Using Bacteriophage Enzymes to Stay One Step Ahead of MRSA

By: Davidta Brown, Copy Editor [Content-Focused]

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It’s difficult to have a discussion about antibiotics without mentioning the developing crisis of antibiotic-resistance. Pathogens like MRSA (methicillin-resistant Staphylococcus aureus) have become a part of the general public’s consciousness – a household name and a community-acquired “superbug.” With the last new class of antibiotics developed in the 1980s, bacterial strains are rapidly out-mutating our ability to contain them.¹ Thankfully, hope in this microscopic arms race is appearing in the form of a new method of bacterial destruction, indicating that perhaps an alternative to antibiotics is only a few years in the making.

Bacteriophages, viruses that infect bacteria, release lytic enzymes called endolysins that perforate the bacterial cell wall on their way out of an infected cell and toward a new bacterial host cell.² In the past few years, researchers have been manipulating this technique in the hopes of creating lytic substances that can be administered from the outside, rather than the inside, of pathogenic bacterial cells. One experiment evaluated the efficacy of bacteriophage endolysin SAL-1 as therapy against S. aureus infections. The stability of the endolysin was improved by incorporation of calcium ions and Poloxamer 188, creating a compound referred to as SAL200.³ Impressively, SAL200 showed quick and effective antibacterial activity against S. aureus, and what’s more, 336 MRSA isolates and 1 VISA (Vancomycin-intermediate S. aureus) isolate were susceptible to the compound.³

Another study tried to improve the solubility of bactericidal endolysins by combining the desired lytic active site of one strain of endolysin with the soluble portions of endolysins from another species.² The recombinant endolysins contained staphylolytic activity as well as the solubility of the enterococcal endolysins from which they were partially derived. As a result, they offer an answer to the difficulty of large-scale production, a process that would otherwise be hindered by poor solubility.²

Scientists around the world are pursuing this new avenue of antibacterial processes. If such progress continues, compounds like the LysK enzyme or PlyGRCS may soon be on their way to clinical trials.^4,5 Without a doubt, the need to develop creative antibiotic alternatives to battle resistant species is becoming more and more pressing. Experimentation with endolysins suggests that bacteriophage viruses may already be employing the innovative methods that are so desperately needed.

SOURCES:

1. Perry K. Scientists develop antibiotic-free drug for MRSA. The Telegraph. Available at: http://www.telegraph.co.uk/science/11212480/Scientists-develop-antibiotic-free-drug-for-MRSA.html. Published 2014. Accessed November 24, 2014.
2. Fernandes S, Proença D, Cantante C, et al. Novel chimerical endolysins with broad antimicrobial activity against methicillin-resistant Staphylococcus aureus. Microb Drug Resist. 2012;18(3):333-343.
3. Jun S, Jung G, Yoon S, et al. Antibacterial properties of a pre-formulated recombinant phage endolysin, SAL-1. Int J of Antimicrob Agents. 2013;41(2):156-161.
4. Filatova L, Donovan D, Becker S, et al. Physicochemical characterization of the staphylolytic LysK enzyme in complexes with polycationic polymers as a potent antimicrobial. Biochimie. 2013;95(9):1689-96. 5.
5. Linden S, Zhang H, Heselpoth R, et al. Biochemical and biophysical characterization of PlyGRCS, a bacteriophage endolysin active against methicillin-resistant Staphylococcus aureus. Appl Microbiol and Biotechnol. 2014.

[pubmed_related keyword1=”bacteriophage” keyword2=”enzyme” keyword3=”MRSA”]