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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 -
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 -
Vaccine Oct 2017B. pseudomallei is the cause of melioidosis, a serious an often fatal disease of humans and animals. The closely related bacterium B. mallei, which cases glanders, is... (Review)
Review
B. pseudomallei is the cause of melioidosis, a serious an often fatal disease of humans and animals. The closely related bacterium B. mallei, which cases glanders, is considered to be a clonal derivative of B. pseudomallei. Both B. pseudomallei and B. mallei were evaluated by the United States and the former USSR as potential bioweapons. Much of the effort to devise biodefence vaccines in the past decade has been directed towards the identification and formulation of sub-unit vaccines which could protect against both melioidosis and glanders. A wide range of proteins and polysaccharides have been identified which protective immunity in mice. In this review we highlight the significant progress that has been made in developing glycoconjugates as sub-unit vaccines. We also consider some of the important the criteria for licensing, including the suitability of the "animal rule" for assessing vaccine efficacy, the protection required from a vaccine and the how correlates of protection will be identified. Vaccines developed for biodefence purposes could also be used in regions of the world where naturally occurring disease is endemic.
Topics: Animals; Bacterial Vaccines; Burkholderia mallei; Burkholderia pseudomallei; Clinical Trials as Topic; Glanders; Humans; Melioidosis
PubMed: 28336210
DOI: 10.1016/j.vaccine.2017.03.022 -
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 -
Archives of Razi Institute Aug 2023is the main cause of glanders as a dangerous contagious zoonosis disease that is mostly observed in single-hoofed animals, especially horses. Modern molecular...
is the main cause of glanders as a dangerous contagious zoonosis disease that is mostly observed in single-hoofed animals, especially horses. Modern molecular techniques have been recently employed to improve epidemiology for identifying and searching for strains of this bacterium at different times and locations. Due to the unknown number of circulating strains and lack of preventive methods, glanders is still observed in the form of epidemics. The present study aimed to evaluate six field isolates plus two laboratory strains of and using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. All the isolates and strains were microbially cultured in the glycerol nutrient and glycerol agar media. The individually grown colonies of the bacterium were used in the biochemical tests. The DNA of isolates was extracted by boiling, and the PCR-RFLP test was conducted on their genome. Finally, the bacterium was injected into guinea pigs to induce the Straus reaction. The biochemical assays (or bioassays) confirmed the isolates as . The PCR-RFLP assay demonstrated a product for with a length of 650 bp. Nevertheless, 250 and 400 bp were produced for . The swollen scrotum pointed to the occurrence of the Straus reaction. The PCR-RFLP is a proper differential diagnosis technique for ; moreover, it is a suitable method for differentiating between and . This technique can detect in a short time with high precision and sensitivity.
Topics: Horses; Animals; Guinea Pigs; Burkholderia mallei; Glanders; Polymorphism, Restriction Fragment Length; Glycerol; Burkholderia pseudomallei; Polymerase Chain Reaction; Horse Diseases
PubMed: 38226390
DOI: 10.32592/ARI.2023.78.4.1305 -
Frontiers in Cellular and Infection... 2013Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either... (Review)
Review
Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit vaccines have typically provided less robust immunity, but are safer to administer to a wider variety of people, including immune compromised individuals because they do not reactivate or cause disease. The challenges facing B. mallei and B. pseudomalllei vaccine development include identification of broadly protective antigens, design of efficient vaccine delivery and adjuvant systems, and a better understanding of the correlates of protection from both acute and chronic infection.
Topics: Animals; Antigens, Bacterial; Bacterial Vaccines; Burkholderia mallei; Burkholderia pseudomallei; Drug Discovery; Glanders; Humans; Melioidosis; Vaccines, Attenuated; Vaccines, Subunit
PubMed: 23508691
DOI: 10.3389/fcimb.2013.00010 -
FEMS Microbiology Letters Dec 2007Burkholderia mallei, the etiologic agent of the disease known as glanders, is primarily a disease affecting horses and is transmitted to humans by direct contact with... (Review)
Review
Burkholderia mallei, the etiologic agent of the disease known as glanders, is primarily a disease affecting horses and is transmitted to humans by direct contact with infected animals. The use of B. mallei as a biological weapon has been reported and currently, there is no vaccine available for either humans or animals. Despite the history and highly infective nature of B. mallei, as well as its potential use as a bio-weapon, B. mallei research to understand the pathogenesis and the host responses to infection remains limited. Therefore, this minireview will focus on current efforts to elucidate B. mallei virulence, the associated host immune responses elicited during infection and discuss the feasibility of vaccine development.
