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Nature Reviews. Disease Primers Feb 2018Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account... (Review)
Review
Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.
Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Burkholderia pseudomallei; Ceftazidime; Disease Eradication; Global Burden of Disease; Humans; Imipenem; Immunotherapy, Active; Melioidosis; Meropenem; Risk Factors
PubMed: 29388572
DOI: 10.1038/nrdp.2017.107 -
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 -
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 -
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 -
Emerging Infectious Diseases Jan 2018In contrast with northern Australia and Thailand, in Singapore the incidence of melioidosis and co-incidence of melioidosis and pneumonia have declined. Burkholderia...
In contrast with northern Australia and Thailand, in Singapore the incidence of melioidosis and co-incidence of melioidosis and pneumonia have declined. Burkholderia pseudomallei deep abscesses increased 20.4% during 2003-2014. These trends could not be explained by the environmental and climatic factors conventionally ascribed to melioidosis.
Topics: Adult; Aged; Aged, 80 and over; Burkholderia pseudomallei; Climate; Environment; Female; Humans; Incidence; Male; Melioidosis; Middle Aged; Singapore; Young Adult
PubMed: 29260679
DOI: 10.3201/eid2401.161449 -
Virulence Dec 2022The soil saprophyte, , is the causative agent of melioidosis, a disease endemic in South East Asia and northern Australia. Exposure to by either inhalation or... (Review)
Review
The soil saprophyte, , is the causative agent of melioidosis, a disease endemic in South East Asia and northern Australia. Exposure to by either inhalation or inoculation can lead to severe disease. rapidly shifts from an environmental organism to an aggressive intracellular pathogen capable of rapidly spreading around the body. The expression of multiple virulence factors at every stage of intracellular infection allows for rapid progression of infection. Following invasion or phagocytosis, resists host-cell killing mechanisms in the phagosome, followed by escape using the type III secretion system. Several secreted virulence factors manipulate the host cell, while bacterial cells undergo a shift in energy metabolism allowing for overwhelming intracellular replication. Polymerisation of host cell actin into "actin tails" propels to the membranes of host cells where the type VI secretion system fuses host cells into multinucleated giant cells (MNGCs) to facilitate cell-to-cell dissemination. This review describes the various mechanisms used by to survive within cells.
Topics: Humans; Burkholderia pseudomallei; Virulence; Actins; Melioidosis; Virulence Factors
PubMed: 36271712
DOI: 10.1080/21505594.2022.2139063 -
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 -
The Indian Journal of Medical Research Apr 2019
Topics: Burkholderia pseudomallei; Female; Gram-Negative Bacteria; Humans; Liver; Magnetic Resonance Imaging; Melioidosis; Spleen; Young Adult
PubMed: 31411183
DOI: 10.4103/ijmr.IJMR_2018_17 -
Emerging Infectious Diseases Mar 2021We report a case of melioidosis in China and offer a comparison of 5 commercial detection systems for Burkholderia pseudomallei. The organism was misidentified by the...
We report a case of melioidosis in China and offer a comparison of 5 commercial detection systems for Burkholderia pseudomallei. The organism was misidentified by the VITEK 2 Compact, Phoenix, VITEK mass spectrometry, and API 20NE systems but was eventually identified by the Bruker Biotyper system and 16S rRNA sequencing.
Topics: Burkholderia pseudomallei; China; Humans; Melioidosis; RNA, Ribosomal, 16S; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 33622484
DOI: 10.3201/eid2703.191769