Genetic Basis for Activity Differences Between Vancomycin and Glycolipid Derivatives of Vancomycin

U S Eggert; N Ruiz; B V Falcone; A A Branstrom; R C Goldman; T J Silhavy; D Kahne; Ulrike Eggert

doi:10.1126/science.1063611

Genetic Basis for Activity Differences Between Vancomycin and Glycolipid Derivatives of Vancomycin

U S Eggert, N Ruiz, B V Falcone, A A Branstrom, R C Goldman, T J Silhavy, D Kahne, Ulrike Eggert

Princeton University

Research output: Contribution to journal › Article › peer-review

123 Citations (Scopus)

Abstract

Small molecules that affect specific protein functions can be valuable tools for dissecting complex cellular processes. Peptidoglycan synthesis and degradation is a process in bacteria that involves multiple enzymes under strict temporal and spatial regulation. We used a set of small molecules that inhibit the transglycosylation step of peptidoglycan synthesis to discover genes that help to regulate this process. We identified a gene responsible for the susceptibility of Escherichia coli cells to killing by glycolipid derivatives of vancomycin, thus establishing a genetic basis for activity differences between these compounds and vancomycin.

Original language	English
Pages (from-to)	361-364
Number of pages	4
Journal	Science
Volume	294
Issue number	5541
DOIs	https://doi.org/10.1126/science.1063611
Publication status	Published - 12 Oct 2001

Keywords

Anti-Bacterial Agents
Bacterial Proteins
Drug Resistance, Microbial
Drug Resistance, Multiple
Enzyme Inhibitors
Escherichia coli
Genes, Bacterial
Genetic Complementation Test
Glycosylation
Hexosyltransferases
Lipoproteins
Microbial Sensitivity Tests
Mutation
N-Acetylmuramoyl-L-alanine Amidase
Oligosaccharides
Peptidoglycan
Peptidoglycan Glycosyltransferase
Phenotype
Vancomycin
Vancomycin Resistance

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title = "Genetic Basis for Activity Differences Between Vancomycin and Glycolipid Derivatives of Vancomycin",

abstract = "Small molecules that affect specific protein functions can be valuable tools for dissecting complex cellular processes. Peptidoglycan synthesis and degradation is a process in bacteria that involves multiple enzymes under strict temporal and spatial regulation. We used a set of small molecules that inhibit the transglycosylation step of peptidoglycan synthesis to discover genes that help to regulate this process. We identified a gene responsible for the susceptibility of Escherichia coli cells to killing by glycolipid derivatives of vancomycin, thus establishing a genetic basis for activity differences between these compounds and vancomycin.",

keywords = "Anti-Bacterial Agents, Bacterial Proteins, Drug Resistance, Microbial, Drug Resistance, Multiple, Enzyme Inhibitors, Escherichia coli, Genes, Bacterial, Genetic Complementation Test, Glycosylation, Hexosyltransferases, Lipoproteins, Microbial Sensitivity Tests, Mutation, N-Acetylmuramoyl-L-alanine Amidase, Oligosaccharides, Peptidoglycan, Peptidoglycan Glycosyltransferase, Phenotype, Vancomycin, Vancomycin Resistance",

author = "Eggert, {U S} and N Ruiz and Falcone, {B V} and Branstrom, {A A} and Goldman, {R C} and Silhavy, {T J} and D Kahne and Ulrike Eggert",

year = "2001",

month = oct,

day = "12",

doi = "10.1126/science.1063611",

language = "English",

volume = "294",

pages = "361--364",

journal = "Science",

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publisher = "American Association for the Advancement of Science",

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TY - JOUR

T1 - Genetic Basis for Activity Differences Between Vancomycin and Glycolipid Derivatives of Vancomycin

AU - Eggert, U S

AU - Ruiz, N

AU - Falcone, B V

AU - Branstrom, A A

AU - Goldman, R C

AU - Silhavy, T J

AU - Kahne, D

AU - Eggert, Ulrike

PY - 2001/10/12

Y1 - 2001/10/12

N2 - Small molecules that affect specific protein functions can be valuable tools for dissecting complex cellular processes. Peptidoglycan synthesis and degradation is a process in bacteria that involves multiple enzymes under strict temporal and spatial regulation. We used a set of small molecules that inhibit the transglycosylation step of peptidoglycan synthesis to discover genes that help to regulate this process. We identified a gene responsible for the susceptibility of Escherichia coli cells to killing by glycolipid derivatives of vancomycin, thus establishing a genetic basis for activity differences between these compounds and vancomycin.

AB - Small molecules that affect specific protein functions can be valuable tools for dissecting complex cellular processes. Peptidoglycan synthesis and degradation is a process in bacteria that involves multiple enzymes under strict temporal and spatial regulation. We used a set of small molecules that inhibit the transglycosylation step of peptidoglycan synthesis to discover genes that help to regulate this process. We identified a gene responsible for the susceptibility of Escherichia coli cells to killing by glycolipid derivatives of vancomycin, thus establishing a genetic basis for activity differences between these compounds and vancomycin.

KW - Anti-Bacterial Agents

KW - Bacterial Proteins

KW - Drug Resistance, Microbial

KW - Drug Resistance, Multiple

KW - Enzyme Inhibitors

KW - Escherichia coli

KW - Genes, Bacterial

KW - Genetic Complementation Test

KW - Glycosylation

KW - Hexosyltransferases

KW - Lipoproteins

KW - Microbial Sensitivity Tests

KW - Mutation

KW - N-Acetylmuramoyl-L-alanine Amidase

KW - Oligosaccharides

KW - Peptidoglycan

KW - Peptidoglycan Glycosyltransferase

KW - Phenotype

KW - Vancomycin

KW - Vancomycin Resistance

U2 - 10.1126/science.1063611

DO - 10.1126/science.1063611

M3 - Article

C2 - 11520949

SN - 0036-8075

VL - 294

SP - 361

EP - 364

JO - Science

JF - Science

IS - 5541

ER -

Genetic Basis for Activity Differences Between Vancomycin and Glycolipid Derivatives of Vancomycin

Abstract

Keywords

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