Researchers at The Rockefeller University have discovered a new method to selectively destroy pathogenic bacteria. The approach, which may prevent the bacteria evolving resistant strains as antibiotics do, is reported by the Proceedings of the National Academy of Sciences (PNAS) Online.
Bacteriophage lytic enzymes quickly destroy the cell wall of the host bacterium to release progeny phage. Because such lytic enzymes specifically kill the species in which they were produced, they may represent an effective way to control pathogenic bacteria without disturbing normal microflora. In this report, the authors studied a murein hydrolase from the streptococcal bacteriophage C1 termed lysin. This enzyme is specific for groups A, C and E streptococci, with little or no activity toward several oral streptococci or other commensal organisms tested. Using purified lysin in vitro, 1,000 units (10 ng) of enzyme is sufficient to sterilise a culture of approximately 107 group A streptococci within 5 seconds. When a single dose of lysin (250 units) is introduced into the oral cavity of mice, followed by 107 live group A streptococci, protection against colonisation is conferred. . Furthermore, when lysin (500 units) was given orally to heavily colonised mice, no detectable streptococci were observed 2 h after lysin treatment. In all, these studies show that lysin represents a unique murein hydrolase that has a rapid lethal effect, both in vitro and in vivo, on group A streptococci, without affecting other indigenous microorganisms analysed. This general approach may be used to either eliminate or reduce streptococci from the upper respiratory mucosal epithelium of carriers and infected individuals, thus reducing associated disease.
The US military has become interested in this work because of a need to control streptococcal infections among its recruits. Antibiotic resistance has compelled the military to look for alternative treatments and hope is now focused on the phage enzyme. The same approach could be used to protect children in day-care centres and schools.
Bacteriophages were discovered in 1917 by Twort and d’Herelle and were initially thought to be of use as antibacterial agents. However, phages must bind to specific bacterial cell wall receptors before being able to inject their DNA; as bacteria evolve, they change their receptors and shut out the phages. Because scientists would constantly have to develop new phages to keep up with this rapid change, phage therapy never took off as a technology.
The senior author of the article, Vincent A. Fischetti characterises his findings as a "platform technology" in which phage enzymes from a wide range of disease bacteria may be used to control these organisms. The method has obvious applications also in the veterinary scene.
In January 2000 PNAS Online sarted a new feature called PNAS "Early Edition". In this section of their web site, articles are published online 1 to 5 weeks before they appear in print. For the momemt the release of articles is weekly, but the journal aims eventually to increase this to a daily publication update. The date of online release is posted on the web site and is the official date of publication. PNAS offers electronic publication in as little as 5 weeks after acceptance to authors who return their proofs quickly.
The rapid publication of papers, without the restrictions and associated delays of publishing in conventional paper 'issues', will have obvious benefits for both authors and readers.
Publication date of this paper on PNAS Online was 20 March 2001.