A Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

ABSTRACT Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibio...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Schuyler A. Chambers, Rebecca E. Moore, Kelly M. Craft, Harrison C. Thomas, Rishub Das, Shannon D. Manning, Simona G. Codreanu, Stacy D. Sherrod, David M. Aronoff, John A. McLean, Jennifer A. Gaddy, Steven D. Townsend
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	group B Streptococcus human milk oligosaccharides resistance adjuvants antifolate drugs Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bed98e0db5e049edbda650b23600e004
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bed98e0db5e049edbda650b23600e004
record_format	dspace
spelling	oai:doaj.org-article:bed98e0db5e049edbda650b23600e0042021-11-15T15:57:02ZA Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim10.1128/mBio.00076-202150-7511https://doaj.org/article/bed98e0db5e049edbda650b23600e0042020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00076-20https://doaj.org/toc/2150-7511ABSTRACT Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs’ mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs. IMPORTANCE Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.Schuyler A. ChambersRebecca E. MooreKelly M. CraftHarrison C. ThomasRishub DasShannon D. ManningSimona G. CodreanuStacy D. SherrodDavid M. AronoffJohn A. McLeanJennifer A. GaddySteven D. TownsendAmerican Society for Microbiologyarticlegroup B Streptococcushuman milk oligosaccharidesresistanceadjuvantsantifolate drugsMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	group B Streptococcus human milk oligosaccharides resistance adjuvants antifolate drugs Microbiology QR1-502
spellingShingle	group B Streptococcus human milk oligosaccharides resistance adjuvants antifolate drugs Microbiology QR1-502 Schuyler A. Chambers Rebecca E. Moore Kelly M. Craft Harrison C. Thomas Rishub Das Shannon D. Manning Simona G. Codreanu Stacy D. Sherrod David M. Aronoff John A. McLean Jennifer A. Gaddy Steven D. Townsend A Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
description	ABSTRACT Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs’ mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs. IMPORTANCE Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.
format	article
author	Schuyler A. Chambers Rebecca E. Moore Kelly M. Craft Harrison C. Thomas Rishub Das Shannon D. Manning Simona G. Codreanu Stacy D. Sherrod David M. Aronoff John A. McLean Jennifer A. Gaddy Steven D. Townsend
author_facet	Schuyler A. Chambers Rebecca E. Moore Kelly M. Craft Harrison C. Thomas Rishub Das Shannon D. Manning Simona G. Codreanu Stacy D. Sherrod David M. Aronoff John A. McLean Jennifer A. Gaddy Steven D. Townsend
author_sort	Schuyler A. Chambers
title	A Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
title_short	A Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
title_full	A Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
title_fullStr	A Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
title_full_unstemmed	A Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim
title_sort	solution to antifolate resistance in group b <italic toggle="yes">streptococcus</italic>: untargeted metabolomics identifies human milk oligosaccharide-induced perturbations that result in potentiation of trimethoprim
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/bed98e0db5e049edbda650b23600e004
work_keys_str_mv	AT schuylerachambers asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT rebeccaemoore asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT kellymcraft asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT harrisoncthomas asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT rishubdas asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT shannondmanning asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT simonagcodreanu asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT stacydsherrod asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT davidmaronoff asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT johnamclean asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT jenniferagaddy asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT stevendtownsend asolutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT schuylerachambers solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT rebeccaemoore solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT kellymcraft solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT harrisoncthomas solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT rishubdas solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT shannondmanning solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT simonagcodreanu solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT stacydsherrod solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT davidmaronoff solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT johnamclean solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT jenniferagaddy solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim AT stevendtownsend solutiontoantifolateresistanceingroupbitalictoggleyesstreptococcusitalicuntargetedmetabolomicsidentifieshumanmilkoligosaccharideinducedperturbationsthatresultinpotentiationoftrimethoprim
_version_	1718427049201238016

A Solution to Antifolate Resistance in Group B <italic toggle="yes">Streptococcus</italic>: Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

Ejemplares similares