PXD063111-1

PXD063111 is an original dataset announced via ProteomeXchange.

Title	Carbohydrates and the oxidative branch of the pentose phosphate pathway modify Bacteroides thetaiotaomicron phage resistance by phase variable S-layers
Description	The human gut microbiota consists of hundreds of bacterial species, some of which persist in the presence of lytic phage that infect them. Bacteroides employ numerous phase-variable strategies to survive in the presence of phage, including capsular polysaccharides (CPS) and S-layer lipoproteins. We previously reported that a Bacteroides thetaiotaomicron strain lacking CPS exhibits almost complete resistance to multiple phages when forced to express the S-layer protein BT1927. However, this strain was only resistant after certain growth conditions, suggesting nutritional variables alter infection and resistance. We grew this strain on various simple sugars and polysaccharides finding that some substrates (fructose, glucose) promote strong resistance to a single phage (ARB25) while others like N-acetylgalactosamine (GalNAc) and mucin O-glycans increase susceptibility. Mixing fructose and GalNAc indicates the effects of GalNAc are dominant. Despite increasing ARB25 susceptibility, GalNAc did not reduce BT1927 transcript or protein levels. Instead, GalNAc reduced the amount of BT1927 displayed on the cell surface and increased outer membrane vesiculation. Mutants in any of the 3 steps of the oxidative branch of the pentose phosphate pathway—grown in fructose—behaved similarly to wild-type cells grown in GalNAc, illuminating this pathway in regulation of sugar-mediated phage-resistance. Despite promoting strong resistance, cells grown in glucose/fructose sometimes displayed sub-populations that appeared to completely lack surface BT1927, suggesting another checkpoint exists to control whether this phage defense is deployed. Finally, we show the mucin sugar GalNAc increases susceptibility to several other phage, which has implications for B. thetaiotaiomicron persistence in niches like the mucus layer.
HostingRepository	PRIDE
AnnounceDate	2025-08-22
AnnouncementXML	Submission_2025-08-22_06:44:14.360.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jaime Fuentes
SpeciesList	scientific name: Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482); NCBI TaxID: 226186;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-18 08:25:06	ID requested
⏵ 1	2025-08-22 06:44:15	announced

Fuentes JJ, Singh S, Pudlo NA, Heaver SL, Ley RE, Martens EC, phage resistance by phase variable S-layers. bioRxiv, ():(2025) [pubmed]

10.1101/2025.05.01.651756;

submitter keyword: phage, bacteroides,surface layer

Eric C
contact affiliation	Department of Microbiology and Immunology, University of Michigan, 1150 W Medical Center Dr, 1526 MSRB1, Ann Arbor, MI, 48109.
contact email	emartens@umich.edu
lab head
Jaime Fuentes
contact affiliation	University of Michigan
contact email	jfuen@umich.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063111
     1. Label: PRIDE project
     2. Name: Carbohydrates and the oxidative branch of the pentose phosphate pathway modify Bacteroides thetaiotaomicron phage resistance by phase variable S-layers