PXD075029-1

PXD075029 is an original dataset announced via ProteomeXchange.

Title	A synthetic rationally designed antimicrobial peptide attenuates Salmonella invasion by suppressing SPI-1 and motility
Description	Antimicrobial peptides (AMPs) are increasingly recognized for activities beyond bacterial killing, including modulation of virulence at sub-inhibitory concentrations. Here we examined a panel of synthetic α-helical AMPs originally designed against non-pathogenic Escherichia coli for activity against Salmonella enterica serovar Typhimurium. Under physiological salt conditions, these peptides exhibited antimicrobial activity against laboratory and multidrug-resistant Salmonella isolates. Using a prgH::gfp reporter, we found that several of the peptides reduced expression of the Salmonella pathogenicity island 1 (SPI-1) type III secretion system at concentrations below those required for growth inhibition. This effect occurred under conditions that did not affect bacterial growth, viability, or gross morphology, as confirmed by MIC determination, time-kill assays across growth phases, and electron microscopy. One of these peptides, the Leu/Ile-rich L1L, attenuated SPI-1 expression sufficiently to reduce epithelial cell invasion in gentamicin protection assays. Whereas the corresponding D-enantiomer and the Trp/Arg-rich L24 peptide showed less activity, indicating that stereochemistry and sequence composition critically influence virulence modulation independently of antibacterial potency. Direct comparison with polymyxin B demonstrated that L1L suppressed SPI-1 expression at a lower fraction of its inhibitory concentration, highlighting a greater separation between virulence attenuation and growth inhibition. Proteomic analysis revealed that L1L exposure induces envelope remodeling and antimicrobial peptide resistance pathways while repressing SPI-1 regulators and effectors, consistent with a regulatory shift from invasion toward stress adaptation. Together, these findings demonstrate that synthetic AMPs can exert potent, stereochemically specific anti-virulence effects against Salmonella at sub-inhibitory concentrations and underscore the importance of incorporating virulence-associated endpoints and benchmark comparisons into future AMP design and evaluation strategies.
HostingRepository	PRIDE
AnnounceDate	2026-08-13
AnnouncementXML	Submission_2026-08-13_04:06:55.895.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yixiang Zhang
SpeciesList	scientific name: Salmonella enterica subsp. enterica serovar Typhimurium str. SL1344; NCBI TaxID: NEWT:216597;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-27 22:19:26	ID requested
⏵ 1	2026-08-13 04:06:56	announced

10.1128/SPECTRUM.01215-26;

submitter keyword: Anti-virulence, antimicrobial peptide, Salmonella enterica serovar Typhimurium, type III secretion system, virulence regulation

Olivia Steele-Mortimer
contact affiliation	Chief, Salmonella-Host Cells Interactions Section Deputy-Chief, Laboratory of Bacteriology National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health Rocky Mountain Laboratories 6212 406-363 9292
contact email	OMortimer@niaid.nih.gov
lab head
Yixiang Zhang
contact affiliation	RML/NIAID/NIH
contact email	alexzhangyx@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD075029
     1. Label: PRIDE project
     2. Name: A synthetic rationally designed antimicrobial peptide attenuates Salmonella invasion by suppressing SPI-1 and motility