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Australian Journal of General Practice May 2019Endemic to soils of Northern Australia, Burkholderia pseudomallei is the Gram-negative pathogen responsible for melioidosis, which causes a clinical spectrum ranging... (Review)
Review
BACKGROUND
Endemic to soils of Northern Australia, Burkholderia pseudomallei is the Gram-negative pathogen responsible for melioidosis, which causes a clinical spectrum ranging from pneumonia and/or cutaneous infection to disseminated disease with fulminant septicaemia. Incident cases peak after monsoonal rains, particularly in individuals with immune dysfunction. Early diagnosis of melioidosis is challenging for clinicians, given its ability to mimic many other diseases and high clinical (associated mortality) impact.
OBJECTIVES
The aim of this paper is to provide general practitioners with an overview of melioidosis, covering epidemiology, risk factors for infection, clinical disease spectrum, diagnostic techniques and an approach to management, including public health aspects.
DISCUSSION
Primary care physicians play a key role in early disease recognition, initial patient stabilisation, request of appropriate clinical samples (particularly blood cultures) and prompt commencement of efficacious antibiotics. Patient education is paramount during high-risk periods, chiefly for patients with diabetes and/or those who engage in hazardous alcohol use, living in endemic areas of Australia.
Topics: Adult; Anti-Bacterial Agents; Australia; Burkholderia pseudomallei; Female; Humans; Male; Melioidosis; Middle Aged; Risk Factors
PubMed: 31129946
DOI: 10.31128/AJGP-04-18-4558 -
Clinical Microbiology Reviews Mar 2020The causative agent of melioidosis, , a tier 1 select agent, is endemic in Southeast Asia and northern Australia, with increased incidence associated with high levels of... (Review)
Review
The causative agent of melioidosis, , a tier 1 select agent, is endemic in Southeast Asia and northern Australia, with increased incidence associated with high levels of rainfall. Increasing reports of this condition have occurred worldwide, with estimates of up to 165,000 cases and 89,000 deaths per year. The ecological niche of the organism has yet to be clearly defined, although the organism is associated with soil and water. The culture of appropriate clinical material remains the mainstay of laboratory diagnosis. Identification is best done by phenotypic methods, although mass spectrometric methods have been described. Serology has a limited diagnostic role. Direct molecular and antigen detection methods have limited availability and sensitivity. Clinical presentations of melioidosis range from acute bacteremic pneumonia to disseminated visceral abscesses and localized infections. Transmission is by direct inoculation, inhalation, or ingestion. Risk factors for melioidosis include male sex, diabetes mellitus, alcohol abuse, and immunosuppression. The organism is well adapted to intracellular survival, with numerous virulence mechanisms. Immunity likely requires innate and adaptive responses. The principles of management of this condition are drainage and debridement of infected material and appropriate antimicrobial therapy. Global mortality rates vary between 9% and 70%. Research into vaccine development is ongoing.
Topics: Africa; Americas; Animals; Anti-Bacterial Agents; Asia, Southeastern; Bacteremia; Burkholderia pseudomallei; Humans; Melioidosis; Microbiological Techniques; Molecular Diagnostic Techniques; Oceania; Risk Factors; Virulence
PubMed: 32161067
DOI: 10.1128/CMR.00006-19 -
Trends in Microbiology Jan 2024is a Gram negative, facultative intracellular bacterium that resides in the rhizosphere of tropical soils. causes melioidosis, which is transmitted by cutaneous entry,...
is a Gram negative, facultative intracellular bacterium that resides in the rhizosphere of tropical soils. causes melioidosis, which is transmitted by cutaneous entry, ingestion, or inhalation of contaminated soil or water. Infection with can cause a wide array of clinical symptoms such as pneumonia, bone, joint, skin, genitourinary, and central nervous system infections, as well as parotid abscesses in children. Mammalian virulence is linked to the intracellular life cycle, which begins with attachment and internalization by host cells. can infect a wide range of eukaryotic cells, including macrophages, monocytes, and neutrophils, as well as nonphagocytic cells. Once internalized, a type 3 secretion system (T3SS) facilitates escape from the phagosome, and the bacteria replicate in the cytoplasm. Autotransporter protein BimA mediates actin polymerization, enabling to spread, cell to cell, using actin-based motility. This process, coupled with the activity of a type 6 secretion system (T6SS-5), results in host membrane fusion and the formation of multinucleated giant cells. Capsule polysaccharides also contribute to virulence and evasion of host innate immunity. Treatment of infections is complicated by the organism’s intrinsic resistance to multiple classes of antimicrobials, largely due to an abundance of efflux pumps and reduced outer membrane permeability. While is commonly associated with endemic ‘hotspots’ in southeast Asia and northern Australia, there is increasing evidence that it is likely endemic in a large range of tropical and subtropical areas, including regions in Africa, South America, the Middle East, Central America, and the Caribbean. Soil and climate conditions favorable for survival are also found in additional areas worldwide. Consequently, it is important for clinical and public health laboratories located outside of high-endemicity areas to be aware of , as well as for improved diagnostic and reporting methods.
