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Biomolecules Aug 2021BceF is a bacterial tyrosine kinase (BY-kinase) from , a Gram-negative bacterium accountable for respiratory infections in immunocompromised and cystic fibrosis...
BceF is a bacterial tyrosine kinase (BY-kinase) from , a Gram-negative bacterium accountable for respiratory infections in immunocompromised and cystic fibrosis patients. BceF is involved in the production of exopolysaccharides secreted to the biofilm matrix and promotes resistant and aggressive infections. BY-kinases share no homology with mammalian kinases, and thereby offer a means to develop novel and specific antivirulence drugs. Here, we report the crystal structure of the BceF kinase domain at 1.85 Å resolution. The isolated BceF kinase domain is assembled as a dimer in solution and crystallized as a dimer in the asymmetric unit with endogenous adenosine-diphosphate bound at the active sites. The low enzymatic efficiency measured in solution may be explained by the partial obstruction of the active sites at the crystallographic dimer interface. This study provides insights into self-assembly and the specific activity of isolated catalytic domains. Several unique variations around the active site compared to other BY-kinases may allow for structure-based design of specific inhibitors to target virulence.
Topics: Bacterial Proteins; Biofilms; Burkholderia cepacia; Crystallography, X-Ray; Humans; Protein Structure, Secondary; Protein Structure, Tertiary; Protein-Tyrosine Kinases; Virulence
PubMed: 34439861
DOI: 10.3390/biom11081196 -
The European Respiratory Journal Feb 2001Burkholderia cepacia is a plant phytogen and is known as a hardy and versatile organism. Over the past two decades it has emerged as a pathogen in the cystic fibrosis... (Review)
Review
Burkholderia cepacia is a plant phytogen and is known as a hardy and versatile organism. Over the past two decades it has emerged as a pathogen in the cystic fibrosis (CF) community, with devastating effects. Pulmonary colonisation can lead to an accelerated decline in lung function. In some cases, it causes a rapid and progressive pneumonic illness termed "cepacia syndrome", which is untreatable and fatal. B. cepacia is inherently resistant to multiple antibiotics and highly transmissible and virulent strains have been identified. CF patients colonised with the organism have to be segregated from their peers to try to prevent cross-infection. However, the pathogenicity of B. cepacia is not limited to CF. Other groups, such as individuals with chronic granulomatous disease and immunocompromised patients are vulnerable and it has caused disease in healthy individuals. However, the agricultural and petrochemical industries are attempting to exploit properties of B. cepacia for use as a biopesticide and biodegradation agent. This article provides an up to date review of clinically based literature on the Burkholderia cepacia complex, highlighting clinical management issues for both cystic fibrosis and non-cystic fibrosis patients. The article also addresses the potential conflict between medicine and agriculture on plans to reintroduce strains of Burkholderia cepacia back into the environment.
Topics: Burkholderia Infections; Burkholderia cepacia; Cross Infection; Cystic Fibrosis; Drug Resistance, Microbial; Humans; Lung Diseases; Pest Control, Biological; Virulence
PubMed: 11334134
DOI: 10.1183/09031936.01.17202950 -
Frontiers in Cellular and Infection... 2013The genus Burkholderia consists of diverse species which includes both "friends" and "foes." Some of the "friendly" Burkholderia spp. are extensively used in the... (Review)
Review
The genus Burkholderia consists of diverse species which includes both "friends" and "foes." Some of the "friendly" Burkholderia spp. are extensively used in the biotechnological and agricultural industry for bioremediation and biocontrol. However, several members of the genus including B. pseudomallei, B. mallei, and B. cepacia, are known to cause fatal disease in both humans and animals. B. pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively, while B. cepacia infection is lethal to cystic fibrosis (CF) patients. Due to the high rate of infectivity and intrinsic resistance to many commonly used antibiotics, together with high mortality rate, B. mallei and B. pseudomallei are considered to be potential biological warfare agents. Treatments of the infections caused by these bacteria are often unsuccessful with frequent relapse of the infection. Thus, we are at a crucial stage of the need for Burkholderia vaccines. Although the search for a prophylactic therapy candidate continues, to date development of vaccines has not advanced beyond research to human clinical trials. In this article, we review the current research on development of safe vaccines with high efficacy against B. pseudomallei, B. mallei, and B. cepacia. It can be concluded that further research will enable elucidation of the potential benefits and risks of Burkholderia vaccines.
