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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 -
Journal of Family Medicine and Primary... Sep 2022Melioidosis is a complex tropical disease linked with many complications. It is increasingly diagnosed in India. The clinical mimicry of this disease with several other... (Review)
Review
Melioidosis is a complex tropical disease linked with many complications. It is increasingly diagnosed in India. The clinical mimicry of this disease with several other common causes of pneumonia has kept the clinicians in ignorance. Usually, the diagnosis and appropriate management get delayed. The organism closely resembles the common contaminant Pseudomonas and is easily misidentified in microbiology laboratories. The diagnosis is often missed because of poor diagnostic sensitivity of blood culture, the gold standard of the diagnosis. All this contributes to increased morbidity and mortality. The rampant use of high-end broad-spectrum antibiotics like ceftazidime and meropenem at suboptimal dose and duration suppresses the diagnosis without eradicating the disease, leaving the chance of recurrence from its latency even after years. As an infectious disease, the cure and prevention depend on early diagnosis and treatment. An awareness of its peculiar presentations and history can differentiate clinically and suspect the condition much easily from other mimickers of tuberculosis to sepsis. Ultimately, the prevention of melioidosis remains the critical strategy. Increasing the number of cases and intricated management of this fatal but potentially curable disease had prompted us to take up the mission of preventing the disease by spreading knowledge and awareness.
PubMed: 36505663
DOI: 10.4103/jfmpc.jfmpc_1_22 -
Clinical Medicine (London, England) Jan 2022Melioidosis is an infectious disease with high mortality and a wide spectrum of clinical manifestations. Successful treatment requires lengthy antibiotic regimens,...
Melioidosis is an infectious disease with high mortality and a wide spectrum of clinical manifestations. Successful treatment requires lengthy antibiotic regimens, making microbiological diagnosis crucial. In this article, we briefly review the diagnosis and management of melioidosis from the clinician's viewpoint.
Topics: Anti-Bacterial Agents; Burkholderia pseudomallei; Humans; Melioidosis
PubMed: 35078788
DOI: 10.7861/clinmed.2022-0014 -
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 -
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 -
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 -
Microorganisms Mar 2021Melioidosis is a severe disease caused by (), a Gram-negative environmental bacterium. It is endemic in Southeast Asia and Northern Australia, but it is underreported... (Review)
Review
Melioidosis is a severe disease caused by (), a Gram-negative environmental bacterium. It is endemic in Southeast Asia and Northern Australia, but it is underreported in many other countries. The principal routes of entry for are skin penetration, inhalation, and ingestion. It mainly affects immunocompromised populations, especially patients with type 2 diabetes mellitus. The laboratory diagnosis of melioidosis is challenging due to its non-specific clinical manifestations, which mimic other severe infections. The culture method is considered an imperfect gold standard for the diagnosis of melioidosis due to its low sensitivity. Antibody detection has low sensitivity and specificity due to the high seropositivity among healthy people in endemic regions. Antigen detection using various proteins has been tested for the rapid determination of ; however, it presents certain limitations in terms of its sensitivity and specificity. Therefore, this review aims to frame the present knowledge of a potential target known as the invasion protein D (BipD), including future directions for its detection using an aptamer-based sensor (aptasensor).
PubMed: 33808203
DOI: 10.3390/microorganisms9040711 -
Pathogens (Basel, Switzerland) Oct 2021Significant advancement has been made in the development of vaccines against bacterial pathogens. However, several roadblocks have been found during the evaluation of... (Review)
Review
Significant advancement has been made in the development of vaccines against bacterial pathogens. However, several roadblocks have been found during the evaluation of vaccines against intracellular bacterial pathogens. Therefore, new lessons could be learned from different vaccines developed against unrelated intracellular pathogens. Bacillary dysentery and melioidosis are important causes of morbidity and mortality in developing nations, which are caused by the intracellular bacteria and , respectively. Although the mechanisms of bacterial infection, dissemination, and route of infection do not provide clues about the commonalities of the pathogenic infectious processes of these bacteria, a wide variety of vaccine platforms recently evaluated suggest that in addition to the stimulation of antibodies, identifying protective antigens and inducing T cell responses are some additional required elements to induce effective protection. In this review, we perform a comparative evaluation of recent candidate vaccines used to combat these two infectious agents, emphasizing the common strategies that can help investigators advance effective and protective vaccines to clinical trials.
PubMed: 34832508
DOI: 10.3390/pathogens10111353