PXD075197-1

PXD075197 is an original dataset announced via ProteomeXchange.

Title	Salmonella-derived heme inhibits macrophage phagocytosis and promotes infection in mice
Description	Bacterial pathogens such as Salmonella enterica serovar Typhimurium can resist phagocytosis by macrophages. Here we explored the role of bacterial heme biosynthesis in phagocytosis resistance. Using transposon sequencing (Tn-seq) during Salmonella infection of macrophages, we identify a methyltransferase, SirM, that indirectly inhibits phagocytosis of bacteria. Mechanistically, sirM is activated upon interaction with macrophages and methylates HemL, a key enzyme in heme biosynthesis, resulting in upregulation of heme synthesis by Salmonella. Salmonella-derived heme inhibits Cdc42 activation in a Toll-like receptor 4 (TLR4)-dependent manner to inhibit phagocytosis. Moreover, sirM promotes macrophage death by increasing heme synthesis. Experiments in mouse models show that sirM is required for virulence and confers a competitive advantage over intestinal commensal bacteria during infection. We also found that sirM is distributed among enteric pathogens. Collectively, our findings show that bacterial heme promotes evasion of phagocyte responses and pathogenesis to confer an advantage in the host.
HostingRepository	PRIDE
AnnounceDate	2026-04-07
AnnouncementXML	Submission_2026-04-07_06:45:26.378.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zuoqiang Wang
SpeciesList	scientific name: Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720); NCBI TaxID: NEWT:99287;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-04 02:44:28	ID requested
⏵ 1	2026-04-07 06:45:26	announced

Dataset with its publication pending

submitter keyword: macrophage

phagocytosis

methyltransferase

heme

TLR4

Yu-Feng Yao
contact affiliation	Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine.
contact email	yfyao@sjtu.edu.cn
lab head
Zuoqiang Wang
contact affiliation	Shanghai Jiao Tong University School of Medicine
contact email	wallylovemolly@126.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD075197

PRIDE project URI

• PRIDE
  1. PXD075197
     1. Label: PRIDE project
     2. Name: Salmonella-derived heme inhibits macrophage phagocytosis and promotes infection in mice