic culture of the same species and thus very difficult to eradicate. Additionally, microbes can exit the biofilm and initiate infection elsewhere, which can include resuming a planktonic lifestyle. Many healthcare-associated procedures require catheters, intravenous lines, and other indwelling devices that provide ideal surfaces for microbes to form biofilms, and an anti-biofilm agent would be a valuable therapeutic asset. 

Screen Shot 2017 05 03 at 12.57.40 PMSEM images of S. aureus biofilms on catheters after treatment with CF-301 or buffer alone. source

The research team tested CF-301 against S. aureus biofilms on polystyrene, glass, surgical mesh, and catheters. The compound was most effective against biofilms in catheters, eliminating all biofilm-associated bacteria within an hour (see figure, right). Lysins also have bacterial-killing activity, which resulted in all bacterial cells being lysed within six hours of treatment. CF-301 disrupted all single-species staphylococcal and streptococcal biofilms, as well as mixed-species biofilms composed of S. aureus and S. epidermidis. Since many biofilms are composed of a number of different species (and even different kingdoms), efficacy against these mixed-species biofilms is important.

Sometimes two drugs are more effective than one. Previous studies showed CF-301 can lower the antibiotic concentration needed to kill MRSA during bacteremia, and this study demonstrated the synergy of CF-301 with another lysin-like molecule, lysostaphin, in eliminating biofilms. Multiple drugs can both lower the effective concentration and decrease possible development of resistance, though the authors noted they observed “no resistance to CF-301 was ever observed following treatment with CF-301.” 

The compound was found to be active in the presence of plasma, serum, blood, and synovial fluid, supporting the use of CF-301 in the complex host environment. The next step is for the researchers to look at the ability of CF-301 to eliminate biofilms during an in vivo infection. This will be important to assess possible therapeutic use of CF-301 against endocarditis or septic arthritis infections, broadening the use of the already-developing application of CF-301 against bacteremia.

Last modified on Thursday, 04 May 2017 09:59
Julie Wolf

ASM Communications Social Media Specialist Julie Wolf spent her research career focused on medical mycology and infectious disease. Broadly interested in microbiology and scientific communication, she has taught at Long Island University and the community biolab Genspace and has written for the Scientista Foundation and Scholastic’s Science World magazine. Follow her on Twitter for more ASM and Microbiology highlights at @JulieMarieWolf.