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Expert Opinion on Drug Discovery Jul 2021: The increasing threat of antibiotic-resistant pathogens makes it imperative that new antibiotics to combat them are discovered. is a genus of Gram-negative,... (Review)
Review
: The increasing threat of antibiotic-resistant pathogens makes it imperative that new antibiotics to combat them are discovered. is a genus of Gram-negative, non-sporulating bacteria. While ubiquitous and capable of growing within plants and groundwater, they are primarily soil-dwelling organisms. These include the more virulent forms of such as , and the complex (Bcc).: This review provides a synopsis of current research on the natural products isolated from the genus . The authors also cover the research on the drug discovery efforts that have been performed on the natural products derived from .: Though has a small number of pathogenic species, the majority of the genus is avirulent and almost all members of the genus are capable of producing useful antimicrobial products that could potentially lead to the development of novel therapeutics against infectious diseases. The need for discovery of new antibiotics is urgent due to the ever-increasing prevalence of antibiotic-resistant pathogens, coupled with the decline in the discovery of new antibiotics.
Topics: Biological Products; Burkholderia; Burkholderia Infections; Burkholderia pseudomallei; Drug Discovery; Humans
PubMed: 33467922
DOI: 10.1080/17460441.2021.1877655 -
Genomics Jan 2022Here the pangenome analysis of Burkholderia sensu lato (s.l.) was performed for the first time, together with an updated analysis of the pangenome of Burkholderia sensu...
Here the pangenome analysis of Burkholderia sensu lato (s.l.) was performed for the first time, together with an updated analysis of the pangenome of Burkholderia sensu stricto, and Burkholderia cepacia complex (Bcc) focusing on the Bcc B. catarinensis specific features of its re-sequenced genome. The pangenome of Burkholderia s.l., Burkholderia s.s., and of the Bcc was open, composed of more than 96% of accessory genes, and more than 62% of unknown genes. Functional annotations showed that secondary metabolism genes belonged to the variable portion of genomes, which might explain their production of several compounds with varied bioactivities. Taken together, this work showed the great variability and uniqueness of these genomes and revealed an underexplored unknown potential in poorly characterized genes. Regarding B. catarinensis 89, its genome harbors genes related to hydrolases production and plant growth promotion. This draft genome will be valuable for further investigation of its biotechnological potentials.
Topics: Burkholderia; Burkholderia cepacia complex
PubMed: 34780935
DOI: 10.1016/j.ygeno.2021.11.011 -
Research in Microbiology Apr 2017A number of insects establish symbiotic associations with beneficial microorganisms in various manners. The bean bug Riptortus pedestris and allied stink bugs possess an... (Review)
Review
A number of insects establish symbiotic associations with beneficial microorganisms in various manners. The bean bug Riptortus pedestris and allied stink bugs possess an environmentally acquired Burkholderia symbiont in their midgut crypts. Unlike other insect endosymbionts, the Burkholderia symbiont is easily culturable and genetically manipulatable outside the host. In conjunction with the experimental advantages of the host insect, the Riptortus-Burkholderia symbiosis is an ideal model system for elucidating the molecular bases underpinning insect-microbe symbioses, which opens a new window in the research field of insect symbiosis. This review summarizes current knowledge of this system and discusses future perspectives.
Topics: Animals; Biological Evolution; Burkholderia; Heteroptera; Intestines; Microbiota; Symbiosis
PubMed: 27965151
DOI: 10.1016/j.resmic.2016.11.005 -
Journal of Natural Products Jul 2019bacteria are multifaceted organisms that are ecologically and metabolically diverse. The genus has gained prominence because it includes human pathogens; however, many...
bacteria are multifaceted organisms that are ecologically and metabolically diverse. The genus has gained prominence because it includes human pathogens; however, many strains are nonpathogenic and have desirable characteristics such as beneficial plant associations and degradation of pollutants. The diversity of the genus is reflected within the large genomes that feature multiple replicons. genomes encode a plethora of natural products with potential therapeutic relevance and biotechnological applications. This review highlights as an emerging source of natural products. An overview of the taxonomy of the genus, which is currently being revised, is provided. We then present a curated compilation of natural products isolated from sensu lato and analyze their characteristics in terms of biosynthetic class, discovery method, and bioactivity. Finally, we describe and discuss genome characteristics and highlight the biosynthesis of a select number of natural products that are encoded in unusual biosynthetic gene clusters. The availability of >1000 genomes in public databases provides an opportunity to realize the genetic potential of this underexplored taxon for natural product discovery.
