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Frontiers in Cellular and Infection... 2021The genus contains over 80 different Gram-negative species including both plant and human pathogens, the latter of which can be classified into one of two groups: the... (Review)
Review
The genus contains over 80 different Gram-negative species including both plant and human pathogens, the latter of which can be classified into one of two groups: the complex (Bpc) or the complex (Bcc). Bpc pathogens and are highly virulent, and both have considerable potential for use as Tier 1 bioterrorism agents; thus there is great interest in the development of novel vaccines and therapeutics for the prevention and treatment of these infections. While Bcc pathogens , , and are not considered bioterror threats, the incredible impact these infections have on the cystic fibrosis community inspires a similar demand for vaccines and therapeutics for the prevention and treatment of these infections as well. Understanding how these pathogens interact with and evade the host immune system will help uncover novel therapeutic targets within these organisms. Given the important role of the complement system in the clearance of bacterial pathogens, this arm of the immune response must be efficiently evaded for successful infection to occur. In this review, we will introduce the species to be discussed, followed by a summary of the complement system and known mechanisms by which pathogens interact with this critical system to evade clearance within the host. We will conclude with a review of literature relating to the interactions between the herein discussed species and the host complement system, with the goal of highlighting areas in this field that warrant further investigation.
Topics: Burkholderia; Burkholderia Infections; Burkholderia pseudomallei; Complement System Proteins; Humans; Immune Evasion; Melioidosis
PubMed: 34660335
DOI: 10.3389/fcimb.2021.701362 -
Frontiers in Immunology 2022Inflammatory caspases detect cytosol-invasive Gram-negative bacteria by monitoring for the presence of LPS in the cytosol. This should provide defense against the... (Review)
Review
Inflammatory caspases detect cytosol-invasive Gram-negative bacteria by monitoring for the presence of LPS in the cytosol. This should provide defense against the cytosol-invasive and species by lysing the infected cell pyroptosis. However, recent evidence has shown caspase-11 and gasdermin D activation can result in two different outcomes: pyroptosis and autophagy. complex has the ability invade the cytosol but is unable to inhibit caspase-11 and gasdermin D. Yet instead of activating pyroptosis during infection with these bacteria, the autophagy pathway is stimulated through caspases and gasdermin D. In contrast, can invade the cytosol where caspasae-11 and gasdermin D is activated but the result is pyroptosis of the infected cell. In this review we propose a hypothetical model to explain why autophagy would be the solution to kill one type of species, but another species is killed by pyroptosis. For pathogens with high virulence, pyroptosis is the only solution to kill bacteria. This explains why some pathogens, such as have evolved methods to inhibit caspase-11 and gasdermin D as well as autophagy. We also discuss similar regulatory steps that affect caspase-1 that may permit the cell to forbear undergoing pyroptosis after caspase-1 activates in response to bacteria with partially effective virulence factors.
Topics: Autophagy; Caspase 1; Caspases; Cytosol; Pyroptosis
PubMed: 35422805
DOI: 10.3389/fimmu.2022.871190 -
Annals of Medicine Dec 2024complex () is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic... (Review)
Review
complex () is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic fibrosis (CF), can cause severe lung infections that lead to accelerated lung damage, which can be complicated by necrotizing pneumonia accompanied by high fevers, leucocytosis, and bacteraemia, which commonly causes fatal outcomes. Specifically, infection by is considered an exclusion criterion for lung transplantation. The species of exhibit both genetic and phenotypic hypervariability that complicate their accurate microbiological identification. Automated methods such as MALDI-TOF can err in the determination of species. Their slow growth even in selective agars and the absence of international consensuses on the optimal conditions for their isolation make early diagnosis a difficult challenge to overcome. The absence of correlations between antibiograms and clinical results has resulted in the absence of standardized cut-off values of antimicrobial susceptibility, a fact that brings a latent risk since incorrect antibiotic therapy can induce the selection of more aggressive variants that worsen the clinical picture of the host, added to the absence of a clear therapeutic guide for the eradication of pulmonary infections by in patients with CF, resulting in frequently ineffective treatments. There is an urgent need to standardize methods and diagnostic tools that would allow an early and accurate diagnosis, as well as to perform clinical studies of the effectiveness of available antibiotics to eradicate infections, which would allow us to establish standardized therapeutic schemes for -infected patients.
Topics: Humans; Cystic Fibrosis; Burkholderia cepacia complex; Lung Transplantation; Anti-Bacterial Agents; Bacteremia
PubMed: 38261606
DOI: 10.1080/07853890.2024.2307503 -
Frontiers in Microbiology 2015The Burkholderia cepacia complex (Bcc) is a collection of closely related, genetically distinct, ecologically diverse species known to cause life-threatening infections... (Review)
Review
The Burkholderia cepacia complex (Bcc) is a collection of closely related, genetically distinct, ecologically diverse species known to cause life-threatening infections in cystic fibrosis (CF) patients. By virtue of a flexible genomic structure and diverse metabolic activity, Bcc bacteria employ a wide array of virulence factors for pathogenesis in CF patients and have developed resistance to most of the commonly used antibiotics. However, the mechanism of pathogenesis and antibiotic resistance is still not fully understood. This mini review discusses the established and potential virulence determinants of Bcc and some of the contemporary strategies including transcriptomics and proteomics used to identify these traits. We also propose the application of metabolic profiling, a cost-effective modern-day approach to achieve new insights.
PubMed: 26217312
DOI: 10.3389/fmicb.2015.00668 -
Journal of Bacteriology May 2021Bacterial genomes can be methylated at particular motifs by methyltransferases (MTs). This DNA modification allows restriction endonucleases (REs) to discriminate...
