Regions important for the adhesin activity of Moraxella catarrhalis Hag

被引:25
作者
Bullard, Brian
Lipski, Serena
Lafontaine, Eric R. [1 ]
机构
[1] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA 30602 USA
[2] Univ Toledo, Dept Med Microbiol & Immunol, Toledo, OH 43614 USA
关键词
D O I
10.1186/1471-2180-7-65
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Background: The Moraxella catarrhalis Hag protein, an Oca autotransporter adhesin, has previously been shown to be important for adherence of this respiratory tract pathogen to human middle ear and A549 lung cells. Results: The present study demonstrates that adherence of M. catarrhalis isogenic hag mutant strains to the human epithelial cell lines Chang (conjunctival) and NCIH292 (lung) is reduced by 50-93%. Furthermore, expressing Hag in a heterologous Escherichia coli background substantially increased the adherence of recombinant bacteria to NCIH292 cells and murine type IV collagen. Hag did not, however, increase the attachment of E. coli to Chang cells. These results indicate that Hag directly mediates adherence to NCIH292 lung cells and collagen, but is not sufficient to confer binding to conjunctival monolayers. Several in-frame deletions were engineered within the hag gene of M. catarrhalis strain O35E and the resulting proteins were tested for their ability to mediate binding to NCIH292 monolayers, middle ear cells, and type IV collagen. These experiments revealed that epithelial cell and collagen binding properties are separable, and that residues 385 705 of this similar to 2,000 amino acid protein are important for adherence to middle ear and NCIH292 cells. The region of O35E-Hag encompassing aa 706 to 1194 was also found to be required for adherence to collagen. In contrast, beta-roll repeats present in Hag, which are structural features conserved in several Oca adhesins and responsible for the adhesive properties of Yersinia enterocolitica YadA, are not important for Hag-mediated adherence. Conclusion: Hag is a major adherence factor for human cells derived from various anatomical sites relevant to pathogenesis by M. catarrhalis and its structure-function relationships differ from those of other, closely-related autotransporter proteins.
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页数:13
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共 59 条
[21]   Structure and sequence analysis of Yersinia YadA and Moraxella UspAs reveal a novel class of adhesins [J].
Hoiczyk, E ;
Roggenkamp, A ;
Reichenbecher, M ;
Lupas, A ;
Heesemann, J .
EMBO JOURNAL, 2000, 19 (22) :5989-5999
[22]   The Moraxella catarrhalis porin-like outer membrane protein CD is an adhesin for human lung cells [J].
Holm, MM ;
Vanlerberg, SL ;
Foley, IM ;
Sledjeski, DD ;
Lafontaine, ER .
INFECTION AND IMMUNITY, 2004, 72 (04) :1906-1913
[23]   The hag protein of Moraxella catarrhalis strain O35E is associated with adherence to human lung and middle ear cells [J].
Holm, MM ;
Vanlerberg, SL ;
Sledjeski, DD ;
Lafontaine, ER .
INFECTION AND IMMUNITY, 2003, 71 (09) :4977-4984
[24]   PILUS AND NONPILUS BACTERIAL ADHESINS - ASSEMBLY AND FUNCTION IN CELL RECOGNITION [J].
HULTGREN, SJ ;
ABRAHAM, S ;
CAPARON, M ;
FALK, P ;
STGEME, JW ;
NORMARK, S .
CELL, 1993, 73 (05) :887-901
[25]   Susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to 17 oral antimicrobial agents based on pharmacodynamic parameters:: 1998-2001 US Surveillance Study [J].
Jacobs, MR ;
Bajaksouzian, S ;
Windau, A ;
Good, CE ;
Lin, GR ;
Pankuch, GA ;
Appelbaum, PC .
CLINICS IN LABORATORY MEDICINE, 2004, 24 (02) :503-+
[26]   The clinical relevance of in-vitro resistance to penicillin, ampicillin, amoxycillin and alternative agents, for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis [J].
Klugman, KP .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1996, 38 :133-140
[27]   The UspA1 protein and a second type of UspA2 protein mediate adherence of Moraxella catarrhalis to human epithelial cells in vitro [J].
Lafontaine, ER ;
Cope, LD ;
Aebi, C ;
Latimer, JL ;
McCracken, GH ;
Hansen, EJ .
JOURNAL OF BACTERIOLOGY, 2000, 182 (05) :1364-1373
[28]   Expression of the Moraxella catarrhalis UspA1 protein undergoes phase variation and is regulated at the transcriptional level [J].
Lafontaine, ER ;
Wagner, NJ ;
Hansen, EJ .
JOURNAL OF BACTERIOLOGY, 2001, 183 (05) :1540-1551
[29]   Vaccination with FimH adhesin protects cynomolgus monkeys from colonization and infection by uropathogenic Escherichia coli [J].
Langermann, S ;
Möllby, R ;
Burlein, JE ;
Palaszynski, SR ;
Auguste, CG ;
DeFusco, A ;
Strouse, R ;
Schenerman, MA ;
Hultgren, SJ ;
Pinkner, JS ;
Winberg, J ;
Guldevall, L ;
Söderhäll, M ;
Ishikawa, K ;
Normark, S ;
Koenig, S .
JOURNAL OF INFECTIOUS DISEASES, 2000, 181 (02) :774-778
[30]   Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination [J].
Langermann, S ;
Palaszynski, S ;
Barnhart, M ;
Auguste, G ;
Pinkner, JS ;
Burlein, J ;
Barren, P ;
Koenig, S ;
Leath, S ;
Jones, CH ;
Hultgren, SJ .
SCIENCE, 1997, 276 (5312) :607-611