Burkholderia pseudomallei

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Burkholderia pseudomallei
Bps close.JPG
B. pseudomallei colonies on Ashdown's agar showing the characteristic cornflower head morphology
Scientific classification
B. pseudomallei
Binomial name
Burkholderia pseudomallei
(Whitmore 1913)
Yabuuchi et al. 1993 [1]

Bacillus pseudomallei Whitmore 1913
Bacterium whitmoriStanton and Fletcher 1921
Malleomyces pseudomalleiBreed 1939
Loefflerella pseudomalleiBrindle and Cowan 1951
Pfeiferella pseudomallei
Pseudomonas pseudomallei(Whitmore 1913) Haynes 1957


Burkholderia pseudomallei (also known as Pseudomonas pseudomallei) is a Gram-negative, bipolar, aerobic, motile rod-shaped bacterium. [2] It is a soil-dwelling bacterium endemic in tropical and subtropical regions worldwide, particularly in Thailand and northern Australia. [3] It infects humans and animals and causes the disease melioidosis. It is also capable of infecting plants. [4]

Aerobic organism

An aerobic organism or aerobe is an organism that can survive and grow in an oxygenated environment. In contrast, an anaerobic organism (anaerobe) is any organism that does not require oxygen for growth. Some anaerobes react negatively or even die if oxygen is present.

Melioidosis Human disease

Melioidosis is an infectious disease caused by a Gram-negative bacterium, Burkholderia pseudomallei, found in soil and water. It is of public health importance in endemic areas, particularly in northeast Thailand, Vietnam, and northern Australia. It exists in acute and chronic forms. Signs and symptoms may include pain in chest, bones, or joints; cough; skin infections, lung nodules, and pneumonia.

B. pseudomallei measures 2–5 μm in length and 0.4–0.8 μm in diameter and is capable of self-propulsion using flagella. The bacteria can grow in a number of artificial nutrient environments, especially betaine- and arginine-containing ones.

A betaine in chemistry is any neutral chemical compound with a positively charged cationic functional group such as a quaternary ammonium or phosphonium cation that bears no hydrogen atom and with a negatively charged functional group such as a carboxylate group that may not be adjacent to the cationic site. A betaine thus may be a specific type of zwitterion. Historically, the term was reserved for TMG (trimethylglycine) only. Biologically, betaine is involved in methylation reactions and detoxification of homocysteine.

Arginine chemical compound

Arginine, also known as L-arginine (symbol Arg or R), is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, an α-carboxylic acid group, and a side chain consisting of a 3-carbon aliphatic straight chain ending in a guanidino group. At physiological pH, the carboxylic acid is deprotonated (−COO), the amino group is protonated (−NH3+), and the guanidino group is also protonated to give the guanidinium form (-C-(NH2)2+), making arginine a charged, aliphatic amino acid. It is the precursor for the biosynthesis of nitric oxide. It is encoded by the codons CGU, CGC, CGA, CGG, AGA, and AGG.

In vitro , optimal proliferation temperature is reported around 40 °C in neutral or slightly acidic environments (pH 6.8–7.0). The majority of strains are capable of fermentation of sugars without gas formation (most importantly, glucose and galactose; older cultures are reported to also metabolize maltose and starch). Bacteria produce both exo- and endotoxins. The role of the toxins identified in the process of melioidosis symptom development has not been fully elucidated. [5]

<i>In vitro</i> test-tube experiments

In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from in vitro experiments may not fully or accurately predict the effects on a whole organism. In contrast to in vitro experiments, in vivo studies are those conducted in animals, including humans, and whole plants.

pH measure of the acidity or basicity of an aqueous solution

In chemistry, pH is a logarithmic scale used to specify the acidity or basicity of an aqueous solution. It is approximately the negative of the base 10 logarithm of the molar concentration, measured in units of moles per liter, of hydrogen ions. More precisely it is the negative of the base 10 logarithm of the activity of the hydrogen ion. At 25 °C, solutions with a pH less than 7 are acidic and solutions with a pH greater than 7 are basic. The neutral value of the pH depends on the temperature, being lower than 7 if the temperature increases. Pure water is neutral, pH 7 at (25 °C), being neither an acid nor a base. Contrary to popular belief, the pH value can be less than 0 or greater than 14 for very strong acids and bases respectively.

