Molecular Mechanism of Haemophilus influenzae Pathogenicity

2015 ◽  
pp. 30-51 ◽  
Author(s):  
Vicky C. Liu ◽  
Arnold L. Smith
Keyword(s):  
Haemophilus Influenzae ◽  
Molecular Mechanism

scholarly journals Modified Lipooligosaccharide Structure Protects Nontypeable Haemophilus influenzae from IgM-Mediated Complement Killing in Experimental Otitis Media

mBio ◽  
2012 ◽  
Vol 3 (4) ◽  
Author(s):  
Jeroen D. Langereis ◽  
Kim Stol ◽  
Elke K. Schweda ◽  
Brigitte Twelkmeyer ◽  
Hester J. Bootsma ◽  
...  
Keyword(s):  
Mouse Model ◽  
Haemophilus Influenzae ◽  
Molecular Mechanism ◽  
Otitis Media ◽  
Middle Ear ◽  
Crucial Role ◽  
Influenza A ◽  
Gram Negative ◽  
Content Type ◽  
Complement Resistance

ABSTRACTNontypeableHaemophilus influenzae(NTHi) is a Gram-negative, human-restricted pathogen. Although this bacterium typically colonizes the nasopharynx in the absence of clinical symptoms, it is also one of the major pathogens causing otitis media (OM) in children. Complement represents an important aspect of the host defense against NTHi. In general, NTHi is efficiently killed by complement-mediated killing; however, various resistance mechanisms have also evolved. We measured the complement resistance of NTHi isolates isolated from the nasopharynx and the middle ear fluids of OM patients. Furthermore, we determined the molecular mechanism of NTHi complement resistance. Complement resistance was strongly increased in isolates from the middle ear, which correlated with decreased binding of IgM. We identified a crucial role for the R2866_0112 gene in complement resistance. Deletion of this gene altered the lipooligosaccharide (LOS) composition of the bacterium, which increased IgM binding and complement-mediated lysis. In a novel mouse model of coinfection with influenza virus, we demonstrate decreased virulence for the R2866_0112 deletion mutant. These findings identify a mechanism by which NTHi modifies its LOS structure to prevent recognition by IgM and activation of complement. Importantly, this mechanism plays a crucial role in the ability of NTHi to cause OM.IMPORTANCENontypeableHaemophilus influenzae(NTHi) colonizes the nasopharynx of especially young children without any obvious symptoms. However, NTHi is also a major pathogen in otitis media (OM), one of the most common childhood infections. Although this pathogen is often associated with OM, the mechanism by which this bacterium is able to cause OM is largely unknown. Our study addresses a key biological question that is highly relevant for child health: what is the molecular mechanism that enables NTHi to cause OM? We show that isolates collected from the middle ear fluid exhibit increased complement resistance and that the lipooligosaccharide (LOS) structure determines IgM binding and complement activation. Modification of the LOS structure decreased NTHi virulence in a novel NTHi-influenza A virus coinfection OM mouse model. Our findings may also have important implications for other Gram-negative pathogens harboring LOS, such asNeisseria meningitidis,Moraxella catarrhalis, andBordetella pertussis.

Ultrastructural studies on the interaction of haemophilus influenzae with human endothelial cells in vitro

1990 ◽  
Vol 48 (3) ◽  
pp. 636-637
Author(s):  
D.J.P. Ferguson ◽  
M. Virji ◽  
H. Kayhty ◽  
E.R. Moxon
Keyword(s):  
Endothelial Cells ◽  
Haemophilus Influenzae ◽  
Intercellular Junctions ◽  
Blood Stream ◽  
Ultrastructural Studies ◽  
Endothelial Barriers ◽  
Serotype B ◽  
Meningitis In Children ◽  
Respiratory Epithelial

Haemophilus influenzae is a human pathogen which causes meningitis in children. Systemic H. influenzae infection is largely confined to encapsulated serotype b organisms and is a major cause of meningitis in the U.K. and elsewhere. However, the pathogenesis of the disease is still poorly understood. Studies in the infant rat model, in which intranasal challenge results in bacteraemia, have shown that H. influenzae enters submucosal tissues and disseminates to the blood stream within minutes. The rapidity of these events suggests that H. influenzae penetrates both respiratory epithelial and endothelial barriers with great efficiency. It is not known whether the bacteria penetrate via the intercellular junctions, are translocated within the cells or carried across the cellular barrier in 'trojan horse' fashion within phagocytes. In the present studies, we have challenged cultured human umbilical cord_vein endothelial cells (HUVECs) with both capsulated (b+) and capsule-deficient (b-) isogenic variants of one strain of H. influenzae in order to investigate the interaction between the bacteria and HUVEC and the effect of the capsule.

Additional evidence for AQP1 vesicle trafficking as a molecular mechanism for ductal bile secretion

2001 ◽  
Vol 120 (5) ◽  
pp. A91-A91
Author(s):  
P TIETZ ◽  
P SPLINTER ◽  
M MCNIVEN ◽  
R HUEBERT ◽  
N LARUSSO
Keyword(s):  
Molecular Mechanism ◽  
Vesicle Trafficking ◽  
Bile Secretion

Hypoxia/Reoxygenation on human myometrial and decidual cells: A molecular mechanism involved in preterra labor

1998 ◽  
Vol 5 (1) ◽  
pp. 187A-187A
Author(s):  
J CARVAJAL ◽  
S KATO ◽  
J SAEZ ◽  
F LEIGHTON ◽  
G VALENZUELA ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Decidual Cells ◽  
Hypoxia Reoxygenation

Molecular Mechanism of Apoptosis Induction by Resveratrol, a Natural Cancer Chemopreventive Agent

2008 ◽  
Vol 78 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Fan ◽  
Jiang ◽  
Zhang ◽  
Bai
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanism ◽  
Apoptosis Induction ◽  
Protective Agents ◽  
Chemopreventive Agent ◽  
Naturally Occurring ◽  
Apoptosis Pathways ◽  
Present Understanding

In efforts to identify naturally occurring compounds that act as protective agents, resveratrol, a phytoalexin existing in wine, has attracted much interest because of its diverse pharmacological characteristics. Considering that apoptosis induction is the most potent defense approach for cancer treatment, we have tried to summarize our present understanding of apoptosis induction by resveratrol based on the two major apoptosis pathways.

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