PMID- 24835392
OWN - NLM
STAT- MEDLINE
DCOM- 20140818
LR  - 20140609
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 192
IP  - 12
DP  - 2014 Jun 15
TI  - Identification of a Haemophilus influenzae factor H-Binding lipoprotein involved 
      in serum resistance.
PG  - 5913-23
LID - 10.4049/jimmunol.1303449 [doi]
AB  - 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.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - Fleury, Christophe
AU  - Fleury C
AD  - Medical Microbiology, Department of Laboratory Medicine Malmo, Lund University, 
      SE-205 02 Malmo, Sweden;
FAU - Su, Yu-Ching
AU  - Su YC
AD  - Medical Microbiology, Department of Laboratory Medicine Malmo, Lund University, 
      SE-205 02 Malmo, Sweden;
FAU - Hallstrom, Teresia
AU  - Hallstrom T
AD  - Department of Infection Biology, Leibniz Institute for Natural Product Research 
      and Infection Biology, Faculty of Biology, Friedrich Schiller University, 07745 
      Jena, Germany; and.
FAU - Sandblad, Linda
AU  - Sandblad L
AD  - Department of Molecular Biology, Umea University, SE-901 87 Umea, Sweden.
FAU - Zipfel, Peter F
AU  - Zipfel PF
AD  - Department of Infection Biology, Leibniz Institute for Natural Product Research 
      and Infection Biology, Faculty of Biology, Friedrich Schiller University, 07745 
      Jena, Germany; and.
FAU - Riesbeck, Kristian
AU  - Riesbeck K
AD  - Medical Microbiology, Department of Laboratory Medicine Malmo, Lund University, 
      SE-205 02 Malmo, Sweden; kristian.riesbeck@med.lu.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140516
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Bacterial Proteins)
RN  - 0 (Lipoproteins)
RN  - 0 (Recombinant Proteins)
RN  - 80295-65-4 (Complement Factor H)
SB  - IM
MH  - Bacterial Proteins/chemistry/genetics/*immunology
MH  - Blood Bactericidal Activity/*immunology
MH  - Complement Factor H/*immunology
MH  - Female
MH  - Haemophilus influenzae/chemistry/genetics/*immunology
MH  - Humans
MH  - Lipoproteins/chemistry/genetics/*immunology
MH  - Male
MH  - Mutation
MH  - Recombinant Proteins/chemistry/genetics/immunology
EDAT- 2014/05/20 06:00
MHDA- 2014/08/19 06:00
CRDT- 2014/05/20 06:00
PHST- 2014/05/20 06:00 [entrez]
PHST- 2014/05/20 06:00 [pubmed]
PHST- 2014/08/19 06:00 [medline]
AID - jimmunol.1303449 [pii]
AID - 10.4049/jimmunol.1303449 [doi]
PST - ppublish
SO  - J Immunol. 2014 Jun 15;192(12):5913-23. doi: 10.4049/jimmunol.1303449. Epub 2014 
      May 16.