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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 -
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 -
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 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 -
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 -
Journal of the American Veterinary... Aug 2008
Review
Topics: Animals; Bioterrorism; Burkholderia mallei; Disease Outbreaks; Equidae; Glanders; Horses; Humans; Public Health; Species Specificity; Zoonoses
PubMed: 18710311
DOI: 10.2460/javma.233.4.570 -
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 -
PLoS Neglected Tropical Diseases Jan 2023Burkholderia mallei and Burkholderia pseudomallei are both potential biological threat agents. Melioidosis caused by B. pseudomallei is endemic in Southeast Asia and...
BACKGROUND
Burkholderia mallei and Burkholderia pseudomallei are both potential biological threat agents. Melioidosis caused by B. pseudomallei is endemic in Southeast Asia and Northern Australia, while glanders caused by B. mallei infections are rare. Here we studied the proteomes of different B. mallei and B. pseudomallei isolates to determine species specific characteristics.
METHODS
The expressed proteins of 5 B. mallei and 6 B. pseudomallei strains were characterized using liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). Subsequently, expression of potential resistance and virulence related characteristics were analyzed and compared.
RESULTS
Proteome analysis can be used for the identification of B. mallei and B. pseudomallei. Both species were identified based on >60 discriminative peptides. Expression of proteins potentially involved in antimicrobial resistance, AmrAB-OprA, BpeAB-OprB, BpeEF-OprC, PenA as well as several other efflux pump related proteins and putative β-lactamases was demonstrated. Despite, the fact that efflux pump BpeAB-OprB was expressed in all isolates, no clear correlation with an antimicrobial phenotype and the efflux-pump could be established. Also consistent with the phenotypes, no amino acid mutations in PenA known to result in β-lactam resistance could be identified. In all studied isolates, the expression of virulence (related) factors Capsule-1 and T2SS was demonstrated. The expression of T6SS-1 was demonstrated in all 6 B. pseudomallei isolates and in 2 of the 5 B. mallei isolates. In all, except one B. pseudomallei isolate, poly-beta-1,6 N-acetyl-D-glucosamine export porin (Pga), important for biofilm formation, was detected, which were absent in the proteomes of B. mallei. Siderophores, iron binding proteins, malleobactin and malleilactone are possibly expressed in both species under standard laboratory growth conditions. Expression of multiple proteins from both the malleobactin and malleilactone polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) clusters was demonstrated in both species. All B. pseudomallei expressed at least seven of the nine proteins of the bactobolin synthase cluster (bactobolin, is a ribosome targeting antibiotic), while only in one B. mallei isolate expression of two proteins of this synthase cluster was identified.
CONCLUSIONS
Analyzing the expressed proteomes revealed differences between B. mallei and B. pseudomallei but also between isolates from the same species. Proteome analysis can be used not only to identify B. mallei and B. pseudomallei but also to characterize the presence of important factors that putatively contribute to the pathogenesis of B. mallei and B. pseudomallei.
Topics: Animals; Burkholderia pseudomallei; Burkholderia mallei; Proteome; Virulence; Anti-Bacterial Agents; Melioidosis
PubMed: 36607891
DOI: 10.1371/journal.pntd.0011006