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Haemophilus influenzae localized in epithelial cell layers is shielded from antibiotics and antibody-mediated bactericidal activity.

Abstract：

:Nonencapsulated Haemophilus influenzae frequently persists in the lungs of chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) patients for prolonged periods of time. The bacteria are not eradicated by antibiotic treatment of the patients or by specific antibodies that are found in the sputum and sera of these patients. We investigated whether H. influenzae, when localized in lung epithelial cell layers, is shielded from antibiotics and from antibody-mediated bactericidal activity of specific antibodies. An in vitro model system consisting of lung epithelial NCI-H292 cells on permeable supports was developed to allow long term association of H. influenzae with the cells. Microscopic examination showed increasing numbers of H. influenzae bacteria between the epithelial cells up to 24 h of incubation. Coinciding with the microscopic observations the maximum number of cell-associated bacteria surviving gentamicin treatment of the cell layers was obtained after 24 h of incubation. All H. influenzae strains, and one Haemophilus parainfluenzae strain tested penetrated into the cell layer as determined by gentamicin killing. Cell-associated bacteria were shielded from the bactericidal activity of several antibiotics and from antibody-mediated bactericidal activity. After prolonged incubation in the cell system in the presence of a specific bactericidal antibody against major outer membrane protein (MOMP) P2, antigenic variation occurred due to a point mutation in the MOMP P2 gene, similar to point mutations observed in vivo. We conclude that penetration of H. influenzae between lung epithelial cells results in shielding the bacteria from killing by antibody dependent defense mechanisms and by antibiotics. Therefore, penetration of H. influenzae between epithelial cells may contribute to the persistence of this microorganism in COPD and CF patients.

journal_name

Microb Pathog

journal_title

Microbial pathogenesis

authors

van Schilfgaarde M,Eijk P,Regelink A,van Ulsen P,Everts V,Dankert J,van Alphen L

doi

10.1006/mpat.1998.0269

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

249-62

issue

5

eissn

0882-4010

issn

1096-1208

pii

S0882-4010(98)90269-8

journal_volume

26

pub_type

杂志文章

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