scholarly journals Phase-Variable Glycosylation in Nontypeable Haemophilus influenzae

2019 ◽  
Vol 19 (1) ◽  
pp. 464-476 ◽  
Author(s):  
Danila Elango ◽  
Benjamin L. Schulz
Keyword(s):  
Haemophilus Influenzae ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae

scholarly journals Analysis of Nontypeable Haemophilus influenzae Phase-Variable Genes During Experimental Human Nasopharyngeal Colonization

2013 ◽  
Vol 208 (5) ◽  
pp. 720-727 ◽  
Author(s):  
Jessica Poole ◽  
Eric Foster ◽  
Kathryn Chaloner ◽  
Jason Hunt ◽  
Michael P. Jennings ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae ◽  
Nasopharyngeal Colonization ◽  
Variable Genes

scholarly journals Closed Complete Genome Sequences of Two Nontypeable Haemophilus influenzae Strains Containing Novel modA Alleles from the Sputum of Patients with Chronic Obstructive Pulmonary Disease

2018 ◽  
Vol 7 (2) ◽  
Author(s):  
John M. Atack ◽  
Timothy F. Murphy ◽  
Lauren O. Bakaletz ◽  
Kate L. Seib ◽  
Michael P. Jennings
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Haemophilus Influenzae ◽  
Pulmonary Disease ◽  
Complete Genome ◽  
Chronic Obstructive ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae ◽  
Genome Sequences ◽  
Obstructive Pulmonary Disease ◽  
Content Type

Nontypeable Haemophilus influenzae (NTHi) is an important bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease (COPD). Here, we report the complete genome sequences of NTHi strains 10P129H1 and 84P36H1, isolated from COPD patients, which contain the phase-variable epigenetic regulators ModA15 and ModA18, respectively.

scholarly journals Phosphorylcholine Decreases Early Inflammation and Promotes the Establishment of Stable Biofilm Communities of Nontypeable Haemophilus influenzae Strain 86-028NP in a Chinchilla Model of Otitis Media

2006 ◽  
Vol 75 (2) ◽  
pp. 958-965 ◽  
Author(s):  
Wenzhou Hong ◽  
Kevin Mason ◽  
Joseph Jurcisek ◽  
Laura Novotny ◽  
Lauren O. Bakaletz ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Fluorescent Antibody ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae ◽  
Bacterial Surface ◽  
Culture Cells ◽  
Antibody Staining

ABSTRACT Nontypeable Haemophilus influenzae (NTHi) is a leading causative agent of otitis media. Much of the inflammation occurring during NTHi disease is initiated by lipooligosaccharides (LOS) on the bacterial surface. Phosphorylcholine (PCho) is added to some LOS forms in a phase-variable manner, and these PCho+ variants predominate in vivo. Thus, we asked whether this modification confers some advantage during infection. Virulence of an otitis media isolate (NTHi strain 86-028NP) was compared with that of an isogenic PCho transferase (licD) mutant using a chinchilla (Chinchilla lanigera) model of otitis media. Animals infected with NTHi 86-028NP licD demonstrated increased early inflammation and a delayed increase in bacterial counts compared to animals infected with NTHi 86-028NP. LOS purified from chinchilla-passed NTHi 86-028NP had increased PCho content compared to LOS purified from the inoculum. Both strains were recovered from middle ear fluids as long as 14 days postinfection. Biofilms were macroscopically visible in the middle ears of euthanized animals infected with NTHi 86-028NP 7 days and 14 days postchallenge. Conversely, less dense biofilms were observed in animals infected with NTHi 86-028NP licD 7 days postinfection, and none of the animals infected with NTHi 86-028NP licD had a visible biofilm by 14 days. Fluorescent antibody staining revealed PCho+ variants within biofilms, similar to our prior results with tissue culture cells in vitro (S. L. West-Barnette, A. Rockel, and W. E. Swords, Infect. Immun. 74:1828-1836, 2006). Animals coinfected with equal proportions of both strains had equal persistence of each strain and somewhat greater severity of disease. We thus conclude that PCho promotes NTHi infection and persistence by reducing the host inflammatory response and by promoting formation of stable biofilm communities.

scholarly journals High-Depth RNA-Seq Data Sets for Studying Gene Expression Changes Mediated by Phase-Variable DNA Methyltransferases in Nontypeable Haemophilus influenzae

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
John M. Atack ◽  
Lauren O. Bakaletz ◽  
Michael P. Jennings
Keyword(s):  
Haemophilus Influenzae ◽  
Bacterial Pathogen ◽  
Dna Methyltransferases ◽  
Multiple Infections ◽  
Data Sets ◽  
Phase Variable ◽  
Rna Seq ◽  
Nontypeable Haemophilus Influenzae ◽  
Content Type ◽  
High Depth

Nontypeable Haemophilus influenzae (NTHi) is a major bacterial pathogen that causes multiple infections. We report high-depth-coverage RNA-Seq data from three NTHi strains, each of which encodes a different phase-variable methyltransferase.

scholarly journals Underlying Glycans Determine the Ability of Sialylated Lipooligosaccharide To Protect Nontypeable Haemophilus influenzae from Serum IgM and Complement

2019 ◽  
Vol 87 (11) ◽  
Author(s):  
Mary Darby Jackson ◽  
Sandy M. Wong ◽  
Brian J. Akerley
Keyword(s):  
Sialic Acid ◽  
Haemophilus Influenzae ◽  
Phase Variation ◽  
Population Diversity ◽  
Classical Pathway ◽  
Immune Recognition ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae ◽  
Content Type ◽  
Complex Glycans

