Burkholderia Cepacia
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''Burkholderia cepacia'' complex (BCC), or simply ''Burkholderia cepacia'', is a group of
catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...
-producing,
lactose Lactose is a disaccharide sugar synthesized by galactose and glucose subunits and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from ' (gen. '), the Latin word for milk, plus the suffix '' - ...
-non
fermenting Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food ...
,
Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
bacteria Bacteria (; singular: 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 ...
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 Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
in
immunocompromise Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
d individuals with underlying lung disease (such as
cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...
or
chronic granulomatous disease Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reacti ...
). Patients with sickle-cell haemoglobinopathies are also at risk. The species complex also attacks young
onion An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus ''Allium''. The shallot is a botanical variety of the onion ...
and
tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...
plants, and displays a remarkable ability to digest
oil An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...
. ''Burkholderia cepacia'' is also found in marine environments ( marine sponges) and some strains of ''Burkholderia cepacia'' can tolerate high salinity. S.I. Paul et al. (2021) isolated and biochemically characterized salt tolerant strains of ''Burkholderia cepacia'' from marine sponges of Saint Martin's Island of the
Bay of Bengal The Bay of Bengal is the northeastern part of the Indian Ocean, bounded on the west and northwest by India, on the north by Bangladesh, and on the east by Myanmar and the Andaman and Nicobar Islands of India. Its southern limit is a line between ...
,
Bangladesh Bangladesh (}, ), officially the People's Republic of Bangladesh, is a country in South Asia. It is the eighth-most populous country in the world, with a population exceeding 165 million people in an area of . Bangladesh is among the mos ...
.


Pathogenesis

BCC organisms are typically found in water and soil and can survive for prolonged periods in moist environments. They show a relatively poor
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...
. Virulence factors include adherence to plastic surfaces (including those of medical devices) and production of several enzymes such as
elastase In molecular biology, elastase is an enzyme from the class of ''proteases (peptidases)'' that break down proteins. In particular, it is a serine protease. Forms and classification Eight human genes exist for elastase: Some bacteria (includin ...
and
gelatinase Gelatinases are enzymes capable of degrading gelatin. Gelatinases are expressed in several bacteria including ''Pseudomonas aeruginosa'' and ''Serratia marcescens''. In humans, the gelatinases are matrix metalloproteinases MMP2 and MMP9 Matrix ...
. Also relevant might be their ability to survive attacks from
neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
. Person-to-person spread has been documented; as a result, many hospitals, clinics, and camps have enacted strict isolation precautions for those infected with BCC. Infected individuals are often treated in a separate area from uninfected patients to limit spread, since BCC infection can lead to a rapid decline in
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
function and result in death.


Diagnosis

Diagnosis of BCC involves culturing the bacteria from clinical specimens, such as
sputum Sputum is mucus that is coughed up from the lower airways (the trachea and bronchi). In medicine, sputum samples are usually used for a naked eye examination, microbiological investigation of respiratory infections and cytological investigations ...
or blood. BCC organisms are naturally resistant to many common
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
, including
aminoglycosides Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...
and
polymyxin B Polymyxin B, sold under the brand name Poly-Rx among others, is an antibiotic used to treat meningitis, pneumonia, sepsis, and urinary tract infections. While it is useful for many Gram negative infections, it is not useful for Gram positive infe ...
. and this fact is exploited in the identification of the organism. The organism is usually cultured in ''Burkholderia cepacia'' agar (BC agar), which contains
crystal violet Crystal violet or gentian violet, also known as methyl violet 10B or hexamethyl pararosaniline chloride, is a triarylmethane dye used as a histological stain and in Gram's method of classifying bacteria. Crystal violet has antibacterial, antif ...
and bile salts to inhibit the growth of Gram-positive cocci, and
ticarcillin Ticarcillin is a carboxypenicillin. It can be sold and used in combination with clavulanate as ticarcillin/clavulanic acid. Because it is a penicillin, it also falls within the larger class of beta-lactam antibiotics. Its main clinical use is as an ...
and
polymyxin B Polymyxin B, sold under the brand name Poly-Rx among others, is an antibiotic used to treat meningitis, pneumonia, sepsis, and urinary tract infections. While it is useful for many Gram negative infections, it is not useful for Gram positive infe ...
to inhibit the growth of other Gram-negative bacilli. It also contains
phenol red Phenol red (also known as phenolsulfonphthalein or PSP) is a pH indicator frequently used in cell biology laboratories. Chemical structure and properties Phenol red exists as a red crystal that is stable in air. Its solubility is 0.77 grams per ...
pH indicator which turns pink when it reacts with alkaline byproducts generated by the bacteria when it grows. Alternatively, oxidation-fermentation polymyxin-bacitracin-lactose (OFPBL) agar can be used. OFPBL contains
polymyxin Polymyxins are antibiotics. Polymyxins B and E (also known as colistin) are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane. They are part of a broader class of molecules ...
(which kills most Gram-negative bacteria, including ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...
'') and
bacitracin Bacitracin is a polypeptide antibiotic. It is a mixture of related cyclic peptides produced by ''Bacillus licheniformis'' bacteria, that was first isolated from the variety "Tracy I" ( ATCC 10716) in 1945. These peptides disrupt Gram-positive bac ...
(which kills most Gram-positive bacteria and ''
Neisseria ''Neisseria'' is a large genus of bacteria that colonize the mucosal surfaces of many animals. Of the 11 species that colonize humans, only two are pathogens, '' N. meningitidis'' and ''N. gonorrhoeae''. ''Neisseria'' species are Gram-negativ ...
'' species). It also contains
lactose Lactose is a disaccharide sugar synthesized by galactose and glucose subunits and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from ' (gen. '), the Latin word for milk, plus the suffix '' - ...
, and organisms such as BCC that do not ferment lactose turn the pH indicator yellow, which helps to distinguish it from other organisms that may grow on OFPBL agar, such as '' Candida'' species, ''
Pseudomonas fluorescens ''Pseudomonas fluorescens'' is a common Gram-negative, rod-shaped bacterium. It belongs to the ''Pseudomonas'' genus; 16S rRNA analysis as well as phylogenomic analysis has placed ''P. fluorescens'' in the ''P. fluorescens'' group within the genu ...
'', and ''
Stenotrophomonas ''Stenotrophomonas'' is a genus of Gram-negative bacteria, comprising at least ten species. The main reservoirs of Stenotrophomonas are soil and plants. ''Stenotrophomonas'' species range from common soil organisms (''S. nitritireducens'') to o ...
'' species.