Bacterial genomes can be methylated at particular motifs by methyltransferases (MTs). This DNA modification allows restriction endonucleases (REs) to discriminate between self and foreign DNA. While the accepted primary function of such restriction modification (RM) systems is to degrade incoming foreign DNA, other roles of RM systems and lone RE or MT components have been found in genome protection, stability, and the regulation of various phenotypes. The Burkholderia cepacia complex (Bcc) is a group of closely related opportunistic pathogens with biotechnological potential. Here, we constructed and analyzed mutants lacking various RM components in the clinical Bcc isolate Burkholderia cenocepacia H111 and used single-molecule, real-time (SMRT) sequencing of single mutants to assign the B. cenocepacia H111 MTs to their cognate motifs. DNA methylation is shown to affect biofilm formation, cell shape, motility, siderophore production, and membrane vesicle production. Moreover, DNA methylation had a large effect on the maintenance of the Bcc virulence megaplasmid pC3. Our data also suggest that the MT-encoding gene, which is essential in H111 and is located within a prophage, is required for maintaining the bacteriophage in a lysogenic state, thereby ensuring a constant, low level of phage production within the bacterial population. While the genome sequence determines an organism's proteins, methylation of the nucleotides themselves can confer additional properties. In bacteria, MTs modify specific nucleotide motifs to allow discrimination of "self" from "nonself" DNA, e.g., from bacteriophages. Restriction enzymes detect "nonself" methylation patterns and cut foreign DNA. Furthermore, methylation of promoter regions can influence gene expression and hence affect various phenotypes. In this study, we determined the methylated motifs of four strains from the Burkholderia cepacia complex of opportunistic pathogens. We deleted all genes encoding the restriction and modification components in one of these strains, Burkholderia cenocepacia H111. It is shown that DNA methylation affects various phenotypic traits, the most noteworthy being lysogenicity of a bacteriophage and maintenance of a virulence megaplasmid.
Topics: Bacterial Proteins; Burkholderia cepacia complex; DNA-Directed DNA Polymerase; Epigenome; Gene Deletion; Gene Expression Regulation, Bacterial; Genome, Bacterial; Iron; Movement; Mutation; Phylogeny; Real-Time Polymerase Chain Reaction; Single Molecule Imaging; Transcriptome; Whole Genome Sequencing
PubMed: 33753468
DOI: 10.1128/JB.00683-20 -
Journal of Clinical Medicine Sep 2023Chronic granulomatous disease (CGD) is an inborn error of immunity due to defects in the transport or function of subunits of nicotinamide adenine dinucleotide phosphate... (Review)
Review
Chronic granulomatous disease (CGD) is an inborn error of immunity due to defects in the transport or function of subunits of nicotinamide adenine dinucleotide phosphate oxidase, the enzyme that generates the phagocyte respiratory burst responsible for intracellular killing of engulfed micro-organisms. Patients present with infectious or inflammatory complications. Common bacterial pathogens include and complex. Fungal pathogens include species, particularly . Inflammatory complications most commonly manifest as inflammatory bowel disease or lung disease. Granulomata are the distinguishing histological feature. Haematopoietic stem cell transplantation (HSCT) was first considered for CGD in the early 1970's. Since then, refinements in transplant technique, donor selection, conditioning regimens, and graft engineering have widened the option of HSCT to most patients with CGD. This review charts the progress made in HSCT for CGD.
PubMed: 37763024
DOI: 10.3390/jcm12186083 -
Frontiers in Genetics 2020Recombination and positive selection are two key factors that play a vital role in pathogenic microorganisms' population adaptation and diversification. The complex...
Recombination and positive selection are two key factors that play a vital role in pathogenic microorganisms' population adaptation and diversification. The complex (Bcc) represents bacterial species with high similarity, which can cause severe infections among cases suffering from the chronic granulomatous disorder and cystic fibrosis (CF). At present, no genome-wide study has been carried out focusing on investigating the core genome of Bcc associated with the two evolutionary forces. The general characteristics of the core genome of Bcc species remain scarce as well. In this study, we explored the core orthologous genes of 116 Bcc strains using comparative genomic analysis and studied the two adaptive evolutionary forces: recombination and positive selection. We estimated 1005 orthogroups consisting entirely of single copy genes. These single copy orthologous genes in some Cluster of Orthologous Groups (COG) categories showed significant differences in the comparison of several evolutionary properties, and the encoding proteins were relatively simple and compact. Our findings showed that 5.8% of the core orthologous genes strongly supported recombination; in the meantime, 1.1% supported positive selection. We found that genes involved in protein synthesis as well as material transport and metabolism are favored by selection pressure. More importantly, homologous recombination contributed more genetic variation to a large number of genes and largely maintained the genetic cohesion in Bcc. This high level of recombination between Bcc species blurs their taxonomic boundaries, which leads Bcc species to be difficult or impossible to distinguish phenotypically and genotypically.
PubMed: 32528528
DOI: 10.3389/fgene.2020.00506 -
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 -
Antibiotics (Basel, Switzerland) May 2022Lung transplant recipients are at higher risk to develop infectious diseases due to multi-drug resistant pathogens, which often chronically colonize the respiratory... (Review)
Review
Lung transplant recipients are at higher risk to develop infectious diseases due to multi-drug resistant pathogens, which often chronically colonize the respiratory tract before transplantation. The emergence of these difficult-to-treat infections is a therapeutic challenge, and it may represent a contraindication to lung transplantation. New antibiotic options are currently available, but data on their efficacy and safety in the transplant population are limited, and clinical evidence for choosing the most appropriate antibiotic therapy is often lacking. In this review, we provide a summary of the best evidence available in terms of choice of antibiotic and duration of therapy for MDR/XDR , complex, complex and spp. infections in lung transplant candidates and recipients.
PubMed: 35625256
DOI: 10.3390/antibiotics11050612