Topics: Animals; Bacterial Vaccines; Burkholderia Infections; Burkholderia cepacia; Burkholderia mallei; Burkholderia pseudomallei; Cost-Benefit Analysis; Cystic Fibrosis; Glanders; Humans; Melioidosis; Models, Animal; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Inactivated
PubMed: 23386999
DOI: 10.3389/fcimb.2013.00005 -
Microbiology and Immunology Feb 2020Burkholderia cepacia complex (Bcc) are opportunistic pathogens implicated with nosocomial infections, and high rates of morbidity and mortality, especially in... (Review)
Review
Burkholderia cepacia complex (Bcc) are opportunistic pathogens implicated with nosocomial infections, and high rates of morbidity and mortality, especially in individuals with cystic fibrosis (CF). B. cepacia are naturally resistant to different classes of antibiotics, and can subvert the host innate immune responses by producing quorum sensing (QS) controlled virulence factors and biofilms. It still remains a conundrum as to how exactly the bacterium survives the intracellular environment within the host cells of CF patients and immunocompromised individuals although the bacterium can invade human lung epithelial cells, neutrophils, and murine macrophages. The mechanisms associated with intracellular survival in the airway epithelial cells and the role of QS and virulence factors in B. cepacia infections in cystic fibrosis remain largely unclear. The current review focuses on understanding the role of QS-controlled virulence factors and biofilms, and provides additional impetus to understanding the potentials of QS-inhibitory strategies against B. cepacia.
Topics: Animals; Biofilms; Burkholderia Infections; Burkholderia cepacia; Burkholderia cepacia complex; Communicable Diseases, Emerging; Cross Infection; Cystic Fibrosis; Cytokine Release Syndrome; Drug Resistance, Multiple, Bacterial; Humans; Immune Evasion; Immunocompromised Host; Inflammation; Lipase; Lipopolysaccharides; Lung; Macrophages; Metalloendopeptidases; Mice; Neutrophils; Quorum Sensing; Siderophores; Virulence Factors
PubMed: 31769530
DOI: 10.1111/1348-0421.12762 -
The Journal of General and Applied... Aug 2020The present study reports on the cloning, expression and characterization of catechol 1,2-dioxygenase (CAT) of bacterial strains isolated from dioxin-contaminated soils...
The present study reports on the cloning, expression and characterization of catechol 1,2-dioxygenase (CAT) of bacterial strains isolated from dioxin-contaminated soils in Vietnam. Two isolated bacterial strains DF2 and DF4 were identified as Burkholderia cepacia based on their 16S rRNA sequences. Their genes coding CAT was amplified with a specific pair of primers. Recombinant CAT (rCAT) was expressed in E. coli M15 cells and its activity was confirmed by the detection of cis,cis-muconic acid, a product from catechol, by high-performance liquid chromatography (HPLC) analysis. The rCAT of DF4 had an optimal pH and temperature of 7 and 30°C, respectively. Metal ions, such as Zn and Mn, and surfactants, such as SDS, Tween 20 and Triton X100, strongly inhibited enzyme activity, while K slightly increased the activity.
Topics: Burkholderia cepacia; Catechol 1,2-Dioxygenase; Catechols; Cloning, Molecular; Dioxins; Genes, Bacterial; Hydrogen-Ion Concentration; Metals; Soil Microbiology; Soil Pollutants; Surface-Active Agents; Temperature
PubMed: 31723074
DOI: 10.2323/jgam.2019.06.002 -
Indian Journal of Pathology &... 2023Burkholderia cepacia infections are common among immunocompromised patients but multiple reports have shown that it can affect immunocompetent patients also. We are...
Burkholderia cepacia infections are common among immunocompromised patients but multiple reports have shown that it can affect immunocompetent patients also. We are reporting two patients with multiple liver and splenic abscesses caused by Burkholderia cepacia. First case is a 54-year-old diabetic male presenting with fever, abdominal pain, bilateral lower limb weakness, and incontinence of urine. Second case is a 41-year-old male presenting with fever and confusion. Both had liver and splenic abscesses. Pus aspirated from the abscesses grew Burkholderia cepacia. Both responded to cotrimoxazole. Our case report emphasizes growing incidence of Burkholderia cepacia in immunocompetent patients.
Topics: Humans; Male; Adult; Middle Aged; Burkholderia cepacia; Abscess; Splenic Diseases; Burkholderia Infections; Liver
PubMed: 36656234
DOI: 10.4103/ijpm.ijpm_702_21 -
The American Journal of Tropical... Dec 2020Patients undergoing hemodialysis are at an increased risk for bloodstream infections (BSIs). Infection usually occurs because of contamination of water supply, water...
Patients undergoing hemodialysis are at an increased risk for bloodstream infections (BSIs). Infection usually occurs because of contamination of water supply, water treatment, distribution systems, or reprocessing dialyzers. Here, we report an outbreak of BSIs caused by Stenotrophomonas maltophilia (n = 21) and Burkholderia cepacia (n = 22) among dialyzed patients at a large hemodialysis center in Brazil. Overall, three patients died (7%), two of which had bacteremia caused by S. maltophilia and the other had a B. cepacia infection. We collected water samples from different points of the hemodialysis system for culture and typing. Genetic patterns were identified through polymerase chain reaction-random amplified polymorphic DNA (PCR-RAPD) and pulsed-field gel electrophoresis. The same genotypes of S. maltophilia and B. cepacia recovered from blood cultures were found in dialysis water. Also, multiple genetic profiles were identified among water isolates, suggesting heavy contamination. Bacteremia cases persisted even after implementing standard control measures, which led us to believe that the piping system was contaminated with microbial biofilms. Soon after we changed the entire plumbing system, reported cases dropped back to the number typically expected, and the outbreak came to an end.
