PXD052070

PXD052070 is an original dataset announced via ProteomeXchange.

Title	Acarbose Primarily Targets Intracellular GH97 Enzymes in Bacteroides to Impair Their Growth
Description	The type 2 diabetes drug acarbose inhibits starch breakdown into glucose by host gluco(amylases) in the upper gastrointestinal tract. Acarbose is poorly absorbed by host tissue and transits to the large intestine with undigested starch. Numerous gut species in the Bacteroides genus break down starch but decrease in relative abundance in acarbose treated individuals. To mechanistically explain this observation, we used two model Bacteroides, Bacteroides ovatus (Bo) and Bacteroides thetaiotaomicron (Bt). Bt growth is severely impaired by acarbose whereas Bo growth is not. The Bacteroides use a starch utilization system (Sus) to grow on starch. We hypothesized that Bo and Bt Sus enzymes are differentially inhibited by acarbose and identified the periplasmic enzymes BoGH97CSus and SusB as the primer acarbose phenotype drivers. But, they do not explain the differential growth inhibition in Bo and Bt. Instead, acarbose affects starch processing at multiple points by competing for transport through the Sus beta-barrel proteins and binding to the Sus transcriptional regulators. Bo expresses a non-Sus GH97, BoGH97D, when grown in starch with acarbose. The Bt homolog, BtGH97H, is not expressed in the same conditions. Bt, however, does not benefit from overexpressing BoGH97D when exposed to acarbose. Though we predicted that acarbose exerts its effects on Bacteroides via enzyme inhibition, the drug interferes with multiple components of Sus to likely decrease bacterial fitness in the human gut. This work informs how acarbose exerts its beneficial effects on the microbiota and can be used to predict microbiota responsiveness to the drug.
HostingRepository	PRIDE
AnnounceDate	2024-10-18
AnnouncementXML	Submission_2024-10-18_08:46:27.065.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicole Koropatkin
SpeciesList	scientific name: Bacteroides ovatus ATCC 8483; NCBI TaxID: 411476;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-07 03:45:57	ID requested
⏵ 1	2024-10-18 08:46:27	announced

Dataset with its publication pending

submitter keyword: acarbose

alpha-amylase

glucosidase

glycoside hydrolase family 13

glycoside hydrolase family 97

Bacteroidota

Nicole Koropatkin
contact affiliation	Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA
contact email	nkoropat@umich.edu
lab head
Nicole Koropatkin
contact affiliation	University of Michigan Medical School
contact email	nkoropat@umich.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052070
     1. Label: PRIDE project
     2. Name: Acarbose Primarily Targets Intracellular GH97 Enzymes in Bacteroides to Impair Their Growth