Sugar generic name for sweet-tasting, soluble carbohydrates

Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. The various types of sugar are derived from different sources. Simple sugars are called monosaccharides and include glucose, fructose, and galactose. "Table sugar" or "granulated sugar" refers to sucrose, a disaccharide of glucose and fructose. In the body, sucrose is hydrolysed into fructose and glucose.


B. pseudomallei is not fastidious and grows on a large variety of culture media (blood agar, MacConkey agar, EMB, etc.). Ashdown's medium (or Burkholderia cepacia medium) may be used for selective isolation. [6] Cultures typically become positive in 24 to 48 hours (this rapid growth rate differentiates the organism from B. mallei , which typically takes a minimum of 72 hours to grow). Colonies are wrinkled, have a metallic appearance, and possess an earthy odour. On Gram staining, the organism is a Gram-negative rod with a characteristic "safety pin" appearance (bipolar staining). On sensitivity testing, the organism appears highly resistant (it is innately resistant to a large number of antibiotics including colistin and gentamicin) and that again differentiates it from B. mallei, which is in contrast, exquisitely sensitive to a large number of antibiotics. For environmental specimens only, differentiation from the nonpathogenic B. thailandensis using an arabinose test is necessary (B. thailandensis is never isolated from clinical specimens). [7] The laboratory identification of B. pseudomallei has been described in the literature. [8]

MacConkey agar culture medium used in microbiology

MacConkey agar is an indicator, a selective and differential culture medium for bacteria designed to selectively isolate Gram-negative and enteric bacilli and differentiate them based on lactose fermentation. The crystal violet and bile salts inhibit the growth of Gram-positive organisms which allows for the selection and isolation of gram-negative bacteria. Enteric bacteria that have the ability to ferment lactose can be detected using the carbohydrate lactose, and the pH indicator neutral red.

Eosin methylene blue culture medium used in microbiology

Eosin methylene blue is a selective stain for gram-negative bacteria. EMB contains dyes that are toxic to gram-positive bacteria. EMB is the selective and differential medium for coliforms. It is a blend of two stains, eosin and methylene blue in the ratio of 6:1. A common application of this stain is in the preparation of EMB agar, a differential microbiological medium, which slightly inhibits the growth of Gram-positive bacteria and provides a color indicator distinguishing between organisms that ferment lactose and those that do not. Organisms that ferment lactose display "nucleated colonies"—colonies with dark centers.

Ashdowns medium

Ashdown's medium is a selective culture medium for the isolation and characterisation of Burkholderia pseudomallei.

The classic textbook description of B. pseudomallei in clinical samples is of an intracellular, bipolar-staining, Gram-negative rod, but this is of little value in identifying the organism from clinical samples. [8] Some [9] suggest the Wayson stain is useful for this purpose, but this has been shown not to be the case. [10]

Wayson stain

The Wayson stain is a basic fuchsin-methylene blue, ethyl alcohol-phenol microscopic staining procedure. It was originally a modified methylene blue stain used for diagnosing bubonic plague. With this stain, Yersinia pestis appears purple with a characteristic safety-pin appearance, which is due to the presence of a central vacuole.

Laboratory identification of B. pseudomallei can be difficult, especially in Western countries where it is rarely seen. The large, wrinkled colonies look like environmental contaminants, so are often discarded as being of no clinical significance. Colony morphology is very variable and a single strain may display multiple colony types, [11] [12] so inexperienced laboratory staff may mistakenly believe the growth is not pure. The organism grows more slowly than other bacteria that may be present in clinical specimens, and in specimens from nonsterile sites, is easily overgrown. Nonsterile specimens should, therefore, be cultured in selective media (e.g., Ashdown's [13] [14] or B. cepacia medium). [6] For heavily contaminated samples, such as faeces, a modified version of Ashdown's that includes norfloxacin, amoxicillin, and polymyxin B has been proposed. [15] In blood culture, the BacT/ALERT MB system (normally used for culturing mycobacteria) by bioMérieux has been shown to have superior yields compared to conventional blood culture media. [16]

Norfloxacin chemical compound

Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.

Amoxicillin antibiotic useful for the treatment of a number of bacterial infections

Amoxicillin is an antibiotic often used for the treatment of a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less commonly by injection.

