Evidence map›Paper›PMID 24747580›Full record

ArticleJournal of theoretical biology2014

Phase variation and host immunity against high molecular weight (HMW) adhesins shape population dynamics of nontypeable Haemophilus influenzae within human hosts.

Gregg S Davis, Simeone Marino, Carl F Marrs, Janet R Gilsdorf, Suzanne Dawid, Denise E Kirschner

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of theoretical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Prevalence, distribution, and sequence diversity of hmwA among commensal and otitis media non-typeable Haemophilus influenzae.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2014
    Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Gregg S DavisDepartment of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: gsdavis@gwu.edu.
Simeone MarinoDepartment of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, 5641 Med Sci II SPC 5620, Ann Arbor, MI 48109, USA. Electronic address: simeonem@umich.edu.
Carl F MarrsDepartment of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: cfmarrs@umich.edu.
Janet R GilsdorfDepartment of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan Medical School, L2225 Women׳s Hospital, Ann Arbor, MI 48109, USA. Electronic address: gilsdorf@med.umich.edu.
Suzanne DawidDepartment of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, 5641 Med Sci II SPC 5620, Ann Arbor, MI 48109, USA; UMHS Pediatric Infectious Diseases, University of Michigan Health System, D5101 MPB, Ann Arbor, MI 48109, USA. Electronic address: sdawid@med.umich.edu.
Denise E KirschnerDepartment of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, 5641 Med Sci II SPC 5620, Ann Arbor, MI 48109, USA. Electronic address: kirschne@umich.edu.
University of Michigan–Ann Arbor · USWomen's Hospital · US

Funding

Molecular Mechanisms of Microbial Pathogenesis Training ProgramT32AI007528 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CARRUTHERS, VERNON BRUCE · 1998 to 2024
$6.8M
Predicting immune responses that correlate with protection against tuberculosisR01HL110811 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FLYNN, JOANNE L., KIRSCHNER, DENISE E · 2012 to 2016
$5.9M
Defining how the spectrum of latency affects reactivation of TBR01HL106804 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FLYNN, JOANNE L., KIRSCHNER, DENISE E · 2010 to 2013
$2.6M
A multi-scale model to predict outcomes of immunomodulation and drug therapy duriR01EB012579 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FLYNN, JOANNE L., KIRSCHNER, DENISE E · 2011 to 2014
$2.3M
Interdisciplinary Training Program in Infectious DiseasesT32AI049816 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOXMAN, BETSY · 2002 to 2011
$1.5M
NHLBI NIH HHS R01 HL106804NHLBI NIH HHS R01HL106804NHLBI NIH HHS R01 HL110811NHLBI NIH HHS R01HL110811NIAID NIH HHS AI007528NIAID NIH HHS T32 AI007528NIAID NIH HHS T32 AI049816NIBIB NIH HHS R01 EB012579NIBIB NIH HHS R01EB012579PHS HHS TA32A1049816
6 · The paper itself

Abstract

Nontypeable Haemophilus influenzae (NTHi) is a bacterium that resides within the human pharynx. Because NTHi is human-restricted, its long-term survival is dependent upon its ability to successfully colonize new hosts. Adherence to host epithelium, mediated by bacterial adhesins, is one of the first steps in NTHi colonization. NTHi express several adhesins, including the high molecular weight (HMW) adhesins that mediate attachment to the respiratory epithelium where they interact with the host immune system to elicit a strong humoral response. hmwA, which encodes the HMW adhesin, undergoes phase variation mediated by 7-base pair tandem repeats located within its promoter region. Repeat number affects both hmwA transcription and HMW-adhesin production such that as the number of repeats increases, adhesin production decreases. Cells expressing large amounts of HMW adhesins may be critical for the establishment and maintenance of NTHi colonization, but they might also incur greater fitness costs when faced with an adhesin-specific antibody-mediated immune response. We hypothesized that the occurrence of large deletion events within the hmwA repeat region allows NTHi cells to maintain adherence in the presence of antibody-mediated immunity. To study this, we developed a mathematical model, incorporating hmwA phase variation and antibody-mediated immunity, to explore the trade-off between bacterial adherence and immune evasion. The model predicts that antibody levels and avidity, catastrophic loss rates, and population carrying capacity all significantly affected numbers of adherent NTHi cells within a host. These results suggest that the occurrence of large, yet rare, deletion events allows for stable maintenance of a small population of adherent cells in spite of HMW adhesin specific antibody-mediated immunity. These adherent subpopulations may be important for sustaining colonization and/or maintaining transmission.

Indexed as

Immunity, HumoralModels, ImmunologicalAdhesins, BacterialAntibodies, BacterialHaemophilus InfectionsHaemophilus influenzaeHumansRespiratory MucosaAdhesins, BacterialAntibodies, BacterialAcute otitis media (AOM)Bacterial adherenceBacterial colonizationBacterial transmissionChronic obstructive pulmonary disease (COPD)

Identifiers

PMID24747580
PMCPMC4089356
OpenAlexW2078887713

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.