Phage Lytic Enzyme Cpl-1 as a Novel Antimicrobial for Pneumococcal Bacteremia
- 1 November 2003
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 71 (11), 6199-204
- https://doi.org/10.1128/iai.71.11.6199-6204.2003
Abstract
Streptococcus pneumoniae is becoming increasingly antibiotic resistant worldwide, and thus new antimicrobials are badly needed. We report the use of Cpl-1, the lytic enzyme of a pneumococcal bacteriophage, as an intravenous therapy for pneumococcal bacteremia in a mouse model. A 2,000-μg dose of Cpl-1 reduced pneumococcal titers from a median of log 10 4.70 CFU/ml to undetectable levels (10 2.00 CFU/ml) within 15 min. This dose given 1 h after intravenous infection led to 100% survival at 48 h, compared to the 20% survival of buffer-treated controls. In advanced bacteremia, treatment with two doses at 5 and 10 h still resulted in significantly longer survival ( P < 0.0001) and a hazard ratio of 0.29 (95% confidence interval, 0.04 to 0.35). The enzyme is immunogenic, but the treatment efficacy was not significantly diminished after previous intravenous exposure of mice and hyperimmune rabbit serum did not neutralize the activity. Cpl-1 is also very effective as a topical nasal treatment against colonization by S. pneumoniae . In vitro, the enzyme is active against many serotypes of S. pneumoniae , independent of their penicillin resistance, and it is very specific for this species. Bacteriophage enzymes are unusual but extremely effective antimicrobials and represent a new weapon against infections with resistant bacteria.Keywords
This publication has 20 references indexed in Scilit:
- Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancyArchives of Disease in Childhood, 2003
- Synergistic Lethal Effect of a Combination of Phage Lytic Enzymes with Different Activities on Penicillin-Sensitive and -Resistant Streptococcus pneumoniae StrainsAntimicrobial Agents and Chemotherapy, 2003
- Impact of the pneumococcal conjugate vaccine on otitis mediaThe Pediatric Infectious Disease Journal, 2003
- The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarctionJournal of Internal Medicine, 2002
- Reduction of Nasopharyngeal Carriage ofStreptococcus pneumoniaeafter Administration of a 9‐Valent Pneumococcal Conjugate Vaccine to Toddlers Attending Day Care CentersThe Journal of Infectious Diseases, 2002
- Rapid Killing of Streptococcus pneumoniae with a Bacteriophage Cell Wall HydrolaseScience, 2001
- Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in childrenThe Pediatric Infectious Disease Journal, 2000
- Humoral and cellular immune responses up to 7·5 years after administration of streptokinase for acute myocardial infarctionPublished by Oxford University Press (OUP) ,1999
- Repeated invasive pneumococcal infections in young children without apparent underlying immunodeficiencyThe Journal of Pediatrics, 1997
- Structural studies of the lysozyme coded by the pneumococcal phage Cp‐1European Journal of Biochemistry, 1990