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Journal of Virology, June 2002, p. 5557-5564, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5557-5564.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Overcoming the Phage Replication Threshold: a Mathematical Model with Implications for Phage Therapy

Laura M. Kasman,1* Alex Kasman,2 Caroline Westwater,1 Joseph Dolan,1 Michael G. Schmidt,1 and James S. Norris1

Department of Microbiology and Immunology, Medical University of South Carolina,1 Department of Mathematics, College of Charleston, Charleston, South Carolina2

Received 2 November 2001/ Accepted 17 February 2002

Prior observations of phage-host systems in vitro have led to the conclusion that susceptible host cell populations must reach a critical density before phage replication can occur. Such a replication threshold density would have broad implications for the therapeutic use of phage. In this report, we demonstrate experimentally that no such replication threshold exists and explain the previous data used to support the existence of the threshold in terms of a classical model of the kinetics of colloidal particle interactions in solution. This result leads us to conclude that the frequently used measure of multiplicity of infection (MOI), computed as the ratio of the number of phage to the number of cells, is generally inappropriate for situations in which cell concentrations are less than 107/ml. In its place, we propose an alternative measure, MOIactual, that takes into account the cell concentration and adsorption time. Properties of this function are elucidated that explain the demonstrated usefulness of MOI at high cell densities, as well as some unexpected consequences at low concentrations. In addition, the concept of MOIactual allows us to write simple formulas for computing practical quantities, such as the number of phage sufficient to infect 99.99% of host cells at arbitrary concentrations.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Medical University of South Carolina, BSB-Rm. 201, P.O. Box 250504, 173 Ashley Ave., Charleston, SC 29403. Phone: (843) 792-2074. Fax: (843) 792-2464. E-mail: KASMANL{at}musc.edu.

Journal of Virology, June 2002, p. 5557-5564, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5557-5564.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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