B. Pseudomallei
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''Burkholderia pseudomallei'' (also known as ''Pseudomonas pseudomallei'') is a
Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
, bipolar, aerobic,
motile Motility is the ability of an organism to move independently using metabolic energy. This biological concept encompasses movement at various levels, from whole organisms to cells and subcellular components. Motility is observed in animals, mi ...
rod-shaped
bacterium Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...
. It is a soil-dwelling bacterium endemic in
tropical The tropics are the regions of Earth surrounding the equator, where the sun may shine directly overhead. This contrasts with the temperate or polar regions of Earth, where the Sun can never be directly overhead. This is because of Earth's ax ...
and
subtropical The subtropical zones or subtropics are geographical zone, geographical and Köppen climate classification, climate zones immediately to the Northern Hemisphere, north and Southern Hemisphere, south of the tropics. Geographically part of the Ge ...
regions worldwide, particularly in Thailand and northern Australia. It was reported in 2008 that there had been an expansion of the affected regions due to significant natural disasters, and it could be found in Southern China, Hong Kong, and countries in the Americas. ''B. pseudomallei'', amongst other pathogens, has been found in monkeys imported into the United States from Asia for laboratory use, posing a risk that the pathogen could be introduced into the country. Although it is mainly a soil-dwelling bacterium, one study showed that ''Burkholderia pseudomallei'' survived in distilled water for 16 years, demonstrating that it is capable of living in water if a specific environment is provided. It is resistant to a variety of harsh conditions including nutrient deficiency, extreme temperature or pH. It infects humans, causing the disease
melioidosis Melioidosis is an infectious disease caused by a gram-negative bacterium called ''Burkholderia pseudomallei''. Most people exposed to ''B. pseudomallei'' experience no symptoms, but complications can range from fever and skin changes to pneumon ...
; mortality is 20–50% even with treatment. The
CDC The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...
classifies it as a "Tier 1 select agent" with potential as a
bioterrorism Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents include bacteria, viruses, insects, fungi, and/or their toxins, and may be in a naturally occurring or a human-modified form, in mu ...
agent. It infects other animals, most commonly livestock such as goats, pigs, and sheep, less frequently. It is also capable of infecting plants in a laboratory setting. ''Burkholderia pseudomallei'' measures 2–5 μm in length and 0.4–0.8 μm in diameter and is capable of self-propulsion using
flagella A flagellum (; : flagella) (Latin for 'whip' or 'scourge') is a hair-like appendage that protrudes from certain plant and animal sperm cells, from fungal spores ( zoospores), and from a wide range of microorganisms to provide motility. Many pr ...
. The bacteria can grow in a number of artificial nutrient environments, especially
betaine A betaine () in chemistry is any neutral chemical compound with a positively charged cationic functional group that bears no hydrogen atom, such as a Quaternary ammonium cation, quaternary ammonium or phosphonium cation (generally: Onium compou ...
- and
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
-containing ones. ''
In vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
'', 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 oxidation, not fermentation, of
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecul ...
s without gas formation (most importantly,
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
and
galactose Galactose (, ''wikt:galacto-, galacto-'' + ''wikt:-ose#Suffix 2, -ose'', ), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweetness, sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epime ...
; older cultures are reported to also metabolize
maltose } Maltose ( or ), also known as maltobiose or malt sugar, is a disaccharide formed from two units of glucose joined with an α(1→4) bond. In the isomer isomaltose, the two glucose molecules are joined with an α(1→6) bond. Maltose is the tw ...
and
starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diet ...
). Bacteria produce both exo- and
endotoxin Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...
s. The role of the toxins identified in the process of melioidosis symptom development has not been fully elucidated.


