Evidence map›Paper›PMID 42234660›Full record

ArticlePloS one2026

Staphylococcus aureus agr-type vs genetic background: molecular signatures determining differential metabolism and virulence potential.

Mariane Pivard, Julian Bär, Tomas Demeter, Srikanth Mairpady Shambat, Annelies S Zinkernagel

Abstract read
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

5 authors.

Mariane PivardDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland‌‌.ORCID https://orcid.org/0000-0002-8357-1380
Julian BärDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland‌‌.ORCID https://orcid.org/0000-0003-1929-0338
Tomas DemeterDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland‌‌.
Srikanth Mairpady ShambatDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland‌‌.
Annelies S ZinkernagelDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland‌‌.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In Staphylococcus aureus, the quorum‑sensing accessory gene regulator (agr) system is the major virulence regulator. The four agr‑types (I-IV) have been associated with distinct infection outcomes, but their direct contribution to virulence regulation and metabolism has remained unresolved due to tight linkage between agr‑type and genetic background. To disentangle agr‑type‑specific effects, we used congenic Newman strains in which the native agr-locus has been replaced with each of the four agr-types, alongside a [Formula: see text]agr mutant. We performed RNA‑sequencing during early exponential (1h30), late exponential (6h), and stationary (12h) growth phases. Despite similar growth kinetics, agr‑types displayed distinct activation profiles based on agrA and RNAIII expressions. Agr-I and agr-IV showed early, strong expressions, agr-II displayed intermediate expressions and agr-III initiated weak expressions only in stationary phase. This agr‑type‑dependent activation timing was the dominant driver of global transcriptional changes. Early activation in agr‑I and agr‑IV induced robust expression of phenol‑soluble modulins, capsule biosynthesis genes, and pore‑forming toxins, whereas agr‑II and agr‑III expressed delayed or alternative virulence pathways, including upregulation of superantigen‑like genes. Among all types, agr‑IV exhibited the broadest transcriptional response, encompassing both virulence and metabolic pathways, including differential regulation of nucleotide and fructose metabolisms. Pairwise differential expression, over‑representation analysis, and gene‑set enrichment consistently revealed agr‑type‑specific virulence and metabolic programs. Agr‑III, which activated latest and weakest, showed limited transcriptional change until stationary phase, whereas agr‑I, agr‑II, and agr‑IV displayed progressively broader virulence and metabolic remodeling. Together, these findings demonstrate that agr‑type determines virulence and metabolic gene expression profiles primarily by dictating the timing and magnitude of agr-activation, even within an identical genetic background and growth environment. This work provides a systematic framework for understanding agr‑type‑specific regulatory strategies and their potential roles in S. aureus pathogenesis.

Indexed as

Bacterial ProteinsStaphylococcus aureusTrans-ActivatorsGene Expression ProfilingGene Expression Regulation, BacterialQuorum SensingVirulenceAgr protein, Staphylococcus aureusBacterial ProteinsTrans-Activators

Identifiers

PMID42234660
PMCPMC13232812

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.