Polymyxin B chemical compound

Polymyxin B is an antibiotic primarily used for resistant Gram-negative infections. It is derived from the bacterium Bacillus polymyxa. Polymyxin B is composed of a number of related compounds. It has a bactericidal action against almost all Gram-negative bacilli except the Proteus and Neisseria genera. Polymyxins bind to the cell membrane and alter its structure, making it more permeable. The resulting water uptake leads to cell death. Polymyxins are cationic, basic peptides that act like detergents (surfactants). Side effects include neurotoxicity and acute renal tubular necrosis. Polymyxins are used in the topical first-aid preparation Neosporin.

  1. Family of polypeptides with attached fatty acid; cationic detergent at physiological pH, both hydrophilic and hydrophobic properties
  2. Bactericidal for gram-negative; little to no effect on gram-positive, since cell wall is too thick to permit access to membrane

Even when the isolate is recognised to be significant, commonly used identification systems may misidentify the organism as Chromobacterium violaceum or other nonfermenting, Gram-negative bacilli such as Burkholderia cepacia or Pseudomonas aeruginosa . [17] [18] Again, because the disease is rarely seen in Western countries, identification of B. pseudomallei in cultures may not actually trigger alarms in physicians unfamiliar with the disease. [19] Routine biochemical methods for identification of bacteria vary widely in their identification of this organism: the API 20NE system accurately identifies B. pseudomallei in 99% of cases, [20] as does the automated Vitek 1 system, but the automated Vitek 2 system only identifies 19% of isolates. [18]

The pattern of resistance to antimicrobials is distinctive, and helps to differentiate the organism from P. aeruginosa. The majority of B. pseudomallei isolates are intrinsically resistant to all aminoglycosides (via an efflux pump mechanism), [21] but sensitive to co-amoxiclav: [22] this pattern of resistance almost never occurs in P. aeruginosa and is helpful in identification. [23] Unfortunately, the majority of strains in Sarawak, Borneo, are susceptible to aminoglycosides and macrolides, which means the conventional recommendations for isolation and identification do not apply there. [24]

Molecular methods (PCR) of diagnosis are possible, but not routinely available for clinical diagnosis. [25] [26] Fluorescence in situ hybridisation has also been described, but has not been clinically validated, and it is not commercially available. [27] In Thailand, a latex agglutination assay is widely used, [20] while a rapid immunofluorescence technique is also available in a small number of centres. [28]


B. pseudomallei is susceptible to numerous disinfectants, including benzalkonium chloride, iodine, mercuric chloride, potassium permanganate, 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, and to a lesser extent, phenolic preparations. [29] B. pseudomallei is effectively killed by the commercial disinfectants, Perasafe and Virkon. [30] The microorganism can also be destroyed by heating to above 74 °C for 10 min or by ultraviolet irradiation. [31] B. pseudomallei is not reliably disinfected by chlorine. [32] [33]

Medical importance

B. pseudomallei infection in humans is called melioidosis; its mortality is 20 to 50% even with treatment. [22]

Antibiotic treatment and sensitivity testing

The antibiotic of choice is ceftazidime. [22] While various antibiotics are active in vitro (e.g., chloramphenicol, doxycycline, co-trimoxazole), they have been proven to be inferior in vivo for the treatment of acute melioidosis. [34] Disc diffusion tests are unreliable when looking for co-trimoxazole resistance in B. pseudomallei (they greatly overestimate resistance) and Etests or agar dilution tests should be used in preference. [35] [36] The actions of co-trimoxazole and doxycycline are antagonistic, which suggests these two drugs ought not to be used together. [37]

The organism is intrinsically resistant to gentamicin [38] and colistin, and this fact is helpful in the identification of the organism. [39] Kanamycin is used to kill B. pseudomallei in the laboratory, but the concentrations used are much higher than those achievable in humans. [40]

Pathogenicity mechanisms and virulence factors

B. pseudomallei is an opportunistic pathogen. An environmental organism, it has no requirement to pass through an animal host to replicate. From the point of view of the bacterium, human infection is a developmental "dead end". [41]

Strains which cause disease in humans differ from those causing disease in other animals, by possessing certain genomic islands. [42] It may have the ability to cause disease in humans because of DNA it has acquired from other microorganisms. [42] Its mutation rate is also high, and the organism continues to evolve even after infecting a host. [43]

