In Vivo Growth Rates Are Poorly Correlated with Phage Therapy Success in a Mouse Infection Model J. J. Bull a , c , d , G. Otto b and I. J. Molineux b , c a Section of Integrative Biology b Section of Molecular Genetics and Microbiology c Institute for Cellular and Molecular Biology d Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, USA ABSTRACT Two classes of phages yield profoundly different levels of recovery in mice experimentally infected with an Escherichia coli O18:K1:H7 strain. Phages requiring the K1 capsule for infection (K1-dep) rescue virtually all infected mice, whereas phages not requiring the capsule (K1-ind) rescue modest numbers (∼30%). To rescue infected mice, K1-ind phages require at least a 10 6 -fold-higher inoculum than K1-dep phages. Yet their in vivo growth dynamics are only modestly inferior to those of K1-dep phages, and competition between the two phage types in the same mouse reveals only a slight growth advantage for the K1-dep phage. The in vivo growth rate seems unlikely to be the primary determinant of phage therapy success. An alternative explanation is that the success of K1-dep phages is due substantially to their proteomic composition. They encode an enzyme that degrades the K1 capsule, which has been shown in other work to be sufficient to cure infection in the complete absence of phages.
In Vivo Growth Rates Are Poorly Correlated with Phage Therapy Success in a Mouse Infection Model
Abstract
In Vivo Growth Rates Are Poorly Correlated with Phage Therapy Success in a Mouse Infection Model J. J. Bull a , c , d , G. Otto b and I. J. Molineux b , c a Section of Integrative Biology b Section of Molecular Genetics and Microbiology c Institute for Cellular and Molecular Biology d Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, USA ABSTRACT Two classes of phages yield profoundly different levels of recovery in mice experimentally infected with an Escherichia coli O18:K1:H7 strain. Phages requiring the K1 capsule for infection (K1-dep) rescue virtually all infected mice, whereas phages not requiring the capsule (K1-ind) rescue modest numbers (∼30%). To rescue infected mice, K1-ind phages require at least a 10 6 -fold-higher inoculum than K1-dep phages. Yet their in vivo growth dynamics are only modestly inferior to those of K1-dep phages, and competition between the two phage types in the same mouse reveals only a slight growth advantage for the K1-dep phage. The in vivo growth rate seems unlikely to be the primary determinant of phage therapy success. An alternative explanation is that the success of K1-dep phages is due substantially to their proteomic composition. They encode an enzyme that degrades the K1 capsule, which has been shown in other work to be sufficient to cure infection in the complete absence of phages.Preview Only. This article cannot be rented because we do not currently have permission from the publisher.
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In Vivo Growth Rates Are Poorly Correlated with Phage Therapy Success in a Mouse Infection Model
Bull, J. J.; Otto, G.; Molineux, I. J.
Follow Antimicrobial Agents and Chemotherapy
, Volume 56 (2): 949
American Society For Microbiology – Feb 1, 2012
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