Topics: Animals; Biological Warfare Agents; Burkholderia mallei; Glanders; Horses; Humans; Virulence
PubMed: 18031330
DOI: 10.1111/j.1574-6968.2007.00949.x -
Military Medicine Jun 2009Burkholderia pseudomallei and mallei are biological agents of military significance. There has been significant research in recent years to develop medical... (Review)
Review
Burkholderia pseudomallei and mallei are biological agents of military significance. There has been significant research in recent years to develop medical countermeasures for these organisms. This review summarizes work which details aspects of the pathogenesis of B. pseudomallei and mallei and discusses key scientific questions and directions for future research.
Topics: Animals; Bacterial Capsules; Bacterial Proteins; Bioterrorism; Burkholderia mallei; Burkholderia pseudomallei; Equidae; Genome, Bacterial; Glanders; Humans; Melioidosis; Quorum Sensing; Virulence
PubMed: 19585782
DOI: No ID Found -
Transboundary and Emerging Diseases Mar 2019Glanders is a highly infectious zoonotic disease caused by Burkholderia mallei. The transmission of B. mallei occurs mainly by direct contact, and horses are the...
Glanders is a highly infectious zoonotic disease caused by Burkholderia mallei. The transmission of B. mallei occurs mainly by direct contact, and horses are the natural reservoir. Therefore, the identification of infection sources within horse populations and animal movements is critical to enhance disease control. Here, we analysed the dynamics of horse movements from 2014 to 2016 using network analysis in order to understand the flow of animals in two hierarchical levels, municipalities and farms. The municipality-level network was used to investigate both community clustering and the balance between the municipality's trades and the farm-level network associations between B. mallei outbreaks and the network centrality measurements, analysed by spatio-temporal generalized additive model (GAM). Causal paths were established for the dispersion of B. mallei outbreaks through the network. Our approach captured and established a direct relationship between movement of infected equines and predicted B. mallei outbreaks. The GAM model revealed that the parameters in degree and closeness centrality out were positively associated with B. mallei. In addition, we also detected 10 communities with high commerce among municipalities. The role of each municipality within the network was detailed, and significant changes in the structures of the network were detected over the course of 3 years. The results suggested the necessity to focus on structural changes of the networks over time to better control glanders disease. The identification of farms with a putative risk of B. mallei infection using the horse movement network provided a direct opportunity for disease control through active surveillance, thus minimizing economic losses and risks for human cases of B. mallei.
Topics: Animals; Brazil; Burkholderia mallei; Disease Outbreaks; Glanders; Horses; Models, Theoretical; Transportation
PubMed: 30427593
DOI: 10.1111/tbed.13071 -
Recent Patents on Anti-infective Drug... Nov 2007Burkholderia mallei and Burkholderia pseudomallei are the causative micro-organisms of Glanders and Melioidosis, respectively. Although now rare in Western countries,... (Review)
Review
Burkholderia mallei and Burkholderia pseudomallei are the causative micro-organisms of Glanders and Melioidosis, respectively. Although now rare in Western countries, both micro-organisms have recently gained much interest because of their unique potential as bioterrorism agents. This paper reviews the epidemiology, pathogenesis, diagnosis and treatment of Melioidosis and Glanders. Recent patents relating to these micro-organisms, especially potential vaccines, are presented. Continued research and development is urgently needed, especially in regard to rapid and accurate diagnosis of melioidosis and glanders, efficacious therapy and primary and secondary prevention.
Topics: Animals; Anti-Bacterial Agents; Bioterrorism; Burkholderia mallei; Burkholderia pseudomallei; Civil Defense; Glanders; Horse Diseases; Horses; Humans; Melioidosis; Patents as Topic
PubMed: 18221181
DOI: 10.2174/157489107782497335