Draft genome sequence determination for cystic fibrosis and chronic granulomatous disease Burkholderia multivorans isolates.
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ABSTRACT:
SUBMITTER: Varga JJ
PROVIDER: S-EPMC3486389 | biostudies-literature | 2012 Nov
REPOSITORIES: biostudies-literature
Publications
Draft genome sequence determination for cystic fibrosis and chronic granulomatous disease Burkholderia multivorans isolates.
Varga John J JJ Losada Liliana L Zelazny Adrian M AM Brinkac Lauren L Harkins Derek D Radune Diana D Hostetler Jessica J Sampaio Elizabeth P EP Ronning Catherine M CM Nierman William C WC Greenberg David E DE Holland Steven M SM Goldberg Joanna B JB
Journal of bacteriology 20121101 22
Burkholderia multivorans is a Gram-negative bacterium and a member of the Burkholderia cepacia complex, which is frequently associated with respiratory infections in people with cystic fibrosis (CF) and chronic granulomatous disease (CGD). We are reporting the genome sequences of 4 B. multivorans strains, 2 from CF patients and 2 from CGD patients. ...[more]
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Project description:Burkholderia cepacia complex (Bcc) comprises opportunistic bacteria infecting hosts such as cystic fibrosis (CF) patients. Bcc long-term infection of CF patient airways has been associated with emergence of phenotypic variation. Here we studied two Burkholderia multivorans clonal isolates (D2095 and D2214) displaying different morphotypes from a chronically infected CF patient in order to evaluate traits development during lung infection.
2011-08-22 | GSE28306 | GEO
Project description:Burkholderia cepacia complex (Bcc) comprises opportunistic bacteria infecting hosts such as cystic fibrosis (CF) patients. Bcc long-term infection of CF patient airways has been associated with emergence of phenotypic variation. Here we studied two Burkholderia multivorans clonal isolates (D2095 and D2214) displaying different morphotypes from a chronically infected CF patient in order to evaluate traits development during lung infection. For expression profiling, overnight cultures of the mucoid D2095 and the nonmucoid D2214 isolates grown in SM medium were diluted to an initial OD640 nm of 0.1 into the same medium. Triplicate samples were cultured at 37ºC with 250 r.p.m. agitation for 17 h and RNA extracted from the two bacterial isolates.
2011-08-21 | E-GEOD-28306 | biostudies-arrayexpress
Project description:Burkholderia multivorans is a prominent B. cepacia complex (BCC) species causing infection in people with cystic fibrosis. Despite infection control measures being introduced to reduce the spread of BCC there is a continued emergence of infections by B. multivorans. Our objective was to analyze a global collection of B. multivorans isolates, comparing those from environmental and clinical sources with those from reported outbreaks. Multilocus sequence typing (MLST) was performed on 107 B. multivorans isolates to provide a detailed analysis of the global population biology of this species. MLST resolved 64 B. multivorans sequence types. Twelve of these were globally distributed and associated with human infection; two of these (ST-21 and ST-375) were also composed of environmental isolates. These global lineages included strains previously linked to large outbreaks (e.g., French epidemic clone ST-16). Though few environmental isolates of B. multivorans were available for analysis, of six strains identified, three were identical to strains recovered from cystic fibrosis (CF) infection. Although the ability of B. multivorans to cause CF outbreaks is known, our report here concerning the existence of globally distributed B. multivorans CF strains is a new observation for this emerging B. cepacia complex pathogen and suggests that certain strain types may be better adapted to human infection than others. Common transmission-associated risk factors were not obviously linked to the globally distributed strains; however, the overlap in strains recovered from water environments, industrial products, and human infection suggests that environmental sources may be an important reservoir for infection with B. multivorans.
