Evidence map›Paper›PMID 40447280›Full record

SynthesisThe Journal of infectious diseases2025

Genome-Scale Meta-analysis of Host Responses to Staphylococcus aureus Identifies Pathways for Host-Directed Therapeutic Targeting.

Clark D Russell, Seraphima Goeldner-Thompson, Emilie Smith, Jonathan E Millar, Bo Wang, Nicholas Parkinson, Sara Clohisey Hendry, Maaike Swets, J Ross Fitzgerald, J Kenneth Baillie and 1 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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.

Clark D RussellUniversity of Edinburgh Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh, United Kingdom.ORCID 0000-0002-9873-8243
Seraphima Goeldner-ThompsonUniversity of Edinburgh Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh, United Kingdom.
Emilie SmithUniversity of Edinburgh Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh, United Kingdom.
Jonathan E MillarBaillie-Gifford Pandemic Science Hub, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom.
Bo WangBaillie-Gifford Pandemic Science Hub, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-1580-797X
Nicholas ParkinsonRoslin Institute, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0001-6336-5654
Sara Clohisey HendryBaillie-Gifford Pandemic Science Hub, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0001-7489-9846
Maaike SwetsRoslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
J Ross FitzgeraldRoslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
J Kenneth BaillieUniversity of Edinburgh Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh, United Kingdom.ORCID 0000-0001-5258-793X
David H DockrellUniversity of Edinburgh Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh, United Kingdom.ORCID 0000-0002-2718-4861

Funding

Academy of Medical Sciences SGL032\1020Edinburgh Clinical Academic Track/Wellcome Trust PhD Training Fellowship 214178/Z/18/Zthe SHIELD consortium "Optimising Innate Host Defence to Combat Antimicrobial Resistance" MR/NO2995X/1UK Research and Innovation/Medical Research Council (MRC) MR/Y013131/1)Wellcome TrustWellcome Trust 211496/Z/18/Z
6 · The paper itself

Abstract

backgroundStaphylococcus aureus infections are frequently complicated by metastatic foci, recurrence, and death. Antimicrobial resistance and intracellular bacterial persistence limit the effectiveness of conventional antimicrobials. Host-directed therapies could improve outcomes, but the interpretive complexity of pathogen-host interactions impedes identification of critical responses suitable for therapeutic targeting. To address this, we performed a meta-analysis of genome-scale studies aiming to prioritize host responses to S aureus.

methodsLists of genes associated with host responses to S aureus were retrieved from systematically identified genome-scale studies, then integrated using the meta-analysis by information content (MAIC) algorithm. This generated a single aggregated gene list, ranked based on the cumulative evidence supporting each gene.

resultsMAIC prioritized 3867 host genes. Myeloid cell immune responses were enriched with specific hubs including TLR2, IL-17, IFN-γ, and IL-1β. Noncanonical effector pathways were also enriched: autophagy (specific factors including mTOR and LAMP2), apoptosis (including BAD and BID), ferroptosis and iron metabolism (TFRC ranked 8/3876), and proteasomal antimicrobial responses (including PSME3 and the novel antimicrobial peptide PPP1CB). Prioritized genes were associated with genome-wide association study traits related to platelet count. In a cohort of patients with S aureus bacteremia, platelet count was differentially associated with clinical outcomes. Targets with immediate therapeutic relevance included S aureus/fibrin/platelet microthrombus formation (VWF, GP11b), S aureus-induced platelet loss (ASGR2), autophagy (mTOR), BID-mediated apoptosis, and intracellular bacterial killing (IFN-γ).

conclusionsThis in silico analysis identifies cytokine hubs associated with the response to S aureus infection and prioritizes additional host responses including apoptosis, autophagy, iron metabolism, and thrombosis as therapeutic targets.

Indexed as

Host-Pathogen InteractionsStaphylococcal InfectionsStaphylococcus aureusGenome-Wide Association StudyHumanshost-directed therapyinnate immunityphagocyteplateletStaphylococcus aureus

Identifiers

PMID40447280
PMCPMC12349957

What Socratic holds

Textmetadata
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 Socratic graph.