Topics: Burkholderia pseudomallei; Burkholderia
PubMed: 37634974
DOI: 10.1016/j.tim.2023.07.008 -
PloS One 2021Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form...
Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form small colony variants (SCVs) as part of the adaptive features in response to environmental stress. In this study, we characterize the genomic characteristics, antimicrobial resistance (AMR), and metabolic phenotypes of B. pseudomallei SCV and wild type (WT) strains. Whole-genome sequence analysis was performed to characterize the genomic features of two SCVs (CS and OS) and their respective parental WT strains (CB and OB). Phylogenetic relationship between the four draft genomes in this study and 19 publicly available genomes from various countries was determined. The four draft genomes showed a close phylogenetic relationship with other genomes from Southeast Asia. Broth microdilution and phenotype microarray were conducted to determine the AMR profiles and metabolic features (carbon utilization, osmolytes sensitivity, and pH conditions) of all strains. The SCV strains exhibited identical AMR phenotype with their parental WT strains. A limited number of AMR-conferring genes were identified in the B. pseudomallei genomes. The SCVs and their respective parental WT strains generally shared similar carbon-utilization profiles, except for D,L-carnitine (CS), g-hydroxybutyric acid (OS), and succinamic acid (OS) which were utilized by the SCVs only. No difference was observed in the osmolytes sensitivity of all strains. In comparison, WT strains were more resistant to alkaline condition, while SCVs showed variable growth responses at higher acidity. Overall, the genomes of the colony morphology variants of B. pseudomallei were largely identical, and the phenotypic variations observed among the different morphotypes were strain-specific.
Topics: Adaptation, Biological; Burkholderia pseudomallei; Drug Resistance, Microbial; Genomics; Genotype; Phenotype; Phylogeny; Exome Sequencing
PubMed: 34910764
DOI: 10.1371/journal.pone.0261382 -
BioMed Research International 2018is a Gram-negative bacterium that causes melioidosis, which can be fatal in humans. Melioidosis is prevalent in the tropical regions of Southeast Asia and Northern... (Review)
Review
is a Gram-negative bacterium that causes melioidosis, which can be fatal in humans. Melioidosis is prevalent in the tropical regions of Southeast Asia and Northern Australia. Ecological data have shown that this bacterium can survive as a free-living organism in environmental niches, such as soil and water, as well as a parasite living in host organisms, such as ameba, plants, fungi, and animals. This review provides an overview of the survival and adaptation of to stressful conditions induced by hostile environmental factors, such as salinity, oxidation, and iron levels. The adaptation of in host cells is also reviewed. The adaptive survival mechanisms of this pathogen mainly involve modulation of gene and protein expression, which could cause alterations in the bacteria's cell membrane, metabolism, and virulence. Understanding the adaptations of this organism to environmental factors provides important insights into the survival and pathogenesis of , which may lead to the development of novel strategies for the control, prevention, and treatment of melioidosis in the future.
Topics: Adaptation, Physiological; Animals; Asia, Southeastern; Australia; Burkholderia pseudomallei; Humans; Melioidosis; Virulence
PubMed: 29992136
DOI: 10.1155/2018/3039106 -
BMC Microbiology May 2021Burkholderia pseudomallei, a facultative intracellular bacterium, is the aetiological agent of melioidosis that is responsible for up to 40% sepsis-related mortality in...
BACKGROUND
Burkholderia pseudomallei, a facultative intracellular bacterium, is the aetiological agent of melioidosis that is responsible for up to 40% sepsis-related mortality in epidemic areas. However, no effective vaccine is available currently, and the drug resistance is also a major problem in the treatment of melioidosis. Therefore, finding new clinical treatment strategies in melioidosis is extremely urgent.
RESULTS
We demonstrated that tauroursodeoxycholic acid (TUDCA), a clinically available endoplasmic reticulum (ER) stress inhibitor, can promote B. pseudomallei clearance both in vivo and in vitro. In this study, we investigated the effects of TUDCA on the survival of melioidosis mice, and found that treatment with TUDCA significantly decreased intracellular survival of B. pseudomallei. Mechanistically, we found that B. pseudomallei induced apoptosis and activated IRE1 and PERK signaling ways of ER stress in RAW264.7 macrophages. TUDCA treatment could reduce B. pseudomallei-induced ER stress in vitro, and TUDCA is protective in vivo.
CONCLUSION
Taken together, our study has demonstrated that B. pseudomallei infection results in ER stress-induced apoptosis, and TUDCA enhances the clearance of B. pseudomallei by inhibiting ER stress-induced apoptosis both in vivo and in vitro, suggesting that TUDCA could be used as a potentially alternative treatment for melioidosis.
Topics: Animals; Apoptosis; Burkholderia pseudomallei; Cell Line; Endoplasmic Reticulum Stress; Melioidosis; Mice; Signal Transduction; Survival Analysis; Taurochenodeoxycholic Acid
PubMed: 33947331
DOI: 10.1186/s12866-021-02199-x -
The American Journal of Tropical... Feb 2021Melioidosis, caused by Burkholderia pseudomallei, is increasingly recognized in several regions of the globe. The present study was performed to identify and determine...
