Property space mapping of Pseudomonas aeruginosa permeability to small molecules.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 05 2022
17 05 2022
Historique:
received:
10
02
2022
accepted:
10
05
2022
entrez:
17
5
2022
pubmed:
18
5
2022
medline:
20
5
2022
Statut:
epublish
Résumé
Two membrane cell envelopes act as selective permeability barriers in Gram-negative bacteria, protecting cells against antibiotics and other small molecules. Significant efforts are being directed toward understanding how small molecules permeate these barriers. In this study, we developed an approach to analyze the permeation of compounds into Gram-negative bacteria and applied it to Pseudomonas aeruginosa, an important human pathogen notorious for resistance to multiple antibiotics. The approach uses mass spectrometric measurements of accumulation of a library of structurally diverse compounds in four isogenic strains of P. aeruginosa with varied permeability barriers. We further developed a machine learning algorithm that generates a deterministic classification model with minimal synonymity between the descriptors. This model predicted good permeators into P. aeruginosa with an accuracy of 89% and precision above 58%. The good permeators are broadly distributed in the property space and can be mapped to six distinct regions representing diverse chemical scaffolds. We posit that this approach can be used for more detailed mapping of the property space and for rational design of compounds with high Gram-negative permeability.
Identifiants
pubmed: 35581346
doi: 10.1038/s41598-022-12376-1
pii: 10.1038/s41598-022-12376-1
pmc: PMC9114115
doi:
Substances chimiques
Anti-Bacterial Agents
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
8220Subventions
Organisme : NIH HHS
ID : AI136795
Pays : United States
Organisme : NIH HHS
ID : AI052293
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132836
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136795
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI052293
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
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