Evidence map›Paper›PMID 25902140›Full record

ArticlePloS one2015

Phosphoethanolamine Transferase LptA in Haemophilus ducreyi Modifies Lipid A and Contributes to Human Defensin Resistance In Vitro.

Michael P Trombley, Deborah M B Post, Sherri D Rinker, Lorri M Reinders, Kate R Fortney, Beth W Zwickl, Diane M Janowicz, Fitsum M Baye, Barry P Katz, Stanley M Spinola and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Molecular pathogenesis ofMicrobiology and molecular biology reviews : MMBR · 2025
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  11. Interactions of the Skin PathogenFrontiers in immunology · 2020
    Review
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  16. Identification ofFrontiers in microbiology · 2017
    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

11 authors at 3 institutions in 1 country.

Michael P TrombleyDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Deborah M B PostBuck Institute for Research on Aging, Novato, CA, United States of America.
Sherri D RinkerDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Lorri M ReindersBuck Institute for Research on Aging, Novato, CA, United States of America.
Kate R FortneyDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Beth W ZwicklDepartment of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Diane M JanowiczDepartment of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Fitsum M BayeDepartment of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, United States of America; Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indianapolis, IN, United States of America.
Barry P KatzDepartment of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, United States of America; Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indianapolis, IN, United States of America.
Stanley M SpinolaDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States of America; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States of America; Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Margaret E BauerDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Indiana University – Purdue University Indianapolis · USIndiana University School of MedicineBuck Institute for Research on Aging · US

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
Immunology and Infectious Diseases Training ProgramT32AI060519 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MARK H KAPLAN · 2004 to 2026
$6.0M
LIPOOLIGOSACCHARIDES OF HAEMOPHILUS INFLUENZAER01AI024616 · NIAID · UNIVERSITY OF IOWA · PI APICELLA, MICHAEL A. · 1988 to 2014
$6.0M
PATHOGENESIS OF HAEMOPHILUS DUCREYI INFECTIONSR01AI027863 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SPINOLA, STANLEY M. · 1995 to 2013
$3.8M
Structural Characterization of Polypeptides, Protein Complexes, OligosaccharidesS10RR029446 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WITKOWSKA, H. EWA · 2010 to 2010
$1.0M
Mechanisms of Sap-mediated Antimicrobial Peptide ResistanceR21AI096056 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI BAUER, MARGARET E · 2011 to 2012
$424k
NCATS NIH HHS UL1 TR001108NCRR NIH HHS 1S10RR029446NCRR NIH HHS S10 RR029446NCRR NIH HHS UL RR052761NIAID NIH HHS R01 AI024616NIAID NIH HHS R01 AI027863NIAID NIH HHS R21 AI096056NIAID NIH HHS T32 AI060519
6 · The paper itself

Abstract

Haemophilus ducreyi resists the cytotoxic effects of human antimicrobial peptides (APs), including α-defensins, β-defensins, and the cathelicidin LL-37. Resistance to LL-37, mediated by the sensitive to antimicrobial peptide (Sap) transporter, is required for H. ducreyi virulence in humans. Cationic APs are attracted to the negatively charged bacterial cell surface. In other gram-negative bacteria, modification of lipopolysaccharide or lipooligosaccharide (LOS) by the addition of positively charged moieties, such as phosphoethanolamine (PEA), confers AP resistance by means of electrostatic repulsion. H. ducreyi LOS has PEA modifications at two sites, and we identified three genes (lptA, ptdA, and ptdB) in H. ducreyi with homology to a family of bacterial PEA transferases. We generated non-polar, unmarked mutants with deletions in one, two, or all three putative PEA transferase genes. The triple mutant was significantly more susceptible to both α- and β-defensins; complementation of all three genes restored parental levels of AP resistance. Deletion of all three PEA transferase genes also resulted in a significant increase in the negativity of the mutant cell surface. Mass spectrometric analysis revealed that LptA was required for PEA modification of lipid A; PtdA and PtdB did not affect PEA modification of LOS. In human inoculation experiments, the triple mutant was as virulent as its parent strain. While this is the first identified mechanism of resistance to α-defensins in H. ducreyi, our in vivo data suggest that resistance to cathelicidin LL-37 may be more important than defensin resistance to H. ducreyi pathogenesis.

Indexed as

Administration, OralAdultalpha-DefensinsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacterial Proteinsbeta-DefensinsCathelicidinsChancroidCiprofloxacinDrug Resistance, BacterialEthanolaminephosphotransferaseEthanolaminesFemaleGene DeletionGene Expressionalpha-DefensinsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacterial Proteinsbeta-DefensinsCathelicidinsCiprofloxacinEthanolaminephosphotransferaseEthanolaminesLipid Aphosphorylethanolamine

Identifiers

PMID25902140
PMCPMC4406763
OpenAlexW2046151891

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.