Melioidosis, caused by Burkholderia pseudomallei, is increasingly recognized in several regions of the globe. The present study was performed to identify and determine the frequency of B. pseudomallei infection in localized pyogenic lesions in eastern India and describe their clinico-microbiological profile. Pus samples were subjected to standard microbiological techniques for isolation and identification of various bacteria, including B. pseudomallei, which were confirmed by PCR. The clinical and demographic details of patients with melioidosis and antimicrobial susceptibility pattern of B. pseudomallei isolates were analyzed. Of 245 samples, 126 (51.4%) were culture positive, yielding 137 isolates. Staphylococcus aureus was the predominant pathogen accounting for 54 (39.4%) isolates, followed by B. pseudomallei accounting for 34 (24.8%) isolates. The mean age of the patients with melioidosis was 39.1 years, with males (24/34; 70.6%) being affected more than females (10/34; 29.4%). A majority of the patients were laborers (12/34; 35.3), followed by homemakers (8/34; 23.5%). Head and neck abscesses (35.3%) were the most common presentation followed by pyogenic lesions of the musculoskeletal system (32.3%) and deep organ abscesses (23.5%). Clinical resolution of infection was observed in 31 (91.2%) patients, relapse in two (5.9%) patients, and death in one (2.9%) patient, respectively. Susceptibility testing revealed all B. pseudomallei isolates to be completely susceptible to the following antimicrobials: ceftazidime, trimethoprim-sulfamethoxazole, imipenem, and doxycycline, with one (2.9%) resistant to amoxicillin-clavulanic acid. Burkholderia pseudomallei is an emerging etiological agent of localized pyogenic infections in eastern India, affecting a mainly adult male population. An increased vigilance along with appropriate diagnostic techniques helps in accurate diagnosis facilitating appropriate therapy.
Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Burkholderia pseudomallei; Child; Female; Humans; India; Male; Melioidosis; Microbial Sensitivity Tests; Middle Aged; Tertiary Healthcare; Young Adult
PubMed: 33534740
DOI: 10.4269/ajtmh.20-1386 -
Microbial Genomics Apr 2023, a Gram-negative pathogen, is the causative agent of melioidosis in humans. This bacterium can be isolated from the soil, stagnant and salt-water bodies, and human and...
, a Gram-negative pathogen, is the causative agent of melioidosis in humans. This bacterium can be isolated from the soil, stagnant and salt-water bodies, and human and animal clinical specimens. While extensive studies have contributed to our understanding of pathogenesis, little is known about how a harmless soil bacterium adapts when it shifts to a human host and exhibits its virulence. The bacterium's large genome encodes an array of factors that support the pathogen's ability to survive under stressful conditions, including the host's internal milieu. In this study, we performed comparative transcriptome analysis of cultured in human plasma versus soil extract media to provide insights into gene expression that governs bacterial adaptation and infectivity in the host. A total of 455 genes were differentially regulated; genes upregulated in grown in human plasma are involved in energy metabolism and cellular processes, whilst the downregulated genes mostly include fatty acid and phospholipid metabolism, amino acid biosynthesis and regulatory function proteins. Further analysis identified a significant upregulation of biofilm-related genes in plasma, which was validated using the biofilm-forming assay and scanning electron microscopy. In addition, genes encoding known virulence factors such as capsular polysaccharide and flagella were also overexpressed, suggesting an overall enhancement of virulence potential when present in human plasma. This gene expression profile provides comprehensive information on 's adaptation when shifted from the environment to the host. The induction of biofilm formation under host conditions may explain the difficulty in treating septic melioidosis.
Topics: Animals; Humans; Burkholderia pseudomallei; Melioidosis; Adaptation, Physiological; Virulence; Virulence Factors
PubMed: 37018040
DOI: 10.1099/mgen.0.000982 -
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 -
Nature Communications Mar 2021Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations, which has hampered further...
Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations, which has hampered further understanding of spatiotemporal and stage-specific processes of prokaryotic cells within complex environments. Here we develop a 'TRANSITomic' approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection at defined stages, yielding pathophysiological insights. We find that B. pseudomallei transits through host cells during infection in three observable stages: vacuole entry; cytoplasmic escape and replication; and membrane protrusion, promoting cell-to-cell spread. The B. pseudomallei 'TRANSITome' reveals dynamic gene-expression flux during transit in host cells and identifies genes that are required for pathogenesis. We find several hypothetical proteins and assign them to virulence mechanisms, including attachment, cytoskeletal modulation, and autophagy evasion. The B. pseudomallei 'TRANSITome' provides prokaryotic single-cell transcriptomics information enabling high-resolution understanding of host-pathogen interactions.
Topics: Animals; Bacterial Proteins; Burkholderia pseudomallei; Cell Line, Tumor; Cell Membrane; Computational Biology; Cytoplasm; Gene Expression Profiling; Genes, Bacterial; HEK293 Cells; Host-Pathogen Interactions; Humans; Melioidosis; Mice; Mice, Inbred BALB C; RAW 264.7 Cells; Single-Cell Analysis; Vacuoles; Virulence; Virulence Factors
PubMed: 33772012
DOI: 10.1038/s41467-021-22169-1