Topics: Biological Products; Burkholderia; Genes, Bacterial
PubMed: 31294966
DOI: 10.1021/acs.jnatprod.8b01068 -
Viruses Jul 2021The increasing prevalence and worldwide distribution of multidrug-resistant bacterial pathogens is an imminent danger to public health and threatens virtually all... (Review)
Review
The increasing prevalence and worldwide distribution of multidrug-resistant bacterial pathogens is an imminent danger to public health and threatens virtually all aspects of modern medicine. Particularly concerning, yet insufficiently addressed, are the members of the complex (Bcc), a group of at least twenty opportunistic, hospital-transmitted, and notoriously drug-resistant species, which infect and cause morbidity in patients who are immunocompromised and those afflicted with chronic illnesses, including cystic fibrosis (CF) and chronic granulomatous disease (CGD). One potential solution to the antimicrobial resistance crisis is phage therapy-the use of phages for the treatment of bacterial infections. Although phage therapy has a long and somewhat checkered history, an impressive volume of modern research has been amassed in the past decades to show that when applied through specific, scientifically supported treatment strategies, phage therapy is highly efficacious and is a promising avenue against drug-resistant and difficult-to-treat pathogens, such as the Bcc. In this review, we discuss the clinical significance of the Bcc, the advantages of phage therapy, and the theoretical and clinical advancements made in phage therapy in general over the past decades, and apply these concepts specifically to the nascent, but growing and rapidly developing, field of Bcc phage therapy.
Topics: Bacteriophages; Burkholderia cepacia complex; Humans; Phage Therapy
PubMed: 34372537
DOI: 10.3390/v13071331 -
Secondary metabolites from the Burkholderia pseudomallei complex: structure, ecology, and evolution.Journal of Industrial Microbiology &... Oct 2020Bacterial secondary metabolites play important roles in promoting survival, though few have been carefully studied in their natural context. Numerous gene clusters code... (Review)
Review
Bacterial secondary metabolites play important roles in promoting survival, though few have been carefully studied in their natural context. Numerous gene clusters code for secondary metabolites in the genomes of members of the Bptm group, made up of three closely related species with distinctly different lifestyles: the opportunistic pathogen Burkholderia pseudomallei, the non-pathogenic saprophyte Burkholderia thailandensis, and the host-adapted pathogen Burkholderia mallei. Several biosynthetic gene clusters are conserved across two or all three species, and this provides an opportunity to understand how the corresponding secondary metabolites contribute to survival in different contexts in nature. In this review, we discuss three secondary metabolites from the Bptm group: bactobolin, malleilactone (and malleicyprol), and the 4-hydroxy-3-methyl-2-alkylquinolines, providing an overview of each of their biosynthetic pathways and insight into their potential ecological roles. Results of studies on these secondary metabolites provide a window into how secondary metabolites contribute to bacterial survival in different environments, from host infections to polymicrobial soil communities.
Topics: Biosynthetic Pathways; Burkholderia; Burkholderia mallei; Burkholderia pseudomallei; Lactones; Multigene Family
PubMed: 33052546
DOI: 10.1007/s10295-020-02317-0 -
PloS One 2021The Burkholderia pseudomallei phylogenetic cluster includes B. pseudomallei, B. mallei, B. thailandensis, B. oklahomensis, B. humptydooensis and B. singularis. Regarded...
The Burkholderia pseudomallei phylogenetic cluster includes B. pseudomallei, B. mallei, B. thailandensis, B. oklahomensis, B. humptydooensis and B. singularis. Regarded as the only pathogenic members of this group, B. pseudomallei and B. mallei cause the diseases melioidosis and glanders, respectively. Additionally, variant strains of B. pseudomallei and B. thailandensis exist that include the geographically restricted B. pseudomallei that express a B. mallei-like BimA protein (BPBM), and B. thailandensis that express a B. pseudomallei-like capsular polysaccharide (BTCV). To establish a PCR-based assay for the detection of pathogenic Burkholderia species or their variants, five PCR primers were designed to amplify species-specific sequences within the bimA (Burkholderia intracellular motility A) gene. Our multiplex PCR assay could distinguish pathogenic B. pseudomallei and BPBM from the non-pathogenic B. thailandensis and the BTCV strains. A second singleplex PCR successfully discriminated the BTCV from B. thailandensis. Apart from B. humptydooensis, specificity testing against other Burkholderia spp., as well as other Gram-negative and Gram-positive bacteria produced a negative result. The detection limit of the multiplex PCR in soil samples artificially spiked with known quantities of B. pseudomallei and B. thailandensis were 5 and 6 CFU/g soil, respectively. Furthermore, comparison between standard bacterial culture and the multiplex PCR to detect B. pseudomallei from 34 soil samples, collected from an endemic area of melioidosis, showed high sensitivity and specificity. This robust, sensitive, and specific PCR assay will be a useful tool for epidemiological study of B. pseudomallei and closely related members with pathogenic potential in soil.
Topics: Burkholderia; DNA Barcoding, Taxonomic; Microbiota; Polymerase Chain Reaction; Soil Microbiology
PubMed: 33411797
DOI: 10.1371/journal.pone.0245175 -
Antimicrobial Agents and Chemotherapy Oct 2021The Burkholderia cepacia complex (Bcc) and Burkholderia gladioli are opportunistic pathogens that most commonly infect persons with cystic fibrosis or compromised immune...