| S-EPMC2224285 | biostudies-literature
Project description:Burkholderia multivorans is an opportunistic pathogen capable of causing severe disease in patients with cystic fibrosis (CF). Patients may be chronically infected for years, during which the bacterial population evolves in response to unknown forces. Here we analyze the genomic and functional evolution of a B. multivorans infection that was sequentially sampled from a CF patient over 20 years. The population diversified into at least four primary, coexisting clades with distinct evolutionary dynamics. The average substitution rate was only 2.4 mutations/year, but notably, some lineages evolved more slowly, whereas one diversified more rapidly by mostly nonsynonymous mutations. Ten loci, mostly involved in gene expression regulation and lipid metabolism, acquired three or more independent mutations and define likely targets of selection. Further, a broad range of phenotypes changed in association with the evolved mutations; they included antimicrobial resistance, biofilm regulation, and the presentation of lipopolysaccharide O-antigen repeats, which was directly caused by evolved mutations. Additionally, early isolates acquired mutations in genes involved in cyclic di-GMP (c-di-GMP) metabolism that associated with increased c-di-GMP intracellular levels. Accordingly, these isolates showed lower motility and increased biofilm formation and adhesion to CFBE41o- epithelial cells than the initial isolate, and each of these phenotypes is an important trait for bacterial persistence. The timing of the emergence of this clade of more adherent genotypes correlated with the period of greatest decline in the patient's lung function. All together, our observations suggest that selection on B. multivorans populations during long-term colonization of CF patient lungs either directly or indirectly targets adherence, metabolism, and changes in the cell envelope related to adaptation to the biofilm lifestyle. IMPORTANCE Bacteria may become genetically and phenotypically diverse during long-term colonization of cystic fibrosis (CF) patient lungs, yet our understanding of within-host evolutionary processes during these infections is lacking. Here we combined current genome sequencing technologies and detailed phenotypic profiling of the opportunistic pathogen Burkholderia multivorans using sequential isolates sampled from a CF patient over 20 years. The evolutionary history of these isolates highlighted bacterial genes and pathways that were likely subject to strong selection within the host and were associated with altered phenotypes, such as biofilm production, motility, and antimicrobial resistance. Importantly, multiple lineages coexisted for years or even decades within the infection, and the period of diversification within the dominant lineage was associated with deterioration of the patient's lung function. Identifying traits under strong selection during chronic infection not only sheds new light onto Burkholderia evolution but also sets the stage for tailored therapeutics targeting the prevailing lineages associated with disease progression.
| S-EPMC5069766 | biostudies-literature
Project description:During chronic respiratory infections of cystic fibrosis (CF) patients, bacteria adaptively evolve in response to the nutritional and immune environment as well as influence other infecting microbes. The present study was designed to gain insights into the genetic mechanisms underlying adaptation and diversification by the two most prevalent pathogenic species of the Burkholderia cepacia complex (Bcc), B. cenocepacia and B. multivorans. Herein, we study the evolution of both of these species during coinfection of a CF patient for 4.4 years using genome sequences of 9 B. multivorans and 11 B. cenocepacia. This co-infection spanned at least 3 years following initial infection by B. multivorans and ultimately ended in the patient's death by cepacia syndrome. Both species acquired several mutations with accumulation rates of 2.08 (B. cenocepacia) and 2.27 (B. multivorans) SNPs/year. Many of the mutated genes are associated with oxidative stress response, transition metal metabolism, defense mechanisms against antibiotics, and other metabolic alterations consistent with the idea that positive selection might be driven by the action of the host immune system, antibiotic therapy and low oxygen and iron concentrations. Two orthologous genes shared by B. cenocepacia and B. multivorans were found to be under strong selection and accumulated mutations associated with lineage diversification. One gene encodes a nucleotide sugar dehydratase involved in lipopolysaccharide O-antigen (OAg) biosynthesis (wbiI). The other gene encodes a putative two-component regulatory sensor kinase protein required to sense and adapt to oxidative- and heavy metal- inducing stresses. This study contributes to understanding of shared and species-specific evolutionary patterns of B. cenocepacia and B. multivorans evolving in the same CF lung environment.
