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The Klebsiella pneumoniae O Antigen Contributes to Bacteremia and Lethality during Murine Pneumonia

Sunita Shankar-Sinha,^1, Gabriel A. Valencia,^1, Brian K. Janes,² Jessica K. Rosenberg,¹ Chris Whitfield,³ Robert A. Bender,² Ted J. Standiford,⁴ and John G. Younger^1*

Departments of Emergency Medicine,¹ Internal Medicine, School of Medicine,⁴ Department of Molecular, Cellular, and Developmental Biology, School of Literature, Science, and Arts, University of Michigan, Ann Arbor, Michigan,² Department of Microbiology, University of Guelph, Guelph, Ontario, Canada³

Received 8 May 2003/ Returned for modification 16 July 2003/ Accepted 21 November 2003

Bacterial surface carbohydrates are important pathogenic factors in gram-negative pneumonia infections. Among these factors, O antigen has been reported to protect pathogens against complement-mediated killing. To examine further the role of O antigen, we insertionally inactivated the gene encoding a galactosyltransferase necessary for serotype O1 O-antigen synthesis (wbbO) from Klebsiella pneumoniae 43816. Analysis of the mutant lipopolysaccharide by sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the absence of O antigen. In vitro, there were no detectable differences between wild-type K. pneumoniae and the O-antigen-deficient mutant in regard to avid binding by murine complement C3 or resistance to serum- or whole-blood-mediated killing. Nevertheless, the 72-h 50% lethal dose of the wild-type strain was 30-fold greater than that of the mutant (2 x 10³ versus 6 x 10⁴ CFU) after intratracheal injection in ICR strain mice. Despite being less lethal, the mutant organism exhibited comparable intrapulmonary proliferation at 24 h compared to the level of the wild type. Whole-lung chemokine expression (CCL3 and CXCL2) and bronchoalveolar inflammatory cell content were also similar between the two infections. However, whereas the wild-type organism produced bacteremia within 24 h of infection in every instance, bacteremia was not seen in mutant-infected mice. These results suggest that during murine pneumonia caused by K. pneumoniae, O antigen contributes to lethality by increasing the propensity for bacteremia and not by significantly changing the early course of intrapulmonary infection.

Editor: J. N. Weiser

S.S.-S. and G.A.V. contributed equally as first authors to this work.

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