Structure of O-Antigen and Hybrid Biosynthetic Locus in Burkholderia cenocepacia Clonal Variants Recovered from a Cystic Fibrosis Patient

Burkholderia cenocepacia is an opportunistic pathogen associated with chronic lung infections and increased risk of death in patients with cystic fibrosis (CF). In this work, we investigated the lipopolysaccharide (LPS) of clinical variants of B. cenocepacia that were collected from a CF patient ove...

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Main Authors: A.A. Hassan, Rita F. Maldonado, Sandra C. dos Santos, Flaviana Di Lorenzo, Alba Silipo, Carla P. Coutinho, Vaughn S. Cooper, Antonio Molinaro, Miguel A. Valvano, Isabel Sá-Correia
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-06-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fmicb.2017.01027/full
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author A.A. Hassan
Rita F. Maldonado
Sandra C. dos Santos
Flaviana Di Lorenzo
Alba Silipo
Carla P. Coutinho
Vaughn S. Cooper
Antonio Molinaro
Miguel A. Valvano
Isabel Sá-Correia
author_facet A.A. Hassan
Rita F. Maldonado
Sandra C. dos Santos
Flaviana Di Lorenzo
Alba Silipo
Carla P. Coutinho
Vaughn S. Cooper
Antonio Molinaro
Miguel A. Valvano
Isabel Sá-Correia
author_sort A.A. Hassan
collection DOAJ
description Burkholderia cenocepacia is an opportunistic pathogen associated with chronic lung infections and increased risk of death in patients with cystic fibrosis (CF). In this work, we investigated the lipopolysaccharide (LPS) of clinical variants of B. cenocepacia that were collected from a CF patient over a period of 3.5 years, from the onset of infection until death by necrotizing pneumonia (cepacia syndrome). We report the chemical structure of the LPS molecule of various sequential isolates and the identification of a novel hybrid O-antigen (OAg) biosynthetic cluster. The OAg repeating unit of the LPS from IST439, the initial isolate, is a [→2)-β-D-Ribf-(1→4)-α-D-GalpNAc-(1→] disaccharide, which was not previously described in B. cenocepacia. The IST439 OAg biosynthetic gene cluster contains 7 of 23 genes that are closely homologous to genes found in B. multivorans, another member of the Burkholderia cepacia complex. None of the subsequent isolates expressed OAg. Genomic sequencing of these isolates enabled the identification of mutations within the OAg cluster, but none of these mutations could be associated with the loss of OAg. This study provides support to the notion that OAg LPS modifications are an important factor in the adaptation of B. cenocepacia to chronic infection and that the heterogeneity of OAgs relates to variation within the OAg gene cluster, indicating that the gene cluster might have been assembled through multiple horizontal transmission events.
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spelling doaj.art-a94cf619ff1445c79a25e38ca2a421312022-12-22T00:49:16ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-06-01810.3389/fmicb.2017.01027268061Structure of O-Antigen and Hybrid Biosynthetic Locus in Burkholderia cenocepacia Clonal Variants Recovered from a Cystic Fibrosis PatientA.A. Hassan0Rita F. Maldonado1Sandra C. dos Santos2Flaviana Di Lorenzo3Alba Silipo4Carla P. Coutinho5Vaughn S. Cooper6Antonio Molinaro7Miguel A. Valvano8Isabel Sá-Correia9Department of Bioengineering, Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de LisboaLisboa, PortugalDepartment of Bioengineering, Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de LisboaLisboa, PortugalDepartment of Bioengineering, Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de LisboaLisboa, PortugalDepartment of Chemical Sciences, University of Napoli Federico II Complesso Universitário Monte SantangeloNapoli, ItalyDepartment of Chemical Sciences, University of Napoli Federico II Complesso Universitário Monte SantangeloNapoli, ItalyDepartment of Bioengineering, Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de LisboaLisboa, PortugalDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, PittsburghPA, United StatesDepartment of Chemical Sciences, University of Napoli Federico II Complesso Universitário Monte SantangeloNapoli, ItalyThe Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University BelfastBelfast, United KingdomDepartment of Bioengineering, Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de LisboaLisboa, PortugalBurkholderia cenocepacia is an opportunistic pathogen associated with chronic lung infections and increased risk of death in patients with cystic fibrosis (CF). In this work, we investigated the lipopolysaccharide (LPS) of clinical variants of B. cenocepacia that were collected from a CF patient over a period of 3.5 years, from the onset of infection until death by necrotizing pneumonia (cepacia syndrome). We report the chemical structure of the LPS molecule of various sequential isolates and the identification of a novel hybrid O-antigen (OAg) biosynthetic cluster. The OAg repeating unit of the LPS from IST439, the initial isolate, is a [→2)-β-D-Ribf-(1→4)-α-D-GalpNAc-(1→] disaccharide, which was not previously described in B. cenocepacia. The IST439 OAg biosynthetic gene cluster contains 7 of 23 genes that are closely homologous to genes found in B. multivorans, another member of the Burkholderia cepacia complex. None of the subsequent isolates expressed OAg. Genomic sequencing of these isolates enabled the identification of mutations within the OAg cluster, but none of these mutations could be associated with the loss of OAg. This study provides support to the notion that OAg LPS modifications are an important factor in the adaptation of B. cenocepacia to chronic infection and that the heterogeneity of OAgs relates to variation within the OAg gene cluster, indicating that the gene cluster might have been assembled through multiple horizontal transmission events.http://journal.frontiersin.org/article/10.3389/fmicb.2017.01027/fullBurkholderia cepacia complexcystic fibrosischronic infectionO-antigenlipopolysaccharideclonal variation
spellingShingle A.A. Hassan
Rita F. Maldonado
Sandra C. dos Santos
Flaviana Di Lorenzo
Alba Silipo
Carla P. Coutinho
Vaughn S. Cooper
Antonio Molinaro
Miguel A. Valvano
Isabel Sá-Correia
Structure of O-Antigen and Hybrid Biosynthetic Locus in Burkholderia cenocepacia Clonal Variants Recovered from a Cystic Fibrosis Patient
Frontiers in Microbiology
Burkholderia cepacia complex
cystic fibrosis
chronic infection
O-antigen
lipopolysaccharide
clonal variation
title Structure of O-Antigen and Hybrid Biosynthetic Locus in Burkholderia cenocepacia Clonal Variants Recovered from a Cystic Fibrosis Patient
title_full Structure of O-Antigen and Hybrid Biosynthetic Locus in Burkholderia cenocepacia Clonal Variants Recovered from a Cystic Fibrosis Patient
title_fullStr Structure of O-Antigen and Hybrid Biosynthetic Locus in Burkholderia cenocepacia Clonal Variants Recovered from a Cystic Fibrosis Patient
title_full_unstemmed Structure of O-Antigen and Hybrid Biosynthetic Locus in Burkholderia cenocepacia Clonal Variants Recovered from a Cystic Fibrosis Patient
title_short Structure of O-Antigen and Hybrid Biosynthetic Locus in Burkholderia cenocepacia Clonal Variants Recovered from a Cystic Fibrosis Patient
title_sort structure of o antigen and hybrid biosynthetic locus in burkholderia cenocepacia clonal variants recovered from a cystic fibrosis patient
topic Burkholderia cepacia complex
cystic fibrosis
chronic infection
O-antigen
lipopolysaccharide
clonal variation
url http://journal.frontiersin.org/article/10.3389/fmicb.2017.01027/full
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