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Drug Resistance Updates : Reviews and... Sep 2016The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus... (Review)
Review
The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. The first line of defense against antimicrobials in Burkholderia species is the outer membrane penetration barrier. Most Burkholderia contain a modified lipopolysaccharide that causes intrinsic polymyxin resistance. Contributing to reduced drug penetration are restrictive porin proteins. Efflux pumps of the resistance nodulation cell division family are major players in Burkholderia multidrug resistance. Third and fourth generation β-lactam antibiotics are seminal for treatment of Burkholderia infections, but therapeutic efficacy is compromised by expression of several β-lactamases and ceftazidime target mutations. Altered DNA gyrase and dihydrofolate reductase targets cause fluoroquinolone and trimethoprim resistance, respectively. Although antibiotic resistance hampers therapy of Burkholderia infections, the characterization of resistance mechanisms lags behind other non-enteric Gram-negative pathogens, especially ESKAPE bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Burkholderia; Burkholderia Infections; Burkholderia mallei; Burkholderia pseudomallei; DNA Gyrase; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Genes, MDR; Glanders; Horses; Humans; Melioidosis; Porins; Tetrahydrofolate Dehydrogenase
PubMed: 27620956
DOI: 10.1016/j.drup.2016.07.003 -
Cells Dec 2020The genus includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are , , and... (Review)
Review
The genus includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are , , and the members of the complex (Bcc). and , the cause of glanders and melioidosis, respectively, are considered potential bioweapons. The Bcc comprises a subset of species associated with respiratory infections in people with chronic granulomatous disease and cystic fibrosis. Antimicrobial treatment of infections is difficult due to the intrinsic multidrug antibiotic resistance of these bacteria; prophylactic vaccines provide an attractive alternative to counteract these infections. Although commercial vaccines against infections are still unavailable, substantial progress has been made over recent years in the development of vaccines against and . This review critically discusses the current advances in vaccine development against , and the Bcc.
Topics: Animals; Bacterial Vaccines; Burkholderia; Burkholderia Infections; Humans; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit
PubMed: 33322641
DOI: 10.3390/cells9122671 -
Frontiers in Veterinary Science 2022Although glanders has been eradicated in most of the developed world, the disease still persists in various countries such as Brazil, India, Pakistan, Bangladesh, Nepal,... (Review)
Review
Although glanders has been eradicated in most of the developed world, the disease still persists in various countries such as Brazil, India, Pakistan, Bangladesh, Nepal, Iran, Bahrain, UAE and Turkey. It is one of the notifiable diseases listed by the World Organization for Animal Health. Occurrence of glanders imposes restriction on equestrian events and restricts equine movement, thus causing economic losses to equine industry. The genetic diversity and global distribution of the causing agent, (.) , have not been assessed in detail and are complicated by the high clonality of this organism. Among the identification and typing methods, PCR-based methods for distinguishing from its close relative as well as genotyping using tandem repeat regions (MLVA) are established. The advent and continuous advancement of the sequencing techniques and the reconstruction of closed genomes enable the development of genome guided epidemiological tools. For achieving a higher genomic resolution, genotyping methods based on whole genome sequencing data can be employed, like genome-wide single nucleotide polymorphisms. One of the limitations in obtaining complete genomic sequences for further molecular characterization of is its high GC content. In this review, we aim to provide an overview of the widely used detection and typing methods for and illustrate gaps that still require development. The genomic features of , their high homology and clonality will be first described from a comparative genomics perspective. Then, the commonly used molecular detection (PCR systems) and typing systems (e.g., multilocus sequence typing, variable number of tandem repeat analysis) will be presented and put in perspective with recently developed genomic methods. Also, the increasing availability of genomic sequences and evolution of the sequencing methods offers exciting prospects for further refinement of typing, that could overcome the difficulties presently encountered with this particular bacterium.
PubMed: 36452150
DOI: 10.3389/fvets.2022.1056996 -
Current Opinion in Infectious Diseases Jun 2017Burkholderia mallei is a facultative intracellular pathogen that causes the highly contagious and often the fatal disease, glanders. With its high rate of infectivity... (Review)
Review
PURPOSE OF REVIEW
Burkholderia mallei is a facultative intracellular pathogen that causes the highly contagious and often the fatal disease, glanders. With its high rate of infectivity via aerosol and recalcitrance toward antibiotics, this pathogen is considered a potential biological threat agent. This review focuses on the most recent literature highlighting host innate immune response to B. mallei.
RECENT FINDINGS
Recent studies focused on elucidating host innate immune responses to the novel mechanisms and virulence factors employed by B. mallei for survival. Studies suggest that pathogen proteins manipulate various cellular processes, including host ubiquitination pathways, phagosomal escape, and actin-cytoskeleton rearrangement. Immune-signaling molecules such as Toll-like receptors, nucleotode-binding oligomerization domain, myeloid differentiation primary response protein 88, and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-α, play key roles in the induction of innate immune responses. Modifications in B. mallei lipopolysaccharide, in particular, the lipid A acyl groups, stimulate immune responses via Toll-like receptor4 activation that may contribute to persistent infection.
SUMMARY
Mortality is high because of septicemia and immune pathogenesis with B. mallei exposure. An effective innate immune response is critical to controlling the acute phase of the infection. Both vaccination and therapeutic approaches are necessary for complete protection against B. mallei.