Identification

''Burkholderia pseudomallei'' is not fastidious and grows on a large variety of culture media (
blood agar An agar plate is a Petri dish that contains a growth medium solidified with agar, used to Microbiological culture, culture microorganisms. Sometimes selective compounds are added to influence growth, such as antibiotics. Individual microorganism ...
, MacConkey agar, EMB, etc.). Ashdown's medium (or ''Burkholderia cepacia'' medium) may be used for selective isolation. 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 odor. On
Gram staining Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. It may also be used to diagnose a fungal infection. The name comes ...
, the organism is a
Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
rod with a characteristic "safety pin" appearance (bipolar staining). On sensitivity testing, the organism appears highly resistant (it is innately resistant to many antibiotics including colistin and
gentamicin Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis amo ...
) and that again differentiates it from ''B. mallei'', which is in contrast, exquisitely sensitive to many antibiotics. For environmental specimens only, differentiation from the nonpathogenic '' B. thailandensis'' using an
arabinose Arabinose is an aldopentose – a monosaccharide containing five carbon atoms, and including an aldehyde (CHO) functional group. Properties For biosynthetic reasons, most saccharides are almost always more abundant in nature as the "D"-form, o ...
test is necessary (''B. thailandensis'' is never isolated from clinical specimens). The laboratory identification of ''B. pseudomallei'' has been described in the literature. 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. Some suggest the Wayson stain is useful for this purpose, but this has been shown not to be the case. 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, 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 or ''B. cepacia'' medium). For heavily contaminated samples, such as feces, a modified version of Ashdown's that includes
norfloxacin Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteri ...
,
amoxicillin Amoxicillin is an antibiotic medication belonging to the aminopenicillin class of the penicillin family. The drug is used to treat bacterial infections such as middle ear infection, strep throat, pneumonia, skin infections, odontogenic inf ...
, and polymyxin B has been proposed. In blood culture, the BacT/ALERT MB system (normally used for culturing
mycobacteria ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') a ...
) by bioMérieux has been shown to have superior yields compared to conventional blood culture media. Even when the isolate is recognized to be significant, commonly used identification systems may misidentify the organism as ''
Chromobacterium violaceum ''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 ...
'' or other nonfermenting, Gram-negative bacilli such as '' Burkholderia cepacia'' or ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...
''. 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. Routine biochemical methods for identification of bacteria vary widely in their identification of this organism: the
API An application programming interface (API) is a connection between computers or between computer programs. It is a type of software interface, offering a service to other pieces of software. A document or standard that describes how to build ...
20NE system accurately identifies ''B. pseudomallei'' in 99% of cases, as does the automated Vitek 1 system, but the automated Vitek 2 system only identifies 19% of isolates. 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), but sensitive to co-amoxiclav: this pattern of resistance almost never occurs in ''P. aeruginosa'' and is helpful in identification. 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. Molecular methods ( PCR) of diagnosis are possible, but not routinely available for clinical diagnosis. Fluorescence ''in situ'' hybridisation has also been described, but has not been clinically validated, and it is not commercially available. In Thailand, a latex agglutination assay is widely used, while a rapid immunofluorescence technique is also available in a small number of centres.


Characteristics

Morphological, physiological, and biochemical characteristics of ''Burkholderia pseudomallei'' are shown in the Table below. Note: + = Positive, – =Negative


Disinfection

''Burkholderia pseudomallei'' is susceptible to numerous disinfectants, including
benzalkonium chloride Benzalkonium chloride (BZK, BKC, BAK, BAC), also known as alkyldimethylbenzylammonium chloride (ADBAC) is a type of cationic surfactant. It is an organic salt classified as a quaternary ammonium compound. ADBACs have three main categories of use: ...
,
iodine Iodine is a chemical element; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid that melts to form a deep violet liquid at , and boils to a vi ...
,
mercuric chloride Mercury(II) chloride (mercury bichloride, mercury dichloride, mercuric chloride), historically also sulema or corrosive sublimate, is the inorganic chemical compound of mercury and chlorine with the formula HgCl2, used as a laboratory reagent. ...
,
potassium permanganate Potassium permanganate is an inorganic compound with the chemical formula KMnO4. It is a purplish-black crystalline salt, which dissolves in water as K+ and ions to give an intensely pink to purple solution. Potassium permanganate is widely us ...
, 1%
sodium hypochlorite Sodium hypochlorite is an alkaline inorganic chemical compound with the formula (also written as NaClO). It is commonly known in a dilute aqueous solution as bleach or chlorine bleach. It is the sodium salt of hypochlorous acid, consisting of ...
, 70%
ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...
, 2%
glutaraldehyde Glutaraldehyde is an organic compound with the formula . The molecule consists of a five carbon chain doubly terminated with formyl (CHO) groups. It is usually used as a solution in water, and such solutions exists as a collection of hydrates, ...
, and to a lesser extent, phenolic preparations. ''B. pseudomallei'' is effectively killed by the commercial disinfectants, Perasafe and Virkon. The microorganism can also be destroyed by heating to above 74 °C for 10 min or by
ultraviolet Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of ...
irradiation.


