Dataset Information

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

ABSTRACT: 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)-?-D-Ribf-(1?4)-?-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.

SUBMITTER: Hassan AA

PROVIDER: S-EPMC5462993 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hassan A A AA Maldonado Rita F RF Dos Santos Sandra C SC Di Lorenzo Flaviana F Silipo Alba A Coutinho Carla P CP Cooper Vaughn S VS Molinaro Antonio A Valvano Miguel A MA Sá-Correia Isabel I

Frontiers in microbiology 20170608

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 i ...[more]

PMID: 28642745

Similar Datasets

Project description:During cystic fibrosis (CF) chronic lung infections, bacteria of the Burkholderia cepacia complex (Bcc) are exposed for several years to a stressful and changing environment. These environmental challenges results in genetic changes of the initial infecting strain with the consequent diversification of genotypes and phenotypes. The exploitation of functional and comparative genomic approaches has suggested that such diversification is associated with massive metabolic remodeling but these alterations are poorly understood. In the present work, we have explored a high resolution 1H-NMR-based metabolomic approach coupled to multivariate analysis to compare the endometabolome of three B. cenocepacia clonal variants retrieved from a CF patient from the onset of infection (IST439) until death with cepacia syndrome after 3.5 years (IST4113 and IST4134), to complement former proteomic and transcriptomic analyses. A fourth clonal variant (IST4129) retrieved from the same CF patient when the clinical condition worsened during the last months of life, was also examined since it was found to lack the third replicon. The metabolomic profiles obtained, based on the complete 1H-NMR spectra, highlight the separation of the four clonal variants examined, the most distinct profile corresponding to IST4129. Results indicate a variable content of several amino acids in the different isolates examined and suggest that glycolysis and the glyoxylate shunt are favored in late variants. Moreover, the concentration of two metabolites with demonstrated cellular protective functions against stress, glycine-betaine and trehalose, is different in the different isolates examined. However, no clear correlation could be established between their content and stress tolerance. For example, IST4113, previously found to be the most resistant variant to antimicrobials of different classes, exhibits low levels of trehalose and glycine-betaine but the highest resistance to heat and oxidative stress. Also, IST4129, with a high level of glycine-betaine but lacking the third replicon, previously associated with stress resistance and virulence, exhibits the highest susceptibility to all the stresses tested. Taken together, results from this study provide insights into the metabolic diversification of B. cenocepacia clonal variants during long-term infection of the CF airways.

Project description:Burkholderia cenocepacia causes severe pulmonary infections in cystic fibrosis (CF) patients. Since the bacterium is virtually untreatable by antibiotics, chronic infections persist for years and might develop into fatal septic pneumonia (cepacia syndrome, CS). To devise new strategies to combat chronic B. cenocepacia infections, it is essential to obtain comprehensive knowledge about their pathogenesis. We conducted a comparative genomic analysis of 32 Czech isolates of epidemic clone B. cenocepacia ST32 isolated from various stages of chronic infection in 8 CF patients. High numbers of large-scale deletions were found to occur during chronic infection, affecting preferentially genomic islands and nonessential replicons. Recombination between insertion sequences (IS) was inferred as the mechanism behind deletion formation; the most numerous IS group was specific for the ST32 clone and has undergone transposition burst since its divergence. Genes functionally related to transition metal metabolism were identified as hotspots for deletions and IS insertions. This functional category was also represented among genes where nonsynonymous point mutations and indels occurred parallelly among patients. Another category exhibiting parallel mutations was oxidative stress protection; mutations in catalase KatG resulted in impaired detoxification of hydrogen peroxide. Deep sequencing revealed substantial polymorphism in genes of both categories within the sputum B. cenocepacia ST32 populations, indicating extensive adaptive evolution. Neither oxidative stress response nor transition metal metabolism genes were previously reported to undergo parallel evolution during chronic CF infection. Mutations in katG and copper metabolism genes were overrepresented in patients where chronic infection developed into CS. Among professional phagocytes, macrophages use both hydrogen peroxide and copper for their bactericidal activity; our results thus tentatively point to macrophages as suspects in pathogenesis towards the fatal CS.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets