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Identification of a Haemophilus influenzae Factor H-Binding Lipoprotein Involved in Serum Resistance.

Fleury, Christophe LU ; Su, Shanice YC LU ; Hallström, Teresia LU ; Sandblad, Linda; Zipfel, Peter F and Riesbeck, Kristian LU (2014) In Journal of Immunology 192(12). p.5913-5923
Abstract
Haemophilus influenzae is a Gram-negative human pathogen that resides in the upper respiratory tract. Encapsulated H. influenzae type b (Hib) and type f (Hif) are the most common serotypes associated with invasive disease. H. influenzae displays various strategies to circumvent the host innate immune response, including the bactericidal effect of the complement system. In this study, we identified an H. influenzae lipoprotein having the ability to bind factor H (FH), the major regulator of the alternative pathway of complement activation. This protein, named protein H (PH), was surface exposed and was found in all clinical Hib and Hif isolates tested. Deletion of the gene encoding for PH (lph) in Hib and Hif significantly reduced the... (More)
Haemophilus influenzae is a Gram-negative human pathogen that resides in the upper respiratory tract. Encapsulated H. influenzae type b (Hib) and type f (Hif) are the most common serotypes associated with invasive disease. H. influenzae displays various strategies to circumvent the host innate immune response, including the bactericidal effect of the complement system. In this study, we identified an H. influenzae lipoprotein having the ability to bind factor H (FH), the major regulator of the alternative pathway of complement activation. This protein, named protein H (PH), was surface exposed and was found in all clinical Hib and Hif isolates tested. Deletion of the gene encoding for PH (lph) in Hib and Hif significantly reduced the interaction between bacteria and FH. When Hib and Hif PH variants were separately expressed in nontypeable (unencapsulated) H. influenzae, which did not bind FH, an increased FH affinity was observed. We recombinantly expressed the two PH variants in Escherichia coli, and despite sharing only 56% identical amino acids, both FH-binding Haemophilus proteins similarly interacted with the complement regulator FH short consensus repeats 7 and 18-20. Importantly, Hib and Hif resistance against the bactericidal effect of human serum was significantly reduced when bacterial mutants devoid of PH were tested. In conclusion, we have characterized a hitherto unknown bacterial protein that is crucial for mediating an interaction between the human pathogen H. influenzae and FH. This novel interaction is important for H. influenzae resistance against complement activation and will consequently promote bacterial pathogenesis. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
192
issue
12
pages
5913 - 5923
publisher
American Association of Immunologists
external identifiers
  • pmid:24835392
  • wos:000337172100051
  • scopus:84902172649
ISSN
1550-6606
DOI
10.4049/jimmunol.1303449
language
English
LU publication?
yes
id
e37baff0-9fe2-4fc9-8397-73433fa10364 (old id 4454391)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24835392?dopt=Abstract
date added to LUP
2014-06-04 21:01:52
date last changed
2017-08-27 03:44:23
@article{e37baff0-9fe2-4fc9-8397-73433fa10364,
  abstract     = {Haemophilus influenzae is a Gram-negative human pathogen that resides in the upper respiratory tract. Encapsulated H. influenzae type b (Hib) and type f (Hif) are the most common serotypes associated with invasive disease. H. influenzae displays various strategies to circumvent the host innate immune response, including the bactericidal effect of the complement system. In this study, we identified an H. influenzae lipoprotein having the ability to bind factor H (FH), the major regulator of the alternative pathway of complement activation. This protein, named protein H (PH), was surface exposed and was found in all clinical Hib and Hif isolates tested. Deletion of the gene encoding for PH (lph) in Hib and Hif significantly reduced the interaction between bacteria and FH. When Hib and Hif PH variants were separately expressed in nontypeable (unencapsulated) H. influenzae, which did not bind FH, an increased FH affinity was observed. We recombinantly expressed the two PH variants in Escherichia coli, and despite sharing only 56% identical amino acids, both FH-binding Haemophilus proteins similarly interacted with the complement regulator FH short consensus repeats 7 and 18-20. Importantly, Hib and Hif resistance against the bactericidal effect of human serum was significantly reduced when bacterial mutants devoid of PH were tested. In conclusion, we have characterized a hitherto unknown bacterial protein that is crucial for mediating an interaction between the human pathogen H. influenzae and FH. This novel interaction is important for H. influenzae resistance against complement activation and will consequently promote bacterial pathogenesis.},
  author       = {Fleury, Christophe and Su, Shanice YC and Hallström, Teresia and Sandblad, Linda and Zipfel, Peter F and Riesbeck, Kristian},
  issn         = {1550-6606},
  language     = {eng},
  number       = {12},
  pages        = {5913--5923},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Identification of a Haemophilus influenzae Factor H-Binding Lipoprotein Involved in Serum Resistance.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1303449},
  volume       = {192},
  year         = {2014},
}