2004
DOI: 10.1128/aac.48.5.1503-1508.2004
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Prevention and Cure of Systemic Escherichia coli K1 Infection by Modification of the Bacterial Phenotype

Abstract: Escherichia coli is a common cause of meningitis and sepsis in the newborn infant, and the large majority of isolates from these infections produce a polysialic acid (PSA) capsular polysaccharide, the K1 antigen, that protects the bacterial cell from immune attack. We determined whether a capsule-depolymerizing enzyme, by removing this protective barrier, could alter the outcome of systemic infection in an animal model. Bacteriophage-derived endosialidase E (endoE) selectively degrades the PSA capsule on the s… Show more

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Cited by 98 publications
(129 citation statements)
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“…With a litter of 12 pups as a single test cohort, power calculations using G* Power Software determined that this sample size equates to a 98.6% probability of finding an effect based on survival using six animals from the cohort and >99% probability if all twelve are taken into consideration. The model is therefore suitable for evaluation of novel agents specifically tailored for the treatment of neonatal bacterial infections and has been used in the procedure to evaluate the therapeutic potential of the capsule depolymerase EndoE that selectively removes the K1 capsule from the bacterial surface [24][25][26] . It may also be used to investigate hostbacteria interactions that impact on the pathogenesis of E. coli neuropathogens; within this context it has been employed for studies of E. coli A192PP colonization and dissemination.…”
Section: Representative Resultsmentioning
confidence: 99%
“…With a litter of 12 pups as a single test cohort, power calculations using G* Power Software determined that this sample size equates to a 98.6% probability of finding an effect based on survival using six animals from the cohort and >99% probability if all twelve are taken into consideration. The model is therefore suitable for evaluation of novel agents specifically tailored for the treatment of neonatal bacterial infections and has been used in the procedure to evaluate the therapeutic potential of the capsule depolymerase EndoE that selectively removes the K1 capsule from the bacterial surface [24][25][26] . It may also be used to investigate hostbacteria interactions that impact on the pathogenesis of E. coli neuropathogens; within this context it has been employed for studies of E. coli A192PP colonization and dissemination.…”
Section: Representative Resultsmentioning
confidence: 99%
“…We postulate that tumors co-opt the immune system's strategy of using polySia to modulate responses to chemokines and growth factors, thus gaining a competitive advantage. Regarding bacteria, polySia expression is correlated with the virulence of pathogenic strains of Escherichia coli K1 and group B Neisseria meningitidis (38,39). It is possible that bacterial polySia binds and neutralizes AMPs, sequestering them at a safe distance from the cell wall.…”
Section: Discussionmentioning
confidence: 99%
“…Avery and Dubos extended these ideas to demonstrate that microbial enzymes could be used to remove the capsule from the pneumococcus and successfully treat experimental infections (2). Similar approaches have been used in experimental Escherichia coli infections (37,38).…”
mentioning
confidence: 98%