NEW YORK (Reuters Health) - A genetically modified, nonreplicating phage is effective against Pseudomonas aeruginosa infections in mice, Austrian researchers report in the October issue of Antimicrobial Agents and Chemotherapy.
“Alternative strategies towards new antimicrobial agents are feasible,” Dr. Udo Blaesi from Max F. Perutz Laboratories, Vienna, told Reuters Health. “Such new agents could be specifically used to combat a particular pathogen.”
Dr. Blaesi and colleagues studied the effectiveness of Pf3R, a nonlytic, nonreplicating phage bearing a toxin gene, against experimental P. aeruginosa infection.
Pseudomonas cultures treated with Pf3R showed greater than 99% declines in colony-forming units after 90 minutes, the authors report, but the nonviable bacteria remained structurally intact.
Endotoxin levels in supernatant from these cultures increased no more than 5-fold at 90 minutes and 7-fold at 4 hours. In contrast, endotoxin levels increased 32-fold and 60-fold, respectively, after Pseudomonas infection by the lytic phage Pt1.
Treatment of mice with Pf3R 45 minutes after infection with three times the lethal dose of Pseudomonas reduced the mortality from 100% to less than 25%, the researchers note. Treatment 6 hours after infection reduced mortality to zero.
Results were similar after infection with five times the lethal dose of Pseudomonas. Mortality was consistently higher after treatment with the Pt1 lytic phage.
Thus the researchers observe that “the use of nonreplicative phage in phage therapy of an experimental bacterial infection can be as effective as the use of replicating phage.”
Nevertheless Dr. Blaesi concluded that more extensive studies are needed to establish that they “are as effective and really cause a reduced inflammatory response.”
Source: Antimicrob Agents Chemother 2004;48:3817-3822. [ Google search on this article ]
MeSH Headings:Genetic Engineering: Genetic Techniques: Investigative Techniques: Pseudomonas Infections: Gram-Negative Bacterial Infections: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
