DOI: 10.1128/iai.71.11.6199-6204.2003. Phage Lytic Enzyme Cpl-1 as a Novel Antimicrobial for Pneumococcal Bacteremia

Phage Lytic Enzyme Cpl-1 as a Novel Antimicrobial for Pneumococcal Bacteremia

10.1128/iai.71.11.6199-6204.2003

Crossref journal-article

American Society for Microbiology

Infection and Immunity (235)

Abstract

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 (<log 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.

Bibliography

Loeffler, J. M., Djurkovic, S., & Fischetti, V. A. (2003). Phage Lytic Enzyme Cpl-1 as a Novel Antimicrobial for Pneumococcal Bacteremia. Infection and Immunity, 71(11), 6199â6204.

Authors 3

Jutta M. Loeffler (first)
Svetolik Djurkovic (additional)
Vincent A. Fischetti (additional)

References 20 Referenced 216

10.1097/00006454-200003000-00003
10.1097/00006454-200209000-00005
10.1182/blood.V76.1.73.73
10.1086/339525
10.1128/CMR.15.2.155-166.2002
10.1097/00006454-200301000-00006
10.1128/jvi.61.8.2573-2580.1987
10.1136/adc.88.3.211
10.1128/AAC.47.1.375-377.2003
10.1126/science.1066869
McCormick, A. W., C. G. Whitney, M. M. Farley, R. Lynfield, L. H. Harrison, N. M. Bennett, W. Schaffner, A. Reingold, J. Hadler, P. Cieslak, M. H. Samore, and M. Lipsitch. 2003. Geographic diversity and temporal trends of antimicrobial resistance in Streptococcus pneumoniae in the United States. Nat. Med.10:10. / Nat. Med. (2003)
10.1073/pnas.061038398
10.1046/j.1365-2796.2002.01049.x
10.1016/S0022-3476(97)70356-1
10.1111/j.1432-1033.1990.tb15319.x
10.1038/nature01026
10.1046/j.1365-2958.1997.5101880.x
10.1053/euhj.1999.1528
10.1056/NEJMoa022823
10.1006/mpat.1997.0142

Dates

Type	When
Created	21 years, 10 months ago (Oct. 23, 2003, 10:31 p.m.)
Deposited	3 years, 5 months ago (March 4, 2022, 10:19 p.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 7:24 a.m.)
Issued	21 years, 9 months ago (Nov. 1, 2003)
Published	21 years, 9 months ago (Nov. 1, 2003)
Published Print	21 years, 9 months ago (Nov. 1, 2003)

Funders 0

None

BibTeX

@article{Loeffler_2003, title={Phage Lytic Enzyme Cpl-1 as a Novel Antimicrobial for Pneumococcal Bacteremia}, volume={71}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.71.11.6199-6204.2003}, DOI={10.1128/iai.71.11.6199-6204.2003}, number={11}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Loeffler, Jutta M. and Djurkovic, Svetolik and Fischetti, Vincent A.}, year={2003}, month=nov, pages={6199–6204} }

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