PXD076596-1

PXD076596 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of primary human bronchial epithelial cells and extracellular vesicles secreted by polymicrobial culture.
Description	Chronic antibiotic-resistant polymicrobial infections are the leading cause of death in adults with cystic fibrosis (CF). We developed a polymicrobial culture model containing four genera that represents a ‘pulmotype’ detected in ~34% of lung infections in people with CF (pwCF), and accounts for 27% of the variability in lung function. This community, comprised of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica, is grown in synthetic CF media (SCFM2) under anoxic conditions that mimic the environment in mucus plugs in CF. We have shown that Pseudomonas in monoculture communicates with primary human bronchial epithelial cells (pHBEC) by secreting bacterial extracellular vesicles (bEVs) that diffuse through mucus and deliver virulence factors, DNA, and RNA to pHBEC. We report herein that each bacterial genus in the polymicrobial community secretes bEVs containing proteins and RNAs predicted to promote the establishment of chronic infection by enhancing virulence and biofilm formation, and upregulating the stress response and pro-inflammatory pathways in pHBEC. This response is most pronounced in CF pHBEC. Trikafta, a highly effective modulator therapy, does not ameliorate the response or return it to WT levels. Bacterial EVs also inhibited Trikafta-stimulated CFTR Cl- currents by CF pHBEC. These studies provide insight into why Trikafta does not eliminate polymicrobial lung infections and a hyperinflammatory lung environment in pwCF.
HostingRepository	PRIDE
AnnounceDate	2026-04-13
AnnouncementXML	Submission_2026-04-13_07:55:27.554.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Samuel Smukowski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-03 17:29:09	ID requested
⏵ 1	2026-04-13 07:55:28	announced

10.64898/2026.04.09.717493;

submitter keyword: Human bronchial Epithelial cells, Pseudomonas aeruginosa strain PA14, Staphylococcus aureus strain Newman, Streptococcus sanguinis strain SK36, Pseudomonas aeruginosa strain PA01, Prevotella melaninogenica, Extracellular vesicles

Young Ah Goo
contact affiliation	Mass Spectrometry Technology Access Center (MTAC), McDonnell Genome Institute, Washington University, St. Louis
contact email	Ygoo@wustl.edu
lab head
Samuel Smukowski
contact affiliation	Washington University
contact email	smukowski@wustl.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD076596
     1. Label: PRIDE project
     2. Name: Proteomic analysis of primary human bronchial epithelial cells and extracellular vesicles secreted by polymicrobial culture.