ABSTRACT Nontypeable Haemophilus influenzae (NTHi) efficiently colonizes the human nasopharynx asymptomatically but also causes respiratory mucosal infections, including otitis media, sinusitis, and bronchitis. The lipooligosaccharide (LOS) on the cell surface of NTHi displays complex glycans that mimic host structures, allowing it to evade immune recognition. However, LOS glycans are also targets of host adaptive and innate responses. To aid in evasion of these responses, LOS structures exhibit interstrain heterogeneity and are also subject to phase variation, the random on/off switching of gene expression, generating intrastrain population diversity. Specific LOS modifications, including terminal sialylation of the LOS, which exploits host-derived sialic acid (Neu5Ac), can also block recognition of NTHi by bactericidal IgM and complement by mechanisms that are not fully understood. We investigated the LOS sialic acid-mediated resistance of NTHi to antibody-directed killing by serum complement. We identified specific LOS structures extending from heptose III that are targets for binding by naturally occurring bactericidal IgM in serum and are protected by sialylation of the LOS. Phase-variable galactosyltransferases encoded by lic2A and lgtC each add a galactose epitope bound by IgM that results in antibody-dependent killing via the classical pathway of complement. NTHi’s survival can be influenced by the expression of phase-variable structures on the LOS that may also depend on environmental conditions, such as the availability of free sialic acid. Identification of surface structures on NTHi representing potential targets for antibody-based therapies as alternatives to antibiotic treatment would thus be valuable for this medically important pathogen.

Mecanismos moleculares de adaptación del patógeno respiratorio Haemophilus influenzae y desarrollo de nuevos antimicrobianos

2020 ◽  
Author(s):  
◽  
Ariadna Fernández Calvet
Keyword(s):  
Haemophilus Influenzae ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Phase Variation ◽  
Opportunistic Pathogen ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae ◽  
Molecular Systems ◽  
Bacterial Surface ◽  
Human Airways

This PhD Thesis work tackled three aspects of the interaction between the colonizing opportunistic pathogen nontypeable Haemophilus influenzae (NTHi) and the human airways, by considering the concepts of phase-variable regulation of pathoadaptive traits (Chapter 1), the importance of molecular systems involved in maintaining the bacterial surface integrity (Chapter 2), and the therapeutic potential of xenohormetic molecules (Chapter 3). Altogether, this work contributes expanding our understanding on molecular mechanisms of NTHi pathoadaptation regulated by phase variation, provides evidence for VacJ/MlaA as a key bacterial factor modulating NTHi survival at the human airway upon exposure to hydrophobic molecules, and highlights the therapeutic potential of xenohormetic molecules against NTHi infection.

scholarly journals Shielding of a Lipooligosaccharide IgM Epitope Allows Evasion of Neutrophil-Mediated Killing of an Invasive Strain of Nontypeable Haemophilus influenzae

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Jeroen D. Langereis ◽  
Jeffrey N. Weiser
Keyword(s):  
Haemophilus Influenzae ◽  
Immune Cells ◽  
Inner Core ◽  
Inflammatory Diseases ◽  
White Blood Cells ◽  
Human Neutrophils ◽  
Chronic Obstructive ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae ◽  
Content Type

ABSTRACTNontypeableHaemophilus influenzaeis a frequent cause of noninvasive mucosal inflammatory diseases but may also cause invasive diseases, such as sepsis and meningitis, especially in children and the elderly. Infection by nontypeableHaemophilus influenzaeis characterized by recruitment of neutrophilic granulocytes. Despite the presence of a large number of neutrophils, infections with nontypeableHaemophilus influenzaeare often not cleared effectively by the antimicrobial activity of these immune cells. Herein, we examined how nontypeableHaemophilus influenzaeevades neutrophil-mediated killing. Transposon sequencing (Tn-seq) was used on an isolate resistant to neutrophil-mediated killing to identify genes required for its survival in the presence of human neutrophils and serum, which provided a source of complement and antibodies. Results show that nontypeableHaemophilus influenzaeprevents complement-dependent neutrophil-mediated killing by expression of surface galactose-containing oligosaccharide structures. These outer-core structures block recognition of an inner-core lipooligosaccharide epitope containing glucose attached to heptose HepIII-β1,2-Glc by replacement with galactose attached to HepIII or through shielding HepIII-β1,2-Glc by phase-variable attachment of oligosaccharide chain extensions. When the HepIII-β1,2-Glc-containing epitope is expressed and exposed, nontypeableHaemophilus influenzaeis opsonized by naturally acquired IgM generally present in human serum and subsequently phagocytosed and killed by human neutrophils. Clinical nontypeableHaemophilus influenzaeisolates containing galactose attached to HepIII that are not recognized by this IgM are more often found to cause invasive infections.IMPORTANCENeutrophils are white blood cells that specialize in killing pathogens and are recruited to sites of inflammation. However, despite the presence of large numbers of neutrophils in the middle ear cavity and lungs of patients with otitis media or chronic obstructive pulmonary disease, respectively, the bacterium nontypeableHaemophilus influenzaeis often not effectively cleared from these locations by these immune cells. In order to understand how nontypeableHaemophilus influenzaeis able to cause inflammatory diseases in the presence of neutrophils, we determined the mechanism that underlies resistance to neutrophil-mediated killing. We have shown that nontypeableHaemophilus influenzaeprevents binding of antibodies of the IgM subtype through changes in their surface lipooligosaccharide structure, thereby preventing complement activation and clearance by human neutrophils.

scholarly journals Antisera Against Certain Conserved Surface-Exposed Peptides of Nontypeable Haemophilus influenzae Are Protective

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0136867 ◽  
Author(s):  
Paul W. Whitby ◽  
Thomas W. Seale ◽  
Daniel J. Morton ◽  
Terrence L. Stull
Keyword(s):  
Haemophilus Influenzae ◽  
Nontypeable Haemophilus Influenzae
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