Topics: Adult; Aged; Aged, 80 and over; Brazil; Burkholderia Infections; Burkholderia cepacia; Disease Outbreaks; Disinfection; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Renal Dialysis; Sepsis; Stenotrophomonas maltophilia
PubMed: 33319730
DOI: 10.4269/ajtmh.20-1035 -
Microbiology Spectrum Mar 2024and are Gram-negative, soil-dwelling bacteria that are found in a wide variety of environmental niches. While is the causative agent of melioidosis in humans and...
and are Gram-negative, soil-dwelling bacteria that are found in a wide variety of environmental niches. While is the causative agent of melioidosis in humans and animals, members of the complex typically only cause disease in immunocompromised hosts. In this study, we report the identification of strains isolated from either patients or soil in Laos and Thailand that express a -like 6-deoxyheptan capsular polysaccharide (CPS). These strains were initially identified based on their positive reactivity in a latex agglutination assay that uses the CPS-specific monoclonal antibody (mAb) 4B11. Mass spectrometry and sequencing confirmed the identity of these isolates as (formerly genomovar I). Total carbohydrates extracted from cell pellets reacted with CPS-specific mAbs MCA147, 3C5, and 4C4, but did not react with the lipopolysaccharide-specific mAb Pp-PS-W. Whole genome sequencing of the isolates revealed the presence of genes demonstrating significant homology to those comprising the CPS biosynthetic gene cluster. Collectively, our results provide compelling evidence that strains expressing the same CPS as co-exist in the environment alongside . Since CPS is a target that is often used for presumptive identification of , it is possible that the occurrence of these unique strains may complicate the diagnosis of melioidosis.IMPORTANCE, the etiologic agent of melioidosis, is an important cause of morbidity and mortality in tropical and subtropical regions worldwide. The 6-deoxyheptan capsular polysaccharide (CPS) expressed by this bacterial pathogen is a promising target antigen that is useful for rapidly diagnosing melioidosis. Using assays incorporating CPS-specific monoclonal antibodies, we identified both clinical and environmental isolates of that express the same CPS antigen as . Because of this, it is important that staff working in melioidosis-endemic areas are aware that these strains co-exist in the same niches as and do not solely rely on CPS-based assays such as latex-agglutination, AMD Plus Rapid Tests, or immunofluorescence tests for the definitive identification of isolates.
Topics: Animals; Humans; Burkholderia pseudomallei; Melioidosis; Burkholderia cepacia; Polysaccharides; Antibodies, Monoclonal; Soil
PubMed: 38299821
DOI: 10.1128/spectrum.03321-23 -
Thorax Jan 1999
Topics: Bronchiectasis; Burkholderia Infections; Burkholderia cepacia; Humans; Immunocompromised Host
PubMed: 10343643
DOI: 10.1136/thx.54.1.91b -
International Journal of Infectious... Feb 2019The detailed epidemiological and molecular characterization of an outbreak of Burkholderia cepacia at a neurotrauma intensive care unit of a level 1 trauma centre is...
OBJECTIVE
The detailed epidemiological and molecular characterization of an outbreak of Burkholderia cepacia at a neurotrauma intensive care unit of a level 1 trauma centre is described. The stringent infection control interventions taken to successfully curb this outbreak are emphasized.
METHODS
The clinical and microbiological data for those patients who had more than one blood culture that grew B. cepacia were reviewed. Bacterial identification and antimicrobial susceptibility testing was done using automated Vitek 2 systems. Prospective surveillance, environmental sampling, and multilocus sequence typing (MLST) were performed for extensive source tracking. Intensive infection control measures were taken to further control the hospital spread.
RESULTS
Out of a total 48 patients with B. cepacia bacteraemia, 15 (31%) had central line-associated blood stream infections. Two hundred and thirty-one environmental samples were collected and screened, and only two water samples grew B. cepacia with similar phenotypic characteristics. The clinical strains characterized by MLST typing were clonal. However, isolates from the water represented a novel strain type (ST-1289). Intensive terminal cleaning, disinfection of the water supply, and the augmentation of infection control activities were done to curb the outbreak. A subsequent reduction in bacteraemia cases was observed.
CONCLUSION
Early diagnosis and appropriate therapy, along with the rigorous implementation of essential hospital infection control practices is required for successful containment of this pathogen and to curb such an outbreak.
Topics: Adolescent; Adult; Aged; Bacteremia; Burkholderia Infections; Burkholderia cepacia; Cross Infection; Disease Outbreaks; Female; Humans; Infection Control; Intensive Care Units; Male; Middle Aged; Multilocus Sequence Typing; Young Adult
PubMed: 30342249
DOI: 10.1016/j.ijid.2018.10.008