Treatment

Treatment typically includes multiple antibiotics and may include
ceftazidime Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, ...
,
minocycline Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also ...
,
piperacillin Piperacillin is a broad-spectrum β-lactam antibiotic of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into Gram-negative bacteria and redu ...
,
meropenem Meropenem, sold under the brand name Merrem among others, is an intravenous β-lactam antibiotic used to treat a variety of bacterial infections. Some of these include meningitis, intra-abdominal infection, pneumonia, sepsis, and anthrax. Comm ...
,
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 injection into a vein, it is used to treat meningitis, plague, cholera, a ...
, and
trimethoprim/sulfamethoxazole Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazo ...
(co-trimoxazole). Although co-trimoxazole has been generally considered the drug of choice for ''B. cepacia'' infections, ceftazidime, minocycline, piperacillin, and meropenem are considered to be viable alternative options in cases where co-trimoxazole cannot be administered because of hypersensitivity reactions, intolerance, or resistance. Newer beta-lactam / beta-lactamase combinations like ceftazidime-avibactam or ceftolozane-tazobactam can also be effective. ''Burkholderia cepacia'' is intrinsically resistant to
colistin Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as ''Pseudomonas aeruginosa'', ''Klebsiella ...
and usually resistant to
aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...
s. In people with cystic fibrosis, evidence is insufficient about the effectiveness of long-term antibiotic treatment with continuous inhaled aztreonam lysine (AZLI) in terms of lung function or chest infections.


History

''B. cepacia'' was discovered by
Walter Burkholder Walter Hagemeyer Burkholder (February 1, 1891– January 31, 1983) was an American plant pathologist who helped establish the role of bacteria as plant pathogens. He was awarded a Ph.D. by Cornell University in 1917 and subsequently appointed as pro ...
in 1949 as the cause of onion skin rot, and first described as a human
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
in the 1950s. It was first isolated in patients with cystic fibrosis (CF) in 1977, when it was known as ''Pseudomonas cepacia''. In the 1980s, outbreaks of ''B. cepacia'' in individuals with CF were associated with a 35% death rate. ''B. cepacia'' has a large
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
, containing twice the amount of genetic material as ''
E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
''.


See also

*
Contamination control Contamination control is the generic term for all activities aiming to control the existence, growth and proliferation of contamination in certain areas. Contamination control may refer to the atmosphere as well as to surfaces, to particulate matte ...
*
Povidone-iodine Povidone-iodine (PVP-I), also known as iodopovidone, is an antiseptic used for skin disinfection before and after surgery. It may be used both to disinfect the hands of healthcare providers and the skin of the person they are caring for. It may a ...
(contamination by BCC)


References


Further reading

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External links

*
''Burkholderia cepacia complex''
in the NCBI Taxonomy Browser
Type strain of ''Burkholderia cepacia complex''
at BacDive, the Bacterial Diversity Metadatabase
Type strain of ''Burkholderia cepacia''
at BacDive, the Bacterial Diversity Metadatabase {{DEFAULTSORT:Burkholderia Cepacia Complex Bacterial diseases Burkholderiaceae Healthcare-associated infections