Molecular analysis of the contribution of the capsular polysaccharide and the lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a murine model of pneumonia.
Klebsiella pneumoniae is a common cause of gram-negative bacterial nosocomial pneumonia. Two surface polysaccharides, lipopolysaccharide (LPS) O side chain and capsular polysaccharide (CPS), are critical for the microorganism in causing sepsis, but little is known about their role in pneumonia. To investigate their contribution in the pathogenesis of K. pneumoniae pneumonia, we characterized the host response to bacterial challenge with a highly virulent clinical isolate or with isogenic insertion-duplication mutants deficient in CPS or LPS O side chain in a murine model of pneumonia. Animals challenged intratracheally with the wild-type or LPS O side chain-deficient strain developed pneumonia and became bacteremic before death. Extensive lung lesions as well as pleuritis, vasculitis, and edema were observed by histopathological examination, and polymorphonuclear infiltration was also demonstrated. In contrast, none of the animals challenged with the unencapsulated strain developed pneumonia or bacteremia. Examination of tissue from this group did not identify lung lesions, and none of the infected animals died. Analysis of the early host defense mechanisms that contributed to the clearance of the unencapsulated mutant showed that the levels of C3 deposited on the unencapsulated mutant surface were threefold higher than those for the wild-type and LPS O side chain-deficient strains. Furthermore, phagocytosis of the unencapsulated mutant by human alveolar macrophages (AM) was more efficient than that of the wild-type and LPS O side chain-deficient strains. We conclude that CPS, but not LPS O side chain, is essential for Klebsiella pneumonia because it modulates the deposition of C3 and protects the microorganisms against human AM phagocytosis.
Cortés
Guadalupe
G
Unidad de Investigación, Hospital Universitario Son Dureta, Palma de Mallorca, Spain.
Borrell
Nuria
N
de Astorza
Beatriz
B
Gómez
Cristina
C
Sauleda
Jaume
J
Albertí
Sebastián
S
D016667:Bacterial Capsules / Q000633:toxicity*; D004195:Disease Models, Animal; D006801:Humans; D007711:Klebsiella pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D016676:Macrophages, Alveolar / Q000276:immunology; D019081:O Antigens / Q000633:toxicity*; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000209:etiology*; D014774:Virulence
D019081:O Antigens