Evidence map›Paper›PMID 41833947›Full record

ArticleNature communications2026

Candesartan cilexetil disrupts methicillin-resistant Staphylococcus aureus membrane and potentiates gentamicin and polymyxin B activity.

Nagendran Tharmalingam, Robert Wilson Kovacs, Suelen Scarpa de Mello, Philip Rupert Baldwin, Harikrishna Sekar Jayanthan, Kulandaisamy Arulsamy, Rajmohan Rajmuthiah, Fernanda Cristina Possamai Rossatto, Katherine E Manz, Joseph A DeGiorgis and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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

16 authors.

Nagendran TharmalingamDepartment of Medicine, Houston Methodist Research Institute, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6107-3754
Robert Wilson Kovacs *Department of Chemistry, University of Miami, Coral Gables, FL, USA.
Suelen Scarpa de Mello *Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6389-6041
Philip Rupert Baldwin *Biochemistry and Molecular Pharmacology Baylor College of Medicine, Houston, TX, USA.
Harikrishna Sekar JayanthanVanderblit University, Nashville, TN, USA.
Kulandaisamy ArulsamyBoston Children's Hospital, Boston, MA, USA.
Rajmohan RajmuthiahDepartment of Infectious disease, Division of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
Fernanda Cristina Possamai RossattoDepartment of Infectious disease, Division of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
Katherine E ManzSchool of Engineering, Brown University, Providence, RI, USA.
Joseph A DeGiorgisProvidence College, Providence, RI, USA.
Orlando AcevedoDepartment of Chemistry, University of Miami, Coral Gables, FL, USA.ORCID http://orcid.org/0000-0002-6110-3930
Michael S GilmoreHarvard Medical School, Boston, MA, USA.
Steven J LudtkeBiochemistry and Molecular Pharmacology Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1903-1574
Kurt D PennellSchool of Engineering, Brown University, Providence, RI, USA.ORCID http://orcid.org/0000-0002-5788-6397
Frederick M AusubelHarvard Medical School, Boston, MA, USA.
Eleftherios MylonakisDepartment of Medicine, Houston Methodist Research Institute, Houston, TX, USA. emylonakis@houstonmethodist.org.ORCID http://orcid.org/0000-0002-4624-0777

Funding

Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI David C Hooper · 2009 to 2026
$39.4M
NIAID NIH HHS P01 AI083214
6 · The paper itself

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of bacterial infections, but treatment options are limited due to MRSA multi-drug resistance. The anti-hypertensive drug Candesartan cilexetil (CC) exhibits potent anti-MRSA activity. It permeabilizes the membrane of MRSA cells and potentiates the activity of aminoglycoside antibiotics. Here, we used a variety of methods to elucidate the mechanism by which CC disrupts membrane homeostasis. We show that CC binds to bilayer lipid molecules, decreases membrane fluidity, down-regulates cell membrane and cell wall related genes and related metabolites, and decreases C20 fatty acids (C20:0). Decreasing C20:0 fatty acids confers CC- resistance, which can be reversed by C20:0 supplementation. Structural activity relationship analysis shows that the tetrazole ring and ester carbonic acid of CC are critical for antibacterial activity. Finally, CC reduces MRSA-MW2 replication in a murine MRSA abscess model, supporting a potential role of CC as a lead antimicrobial compound/potentiator against MRSA.

Indexed as

Anti-Bacterial AgentsBenzimidazolesBiphenyl CompoundsCell MembraneGentamicinsMethicillin-Resistant Staphylococcus aureusTetrazolesAbscessAnimalsCell WallDrug SynergismFatty AcidsMembrane FluidityMiceMicrobial Sensitivity TestsStaphylococcal InfectionsAnti-Bacterial AgentsBenzimidazolesBiphenyl Compoundscandesartan cilexetilFatty AcidsGentamicinsTetrazoles

Identifiers

PMID41833947
PMCPMC13136397

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.