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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 -
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 -
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 -
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 -
Applied Microbiology and Biotechnology Dec 2021Bacteria belonging to the Burkholderia genus are extremely versatile and diverse. They can be environmental isolates, opportunistic pathogens in cystic fibrosis,... (Review)
Review
Bacteria belonging to the Burkholderia genus are extremely versatile and diverse. They can be environmental isolates, opportunistic pathogens in cystic fibrosis, immunocompromised or chronic granulomatous disease patients, or cause disease in healthy people (e.g., Burkholderia pseudomallei) or animals (as in the case of Burkholderia mallei). Since the genus was separated from the Pseudomonas one in the 1990s, the methodological tools to study and characterize these bacteria are evolving fast. Here we reviewed the techniques used in the last few years to update the taxonomy of the genus, to study gene functions and regulations, to deepen the knowledge on the drug resistance which characterizes these bacteria, and to elucidate their mechanisms to establish infections. The availability of these tools significantly impacts the quality of research on Burkholderia and the choice of the most appropriated is fundamental for a precise characterization of the species of interest.Key points• Updated techniques to study the genus Burkholderia were reviewed.• Taxonomy, genomics, assays, and animal models were described.• A comprehensive overview on recent advances in Burkholderia studies was made.
Topics: Animals; Burkholderia; Burkholderia Infections; Burkholderia mallei; Burkholderia pseudomallei; Cystic Fibrosis; Humans
PubMed: 34755214
DOI: 10.1007/s00253-021-11667-3 -
Frontiers in Veterinary Science 2022The One Health concept was initiated to promote the integration of human, animal, and environmental ecosystems into healthcare to ensure effective control and the... (Review)
Review
The One Health concept was initiated to promote the integration of human, animal, and environmental ecosystems into healthcare to ensure effective control and the sustainable governance of multifaceted health matters. Climate change, deforestation, and rigorous farming disrupt the environment, which serves as the natural habitat for many animals and microbes, increasing the likelihood of disease transmission between humans and animals. Melioidosis (neglected tropical diseases) and glanders are of humans and animals caused by the gram-negative bacteria and its close relative , respectively. In Malaysia, although melioidosis is endemic, it is not a notifiable disease. Hence, the true prevalence of melioidosis in Malaysia is unknown and varies in different regions of the country, with reported hotspots associated with agriculture-related activities. To date, no incidence of human glanders has been reported in Malaysia, although occupational exposure for equine handlers and veterinary professionals remains a concern. Additionally, antibiotics are widely used in the healthcare and veterinary sectors to treat or prevent and infections, leading to the emergence of resistance in . Lack of surveillance, research, assessment, and management of glanders and melioidosis is a major issue in Malaysia. Proper assessment systems and cross-discipline cooperation are vital to recognize and manage both diseases. Experts and practitioners from clinical and veterinary disciplines, environmentalists, law enforcement, policymakers, researchers, local communities, and other experts need to communicate, collaborate, and coordinate activities to fill the knowledge gap on glanders and melioidosis to reduce morbidity and mortality rates in the country. This review aims to define the organizational and functional characteristics of One Health surveillance approaches for glanders and melioidosis from a Malaysian perspective.
PubMed: 36590813
DOI: 10.3389/fvets.2022.1056723 -
PloS One 2022Burkholderia mallei is the etiological agent of glanders, a highly contagious and often fatal disease in equids. Due to the high genetic clonality of B. mallei,...
Burkholderia mallei is the etiological agent of glanders, a highly contagious and often fatal disease in equids. Due to the high genetic clonality of B. mallei, high-resolution typing assays are necessary to differentiate between individual strains. Here we report on the development and validation of a robust and reproducible core genome-based Multi Locus Sequence Typing Assay (cgMLST) for B. mallei, which is based on 3328 gene targets and enables high-resolution typing at the strain level. The assay was validated using a set of 120 B. mallei genomes from public databases and 23 newly sequenced outbreak strains from in-house strain collections. In this cgMLST analysis, strains from different geographic regions were clearly distinguished by at least 70 allele differences, allowing spatial clustering while closely related and epidemiologically related strains were separated by only zero to three alleles. Neither the different sequencing technologies nor the assembly strategies had an influence on the cgMLST results. The developed cgMLST is highly robust, reproducible and can be used for outbreak investigations, source tracking and molecular characterization of new B. mallei isolates.
Topics: Animals; Burkholderia mallei; Genetic Variation; Genome, Bacterial; Genotype; Multilocus Sequence Typing
PubMed: 35793321
DOI: 10.1371/journal.pone.0270499 -
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