B. pseudomallei is able to invade cells (it is an intracellular pathogen). [44] It is able to polymerise actin, and to spread from cell to cell, causing cell fusion and the formation of multinucleated giant cells. [45] It possesses a uniquely fusogenic type VI secretion system that is required for cell-cell spread and virulence in mammalian hosts. [46] The bacterium also expresses a toxin called lethal factor 1. [47] B. pseudomallei is one of the first Proteobacteria to be identified as containing an active type VI secretion system. It is also the only organism identified that contains up to six different type VI secretion systems. [48]

B. pseudomallei is intrinsically resistant to a large number of antimicrobial agents by virtue of its efflux pump mechanism. This mediates resistance to aminoglycosides (AmrAB-OprA), tetracyclines, fluoroquinolones, and macrolides (BpeAB-OprB). [49]

Vaccine candidates

No vaccine is currently available, but a number of vaccine candidates have been suggested. Aspartate-β-semialdehyde dehydrogenase (asd) gene deletion mutants are auxotrophic for diaminopimelate (DAP) in rich media and auxotrophic for DAP, lysine, methionine, and threonine in minimal media. [50] The Δasd bacterium (bacterium with the asd gene removed) protects against inhalational melioidosis in mice. [51]

Related Research Articles

<i>Pseudomonas</i> genus of bacteria

Pseudomonas is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 validly described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a wide range of niches. Their ease of culture in vitro and availability of an increasing number of Pseudomonas strain genome sequences has made the genus an excellent focus for scientific research; the best studied species include P. aeruginosa in its role as an opportunistic human pathogen, the plant pathogen P. syringae, the soil bacterium P. putida, and the plant growth-promoting P. fluorescens.

Glanders is an infectious disease that occurs primarily in horses, mules, and donkeys. It can be contracted by other animals, such as dogs, cats, goats and humans. It is caused by infection with the bacterium Burkholderia mallei, usually by ingestion of contaminated feed or water. Signs of glanders include the formation of nodular lesions in the lungs and ulceration of the mucous membranes in the upper respiratory tract. The acute form results in coughing, fever, and the release of an infectious nasal discharge, followed by septicaemia and death within days. In the chronic form, nasal and subcutaneous nodules develop, eventually ulcerating. Death can occur within months, while survivors act as carriers.

<i>Burkholderia</i> genus of bacteria

Burkholderia is a genus of Proteobacteria whose pathogenic members include the Burkholderia cepacia complex which attacks humans and Burkholderia mallei, responsible for glanders, a disease that occurs mostly in horses and related animals; Burkholderia pseudomallei, causative agent of melioidosis; and Burkholderia cepacia, an important pathogen of pulmonary infections in people with cystic fibrosis (CF).

Burkholderiaceae family of bacteria

The Burkholderiaceae are a family of bacteria included in the order Burkholderiales. It includes some pathogenic species, such as Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis).

Bartonellosis is an infectious disease produced by bacteria of the genus Bartonella. Bartonella species cause diseases such as Carrión´s disease, trench fever, cat-scratch disease, bacillary angiomatosis, peliosis hepatis, chronic bacteremia, endocarditis, chronic lymphadenopathy, and neurological disorders.

<i>Burkholderia cepacia</i> complex species of bacterium

Burkholderia cepacia complex (BCC), or simply Burkholderia cepacia, is a group of catalase-producing, lactose-nonfermenting, Gram-negative bacteria composed of at least 20 different species, including B. cepacia, B. multivorans, B. cenocepacia, B. vietnamiensis, B. stabilis, B. ambifaria, B. dolosa, B. anthina, B. pyrrocinia and B. ubonensis. B. cepacia is an opportunistic human pathogen that most often causes pneumonia in immunocompromised individuals with underlying lung disease. Patients with sickle-cell haemoglobinopathies are also at risk. The species also attacks young onion and tobacco plants, as well as displaying a remarkable ability to digest oil.

Stenotrophomonas maltophilia is an aerobic, nonfermentative, Gram-negative bacterium. It is an uncommon bacterium and human infection is difficult to treat. Initially classified as Bacterium bookeri, then renamed Pseudomonas maltophilia, S. maltophilia was also grouped in the genus Xanthomonas before eventually becoming the type species of the genus Stenotrophomonas in 1993.

