Evidence map›Paper›PMID 26619249›Full record

ArticleNature chemical biology2016

A synthetic lethal approach for compound and target identification in Staphylococcus aureus.

Lincoln Pasquina, John P Santa Maria, B McKay Wood, Samir H Moussa, Leigh M Matano, Marina Santiago, Sara E S Martin, Wonsik Lee, Timothy C Meredith, Suzanne Walker

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

52 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
  2. Article
  3. Mechanistic study on the susceptibility ofApplied and environmental microbiology · 2025
    Article
  4. SpbR controls lipoteichoic acid length by directly inhibiting signal peptidase SpsB inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  18. Rapid Inhibitor Discovery by Exploiting Synthetic Lethality.Journal of the American Chemical Society · 2022
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Lincoln PasquinaDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
John P Santa MariaDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
B McKay WoodDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Samir H MoussaDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Leigh M MatanoDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Marina SantiagoDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Sara E S MartinDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Wonsik LeeDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Timothy C MeredithDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Suzanne WalkerDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Harvard University · USPennsylvania State University · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WHELAN, SEAN PJ · 2003 to 2013
$113.7M
Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Michael S Gilmore · 2009 to 2026
$39.4M
Targeting bacterial cell wall biogenesis for the development of novel antimicrobU19AI109764 · NIAID · HARVARD MEDICAL SCHOOL · PI KASPER, DENNIS L. · 2014 to 2018
$25.2M
INFECTIOUS DISEASE AND BASIC MICROBIOLOGICAL MECHANISMST32AI007061 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Marcia B Goldberg · 1985 to 2026
$12.1M
Identifying and validating new antibiotic targets in cell wall synthesis pathwaysR01AI099144 · NIAID · HARVARD MEDICAL SCHOOL · PI BERNHARDT, THOMAS G, WALKER, SUZANNE · 2012 to 2016
$4.3M
The role of putative membrane proteases in S. aureus cell divisionF32AI118160 · NIAID · HARVARD MEDICAL SCHOOL · PI MOUSSA, SAMIR · 2015 to 2015
$34k
Probing with a panel of beta-lactams to find genetic resistance factors in MRSAF31AI114131 · NIAID · HARVARD MEDICAL SCHOOL · PI SANTIAGO, MARINA · 2015 to 2015
$31k
NIAID NIH HHS F31 AI114131NIAID NIH HHS F32 AI118160NIAID NIH HHS F32AI118160NIAID NIH HHS P01 AI083214NIAID NIH HHS P01AI083214NIAID NIH HHS R01 AI099144NIAID NIH HHS R01AI099144NIAID NIH HHS T32 AI007061NIAID NIH HHS U19 AI109764NIAID NIH HHS U19AI109764NIAID NIH HHS U54 AI057159NIAID NIH HHS U54AI057159
6 · The paper itself

Abstract

The majority of bacterial proteins are dispensable for growth in the laboratory but nevertheless have important physiological roles. There are no systematic approaches to identify cell-permeable small-molecule inhibitors of these proteins. We demonstrate a strategy to identify such inhibitors that exploits synthetic lethal relationships both for small-molecule discovery and for target identification. Applying this strategy in Staphylococcus aureus, we have identified a compound that inhibits DltB, a component of the teichoic acid D-alanylation machinery that has been implicated in virulence. This D-alanylation inhibitor sensitizes S. aureus to aminoglycosides and cationic peptides and is lethal in combination with a wall teichoic acid inhibitor. We conclude that DltB is a druggable target in the D-alanylation pathway. More broadly, the work described demonstrates a systematic method to identify biologically active inhibitors of major bacterial processes that can be adapted to numerous organisms.

Indexed as

AminoglycosidesAmsacrineAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacterial ProteinsCell WallDrug Evaluation, PreclinicalHigh-Throughput Screening AssaysMembrane Transport ProteinsMicrobial Sensitivity TestsMutationSmall Molecule LibrariesStaphylococcus aureusTeichoic AcidsAminoglycosidesAmsacrineAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacterial ProteinsDltB protein, StaphylococcusMembrane Transport ProteinsSmall Molecule LibrariesTeichoic Acids

Identifiers

PMID26619249
PMCPMC4684722
OpenAlexW2234826186

What OpenQuestion holds

Textmetadata
LicenceTDM
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.