Topics: Animals; Burkholderia mallei; Cytokines; Glanders; Humans; Immunity, Innate; Lipopolysaccharides; Toll-Like Receptors; Virulence Factors
PubMed: 28177960
DOI: 10.1097/QCO.0000000000000362 -
Current Protocols in Microbiology May 2017Burkholderia thailandensis is a Gram-negative bacterium endemic to Southeast Asian and northern Australian soils. It is non-pathogenic; therefore, it is commonly used as...
Burkholderia thailandensis is a Gram-negative bacterium endemic to Southeast Asian and northern Australian soils. It is non-pathogenic; therefore, it is commonly used as a model organism for the related human pathogens Burkholderia mallei and Burkholderia pseudomallei. B. thailandensis is relatively easily genetically manipulated and a variety of robust genetic tools can be used in this organism. This unit describes protocols for conjugation, natural transformation, mini-Tn7 insertion, and allelic exchange in B. thailandensis. © 2017 by John Wiley & Sons, Inc.
Topics: Burkholderia; Gene Targeting; Gene Transfer Techniques; Genetics, Microbial; Humans; Mutagenesis, Insertional
PubMed: 28510362
DOI: 10.1002/cpmc.27 -
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 -
Infection, Genetics and Evolution :... Apr 2022Glanders is an infectious zoonosis caused by Burkholderia (B.) mallei that mainly affects equids. The objective of this work was to provide additional knowledge on the...
Glanders is an infectious zoonosis caused by Burkholderia (B.) mallei that mainly affects equids. The objective of this work was to provide additional knowledge on the diversity of the strains circulating in Brazil. Six Burkholderia mallei isolates obtained during necropsies of glanderous horses between 2014 and 2017 in two different states (Pernambuco and Alagoas) were analyzed by polymerase chain reaction-high-resolution melting (PCR-HRM). While four strains (9902 RSC, BM_campo 1, BM_campo 3 and UFAL2) clustered in the L3B2 branch, which already includes the Brazilian 16-2438_BM#8 strain, two strains (BM_campo 2.1 and BM_campo 2.2) clustered within the L3B3sB3 branch, which mostly includes older isolates, from Europe and the Middle East. Whole genome sequencing of two of these strains (UFAL2 and BM_campo 2.1), belonging to different branches, confirmed the HRM typing results and refined the links between the strains, including the description of the L3B3Sb3Gp1SbGp1 genotype, never reported so far for contemporary strains. These results suggest different glanders introduction events in Brazil, including a potential link with strains of European origin, related to colonization or trade.
Topics: Animals; Brazil; Burkholderia mallei; Glanders; Horses; Whole Genome Sequencing; Zoonoses
PubMed: 35183750
DOI: 10.1016/j.meegid.2022.105250 -
Frontiers in Cellular and Infection... 2017is a genus within the β that contains at least 90 validly named species which can be found in a diverse range of environments. A number of pathogenic species occur... (Review)
Review
is a genus within the β that contains at least 90 validly named species which can be found in a diverse range of environments. A number of pathogenic species occur within the genus. These include and , opportunistic pathogens that can infect the lungs of patients with cystic fibrosis, and are members of the complex (Bcc). is also an opportunistic pathogen, but in contrast to Bcc species it causes the tropical human disease melioidosis, while its close relative is the causative agent of glanders in horses. For these pathogens to survive within a host and cause disease they must be able to acquire iron. This chemical element is essential for nearly all living organisms due to its important role in many enzymes and metabolic processes. In the mammalian host, the amount of accessible free iron is negligible due to the low solubility of the metal ion in its higher oxidation state and the tight binding of this element by host proteins such as ferritin and lactoferrin. As with other pathogenic bacteria, species have evolved an array of iron acquisition mechanisms with which to capture iron from the host environment. These mechanisms include the production and utilization of siderophores and the possession of a haem uptake system. Here, we summarize the known mechanisms of iron acquisition in pathogenic species and discuss the evidence for their importance in the context of virulence and the establishment of infection in the host. We have also carried out an extensive bioinformatic analysis to identify which siderophores are produced by each species that is pathogenic to humans.
Topics: Animals; Burkholderia; Burkholderia Infections; Burkholderia gladioli; Burkholderia mallei; Burkholderia pseudomallei; Computational Biology; Cystic Fibrosis; Ferritins; Glanders; Heme; Horses; Humans; Iron; Lactoferrin; Lung; Melioidosis; Siderophores; Virulence
PubMed: 29164069
DOI: 10.3389/fcimb.2017.00460 -
Expert Opinion on Biological Therapy Dec 2019: Two important pathogenic species within the genus , namely () and (), are the causative agents of the life-threatening diseases melioidosis and glanders,... (Review)
Review
: Two important pathogenic species within the genus , namely () and (), are the causative agents of the life-threatening diseases melioidosis and glanders, respectively. Due to their high mortality rate and potential for aerosolization, they have gained interest as potential biothreat agents and are classified as Tier 1 Select Agents.: The manuscript provides an overview of the literature covering the efforts taken in the last 10 years to develop new therapeutics measures against both and , with attention on novel therapeutic agents.: As a result of the complicated antibiotic regimens necessary to treat these infections, development of novel therapeutics is needed to treat both diseases. In recent years, the understanding of the pathogenesis of has improved significantly and so have the efforts to develop novel therapeutic agents with high efficacy, either alone, or in combination with conventional antibiotics.
Topics: Animals; Biological Products; Burkholderia mallei; Burkholderia pseudomallei; Glanders; Humans; Melioidosis
PubMed: 31590578
DOI: 10.1080/14712598.2019.1677602