Evidence map›Paper›PMID 32692363›Full record

ArticleThe Journal of infectious diseases2020

Efficacy of Antigonococcal CMP-Nonulosonate Therapeutics Require Cathelicidins.

Sunita Gulati, Ian C Schoenhofen, Theresa Lindhout-Djukic, Lisa A Lewis, Iesha Y Moustafa, Sudeshna Saha, Bo Zheng, Nancy Nowak, Peter A Rice, Ajit Varki and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 22% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. mBio · 2024
    Article
  6. Review
  7. bioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Anti-Virulence Therapeutic Approaches forAntibiotics (Basel, Switzerland) · 2021
    Review
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Sunita GulatiDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Ian C SchoenhofenHuman Health Therapeutics Research Centre, National Research Council of Canada, Ottawa, Ontario, Canada.
Theresa Lindhout-DjukicHuman Health Therapeutics Research Centre, National Research Council of Canada, Ottawa, Ontario, Canada.
Lisa A LewisDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Iesha Y MoustafaDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Sudeshna SahaDepartment of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California, USA.
Bo ZhengDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Nancy NowakDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Peter A RiceDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Ajit VarkiDepartment of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California, USA.
Sanjay RamDivision of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
University of Massachusetts Chan Medical School · USNational Research Council Canada · CAUniversity of California, San Diego · US

Funding

BIOSYNTHESIS AND REGULATION OF SUBSTITUTED SIALIC ACIDSR01GM032373 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARKI, AJIT P · 1985 to 2022
$6.9M
Immune defenses against Neisseria gonorrhoeaeR01AI114790 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI RAM, SANJAY, RICE, PETER A. · 2015 to 2019
$3.1M
Sialic acid analogs as novel immunotherapeutics against multidrug-resistant gonorrheaR33AI119327 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GULATI, SUNITA, RAM, SANJAY · 2017 to 2019
$1.4M
NIAID NIH HHS R01 AI114790NIAID NIH HHS R33 AI119327NIGMS NIH HHS R01 GM032373
6 · The paper itself

Abstract

Novel therapies to counteract multidrug-resistant gonorrhea are urgently needed. A unique gonococcal immune evasion strategy involves capping of lipooligosaccharide (LOS) with sialic acid by gonococcal sialyltransferase (Lst), utilizing host-derived CMP-sialic acid (CMP-Neu5Ac in humans). LOS sialylation renders gonococci resistant to complement and cationic peptides, and down-regulates the inflammatory response by engaging siglecs. CMP-sialic acid analogs (CMP-nonulosonates [CMP-NulOs]) such as CMP-Leg5,7Ac2 and CMP-Kdn are also utilized by Lst. Incorporation of these NulO analogs into LOS maintains gonococci susceptible to complement. Intravaginal administration of CMP-Kdn or CMP-Leg5,7Ac2 attenuates gonococcal colonization of mouse vaginas. Here, we identify a key mechanism of action for the efficacy of CMP-NulOs. Surprisingly, CMP-NulOs remained effective in complement C1q-/- and C3-/- mice. LOS Neu5Ac, but not Leg5,7Ac2 or Kdn, conferred resistance to the cathelicidins LL-37 (human) and mouse cathelicidin-related antimicrobial peptide in vitro. CMP-NulOs were ineffective in Camp-/- mice, revealing that cathelicidins largely mediate the efficacy of therapeutic CMP-NulOs.

Indexed as

AnimalsAntimicrobial Cationic PeptidesCathelicidinsComplement System ProteinsCytidine MonophosphateFemaleGonorrheaLipopolysaccharidesMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutN-Acetylneuraminic AcidNeisseria gonorrhoeaeNeuraminic AcidsSialic AcidsAntimicrobial Cationic PeptidesCathelicidinsCMP-deaminoneuraminic acidComplement System Proteinscytidine-5'-monophosphosialic acidCytidine Monophosphatelipid-linked oligosaccharidesLipopolysaccharidesN-Acetylneuraminic AcidNeuraminic AcidsSialic AcidsSialyltransferasescathelicidincationic antimicrobial peptideCMP-nonulosonatecomplementgonorrhealipooligosaccharideNeisseria gonorrhoeaesialic acid

Identifiers

PMID32692363
PMCPMC7552427
OpenAlexW3045276811

What OpenQuestion holds

Textmetadata
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.