Medical importance

''Burkholderia pseudomallei'' infection in humans is called
melioidosis Melioidosis is an infectious disease caused by a gram-negative bacterium called ''Burkholderia pseudomallei''. Most people exposed to ''B. pseudomallei'' experience no symptoms, but complications can range from fever and skin changes to pneumon ...
or Whitmore's disease. It is spread though direct contact with water or soil that holds the bacteria. There have been few cases of transmission of the bacteria perinatally. Its mortality is 20 to 50% even with treatment.


Antibiotic treatment and sensitivity testing

The antibiotic of choice is ceftazidime. While various
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s are active ''in vitro'' (e.g.,
chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by intravenous, injection into a vein, it is used to treat meningitis, pl ...
,
doxycycline Doxycycline is a Broad-spectrum antibiotic, broad-spectrum antibiotic of the Tetracycline antibiotics, tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat pneumonia, bacterial p ...
,
co-trimoxazole Trimethoprim/sulfamethoxazole, sold under the trade names Bactrim, Cotrim (a short form of the British Approved Name, Co-trimoxazole) and Septra, among others, is a fixed-dose combination antibiotic medication used to treat a variety of bac ...
), they have been proven to be inferior ''in vivo'' for the treatment of acute melioidosis. Disc diffusion tests are unreliable when looking for co-trimoxazole resistance in ''B. pseudomallei'' (they greatly overestimate resistance) and
Etest Etest (previously known as the Epsilometer test) is a way of determining antimicrobial sensitivity by placing a strip impregnated with antimicrobials onto an agar plate. A strain of bacterium or fungus will not grow near a concentration of anti ...
s or agar dilution tests should be used in preference. The actions of co-trimoxazole and doxycycline are antagonistic, which suggests these two drugs ought not to be used together. The organism is intrinsically resistant to
gentamicin Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis amo ...
and colistin, and this fact is helpful in the identification of the organism.
Kanamycin Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamy ...
is used to kill ''B. pseudomallei'' in the laboratory, but the concentrations used are much higher than those achievable in humans.


Pathogenicity mechanisms and virulence factors

''Burkholderia pseudomallei'' is an opportunistic pathogen and, since its an environmental organism, 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". Strains which cause disease in humans differ from those causing disease in other animals, by possessing certain genomic islands. It may have the ability to cause disease in humans via DNA acquired from other microorganisms. Its mutation rate is also high, and the organism continues to evolve even after infecting a host. ''Burkholderia pseudomallei'' is able to invade cells - being an intracellular pathogen. It is able to polymerise
actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
, and to spread from cell to cell, causing cell fusion and the formation of multinucleated giant cells. It possesses a uniquely fusogenic type VI secretion system that is required for cell-cell spread and virulence in mammalian hosts. The bacterium also expresses a toxin called lethal factor 1. ''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. ''B. pseudomallei'' is intrinsically resistant to many antimicrobial agents by virtue of its
efflux pump An efflux pump is an active transporter in cells that moves out unwanted material. Efflux pumps are an important component in bacteria, particularly in their ability to remove antibiotics. The efflux process can also involve the movement of hea ...
mechanism. This mediates resistance to
aminoglycosides Aminoglycoside is a medicinal chemistry, medicinal and bacteriology, bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside ...
(''AmrAB-OprA''),
tetracyclines Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. ...
,
fluoroquinolones Quinolone antibiotics constitute a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ve ...
, and
macrolides Macrolides are a class of mostly natural products with a large macrocycle, macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural prod ...
(''BpeAB-OprB'').


Vaccine candidates

no vaccine had been licensed, although many had been evaluated in pre-clinical studies. Vaccine candidates have been suggested. Aspartate-β-semialdehyde dehydrogenase (''asd'') gene deletion mutants are
auxotrophic Auxotrophy ( "to increase"; ''τροφή'' "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). An auxotroph is an organism that displays this characteristic; ''a ...
for diaminopimelate (DAP) in rich media and auxotrophic for DAP,
lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
,
methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...
and
threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form when dissolved in water), a carboxyl group (which is in the deprotonated −COO− ...
in minimal media. The Δ''asd'' bacterium (bacterium with the ''asd'' gene removed) protects against inhalational melioidosis in mice.


Transformation

''Burkholderia pseudomoallei'' can go through transformation. The bacteria is able to uptake a free plasmid using electroporation and the plasmid material will integrate into the host DNA when they are electrocompetent.


Footnotes


References


External links

* *
Pathema
''Burkholderia'' resource * {{Taxonbar, from=Q140475 Burkholderiaceae Bacteria described in 1993