The Burkholderia cepacia complex (Bcc) and Burkholderia gladioli are opportunistic pathogens that most commonly infect persons with cystic fibrosis or compromised immune systems. Members of the genus are intrinsically multidrug resistant (MDR), possessing both a PenA carbapenemase and an AmpC β-lactamase, rendering treatment of infections due to these species problematic. Here, we tested the β-lactam-β-lactamase inhibitor combination imipenem-relebactam against a panel of MDR Bcc and B. gladioli strains. The addition of relebactam to imipenem dramatically lowered the MICs for Bcc and B. gladioli: only 16% of isolates tested susceptible to imipenem, while 71.3% were susceptible to the imipenem-relebactam combination. While ceftazidime-avibactam remained the most potent combination drug against this panel of Bcc and B. gladioli strains, imipenem-relebactam was active against 71.4% of the ceftazidime-avibactam-resistant isolates. Relebactam demonstrated potent inactivation of Burkholderia multivorans PenA1, with an apparent () value of 3.2 μM. Timed mass spectrometry revealed that PenA1 formed a very stable adduct with relebactam, without any detectable desulfation for as long as 24 h. Based on our results, imipenem-relebactam may represent an alternative salvage therapy for Bcc and B. gladioli infections, especially in cases where the isolates are resistant to ceftazidime-avibactam.
Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Burkholderia; Burkholderia cepacia complex; Burkholderia gladioli; Drug Resistance, Multiple, Bacterial; Imipenem; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 34370574
DOI: 10.1128/AAC.01332-21 -
FEMS Microbiology Reviews Jul 2008Both in natural and in managed ecosystems, bacteria are common inhabitants of the phytosphere and the internal tissues of plants. Probably the most diverse and... (Review)
Review
Both in natural and in managed ecosystems, bacteria are common inhabitants of the phytosphere and the internal tissues of plants. Probably the most diverse and environmentally adaptable plant-associated bacteria belong to the genus Burkholderia. This genus is well-known for its human, animal and plant pathogenic members, including the Burkholderia cepacia complex. However, it also contains species and strains that are beneficial to plants and can be potentially exploited in biotechnological processes. Here we present an overview of plant-associated Burkholderia spp. with special emphasis on beneficial plant-Burkholderia interactions. A discussion of the potential for utilization of stable plant-Burkholderia spp. associations in the development of low-input cropping systems is also provided.
Topics: Animals; Antibiosis; Biodiversity; Burkholderia; Fungi; Insecta; Plant Development; Plant Diseases; Plant Physiological Phenomena; Plant Roots; Plants; Soil Microbiology; Symbiosis
PubMed: 18422616
DOI: 10.1111/j.1574-6976.2008.00113.x -
Genetic and phenotypic diversity in Burkholderia: contributions by prophage and phage-like elements.BMC Microbiology Jul 2010Burkholderia species exhibit enormous phenotypic diversity, ranging from the nonpathogenic, soil- and water-inhabiting Burkholderia thailandensis to the virulent,...
BACKGROUND
Burkholderia species exhibit enormous phenotypic diversity, ranging from the nonpathogenic, soil- and water-inhabiting Burkholderia thailandensis to the virulent, host-adapted mammalian pathogen B. mallei. Genomic diversity is evident within Burkholderia species as well. Individual isolates of Burkholderia pseudomallei and B. thailandensis, for example, carry a variety of strain-specific genomic islands (GIs), including putative pathogenicity and metabolic islands, prophage-like islands, and prophages. These GIs may provide some strains with a competitive advantage in the environment and/or in the host relative to other strains.
RESULTS
Here we present the results of analysis of 37 prophages, putative prophages, and prophage-like elements from six different Burkholderia species. Five of these were spontaneously induced to form bacteriophage particles from B. pseudomallei and B. thailandensis strains and were isolated and fully sequenced; 24 were computationally predicted in sequenced Burkholderia genomes; and eight are previously characterized prophages or prophage-like elements. The results reveal numerous differences in both genome structure and gene content among elements derived from different species as well as from strains within species, due in part to the incorporation of additional DNA, or 'morons' into the prophage genomes. Implications for pathogenicity are also discussed. Lastly, RNAseq analysis of gene expression showed that many of the genes in varphi1026b that appear to contribute to phage and lysogen fitness were expressed independently of the phage structural and replication genes.
CONCLUSIONS
This study provides the first estimate of the relative contribution of prophages to the vast phenotypic diversity found among the Burkholderiae.
Topics: Bacteriophages; Burkholderia; Genetic Variation; Genome, Bacterial; Genome, Viral; Host-Pathogen Interactions; Molecular Sequence Data; Phylogeny; Prophages; Species Specificity
PubMed: 20667135
DOI: 10.1186/1471-2180-10-202