| S-EPMC7545829 | biostudies-literature
Project description:Multidrug-resistant gram-negative pathogens are a significant health threat. Burkholderia spp. encompass a complex subset of gram-negative bacteria with a wide range of biological functions that include human, animal, and plant pathogens. The treatment of infections caused by Burkholderia spp. is problematic due to their inherent resistance to multiple antibiotics. The major ?-lactam resistance determinant expressed in Burkholderia spp. is a class A ?-lactamase of the PenA family. In this study, significant amino acid sequence heterogeneity was discovered in PenA (37 novel variants) within a panel of 48 different strains of Burkholderia multivorans isolated from individuals with cystic fibrosis. Phylogenetic analysis distributed the 37 variants into 5 groups based on their primary amino acid sequences. Amino acid substitutions were present throughout the entire ?-lactamase and did not congregate to specific regions of the protein. The PenA variants possessed 5 to 17 single amino acid changes. The N189S and S286I substitutions were most prevalent and found in all variants. Due to the sequence heterogeneity in PenA, a highly conserved peptide (18 amino acids) within PenA was chosen as the antigen for polyclonal antibody production in order to measure expression of PenA within the 48 clinical isolates of B. multivorans. Characterization of the anti-PenA peptide antibody, using immunoblotting approaches, exposed several unique features of this antibody (i.e., detected <500 pg of purified PenA, all 37 PenA variants in B. multivorans, and Pen-like ?-lactamases from other species within the Burkholderia cepacia complex). The significant sequence heterogeneity found in PenA may have occurred due to selective pressure (e.g., exposure to antimicrobial therapy) within the host. The contribution of these changes warrants further investigation.
| S-EPMC6173980 | biostudies-literature
Project description:Background:Individuals with cystic fibrosis (CF) have persistent lung infections, necessitating the frequent use of antibiotics for pulmonary exacerbations. Some respiratory pathogens have intrinsic resistance to the currently available antibiotics, and any pathogen may acquire resistance over time, posing a challenge to CF care. Gaseous nitric oxide has been shown to have antimicrobial activity against a wide variety of microorganisms, including common CF pathogens, and offers a potential inhaled antimicrobial therapy. Case Presentation. Here, we present the case of a 16-year-old female with CF who experienced a precipitous decline in lung function over the prior year in conjunction with worsening antibiotic resistance of her primary pathogen, Burkholderia multivorans. She received 46 intermittent inhalations of 160 parts-per-million nitric oxide over a 28-day period. The gas was administered via a mechanical ventilator fitted with nitrogen dioxide scavenging chambers. Conclusions:High-dose inhaled nitric oxide was safe, well tolerated, and showed clinical benefit in an adolescent with cystic fibrosis and pulmonary colonization with Burkholderia multivorans.
| S-EPMC7334765 | biostudies-literature
Project description:BackgroundThere is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic-resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died.MethodsPhages were given via nebulization through the mechanical ventilation circuit. Remnant respiratory specimens and serum were collected. We quantified phage and bacterial deoxyribonucleic acid (DNA) using quantitative polymerase chain reaction, and tested phage neutralization in the presence of patient serum. We performed whole genome sequencing and antibiotic and phage susceptibility testing on 15 B. multivorans isolates. Finally, we extracted lipopolysaccharide (LPS) from two isolates and visualized their LPS using gel electrophoresis.ResultsPhage therapy was temporally followed by a temporary improvement in leukocytosis and hemodynamics, followed by worsening leukocytosis on day 5, deterioration on day 7, and death on day 8. We detected phage DNA in respiratory samples after 6 days of nebulized phage therapy. Bacterial DNA in respiratory samples decreased over time, and no serum neutralization was detected. Isolates collected between 2001 and 2020 were closely related but differed in their antibiotic and phage susceptibility profiles. Early isolates were not susceptible to the phage used for therapy, while later isolates, including two isolates collected during phage therapy, were susceptible. Susceptibility to the phage used for therapy was correlated with differences in O-antigen profiles of an early versus a late isolate.ConclusionsThis case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.
| S-EPMC10085838 | biostudies-literature
Project description:Pseudomonas aeruginosa strain 18A is a clinical, nonclonal isolate retrieved from the sputum of a chronically infected cystic fibrosis patient. The genome of 18A was sequenced for comparison with environmental and clinical isolates to identify genes that might facilitate its persistence during infection.
| S-EPMC3622990 | biostudies-other
Project description:Burkholderia multivorans comprises opportunistic bacteria infecting hosts such as cystic fibrosis (CF) patients. Bcc long-term infection of CF patient airways has been associated with emergence of phenotypic variation including the mucoid-to-nonmucoid colony morphotype. Here we studied three Burkholderia multivorans clonal isolates (mucoid D2095 (BM11L), and nonmucoid D2214G and D2214P) and a laboratory nonmucoid variant (BM11L-nmv1) obtained under prolonged stationary phase. The aim is to identify possible traits associated to the different morphotypes and find possible mechanisms for this morphotypic variation.
2018-06-22 | GSE111467 | GEO