<i>Burkholderia mallei</i> species of bacterium

Burkholderia mallei is a Gram-negative, bipolar, aerobic bacterium, a human and animal pathogen of genus Burkholderia causing glanders; the Latin name of this disease (malleus) gave its name to the species causing it. It is closely related to B. pseudomallei, and by multilocus sequence typing it is a subspecies of B. pseudomallei.B. mallei evolved from B. pseudomallei by selective reduction and deletions from the B. pseudomallei genome. Unlike B. pseudomallei and other genus members, B. mallei is nonmotile; its shape is coccobacillary measuring some 1.5–3.0 μm in length and 0.5–1.0 μm in diameter with rounded ends.

Dientamoebiasis is a medical condition caused by infection with Dientamoeba fragilis, a single-cell parasite that infects the lower gastrointestinal tract of humans. It is an important cause of traveler's diarrhea, chronic abdominal pain, chronic fatigue, and failure to thrive in children.

<i>Chromobacterium violaceum</i> species of bacterium

Chromobacterium violaceum is a Gram-negative, facultative anaerobic, non-sporing coccobacillus. It is motile with the help of a single flagellum which is located at the pole of the coccobacillus. Usually, there are one or two more lateral flagella as well. It is part of the normal flora of water and soil of tropical and sub-tropical regions of the world. It produces a natural antibiotic called violacein, which may be useful for the treatment of colon and other cancers. It grows readily on nutrient agar, producing distinctive smooth low convex colonies with a dark violet metallic sheen. Some strains of the bacteria which do not produce this pigment have also been reported. It has the ability to break down tarballs.

<i>Burkholderia thailandensis</i> species of bacterium

Burkholderia thailandensis is a nonfermenting motile, Gram-negative bacillus that occurs naturally in soil. It is closely related to Burkholderia pseudomallei, but unlike B. pseudomallei, it only rarely causes disease in humans or animals. The lethal inoculum is approximately 1000 times higher than for B. pseudomallei. It is usually distinguished from B. pseudomallei by its ability to assimilate arabinose. Other differences between these species include lipopolysaccharide composition, colony morphology, and differences in metabolism.

<i>Actinobacillus</i> genus of bacteria

Actinobacillus is a genus of Gram-negative, nonmotile and non-spore-forming, oval to rod-shaped bacteria occurring as parasites or pathogens in mammals, birds, and reptiles. It is a member of the Pasteurellaceae family. The bacteria are facultatively aerobic or anaerobic, capable of fermenting carbohydrates, and of reducing nitrates. The genomic DNA contains between 40 and 47 mol % guanine plus cytosine.

<i>Rickettsia conorii</i> species of bacterium

Rickettsia conorii is a Gram-negative, obligate intracellular bacterium of the genus Rickettsia that causes human disease called Boutonneuse fever, Mediterranean spotted fever, Israeli tick typhus, Astrakhan spotted fever, Kenya tick typhus, Indian tick typhus, or other names that designate the locality of occurrence while having distinct clinical features. It is a member of the spotted fever group and the most geographically dispersed species in the group, recognized in most of the regions bordering on the Mediterranean Sea and Black Sea, Israel, Kenya, and other parts of North, Central, and South Africa, and India. The prevailing vector is the brown dog tick, Rhipicephalus sanguineus. The bacterium was isolated by Emile Brumpt in 1932 and named after A. Conor who, in collaboration with A. Bruch, provided the first description of boutonneuse fever in Tunisia in 1910.

<i>Staphylococcus capitis</i> species of bacterium

Staphylococcus capitis is a coagulase-negative species (CoNS) of Staphylococcus. It is part of the normal flora of the skin of the human scalp, face, neck, and ears and has been associated with prosthetic valve endocarditis, but is rarely associated with native valve infection.

Phaeoacremonium is a fungus genus associated with wilt and decline diseases of woody hosts and human infections.

Burkholderia contaminans is a gram-negative, bacterium from the genus of Burkholderia and the family of Burkholderiaceae and belongs to the Burkholderia cepacia complex, which was isolated from cystic fibrosis patients in Argentina. Burkholderia acidipaludis can cause biliary sepsis.

Ornibactin chemical compound

Ornibactin is a siderophore, or small iron-binding compound secreted by bacteria to transport iron into the cell. Ornibactin is produced by Burkholderia cenocepacia under iron-deficient conditions. B. cenocepacia is known to opportunistically infect humans, specifically ones suffering from cystic fibrosis.


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