''Burkholderia cenocepacia'' is a Gram-negative, rod-shaped bacterium that is commonly found in soil and water environments and may also be associated with plants and animals, particularly as a human pathogen. It is one of over 20 species in the
''Burkholderia cepacia'' complex (Bcc) and is notable due to its virulence factors and inherent antibiotic resistance that render it a prominent opportunistic pathogen responsible for life-threatening,
nosocomial
A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other health care facility. To emphasize both hospital and nonhospital settings, it is ...
infections in immunocompromised patients, such as those with
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 ...
. The
quorum sensing
In biology, quorum sensing or quorum signalling (QS) is the ability to detect and respond to cell population density by gene regulation. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at ...
systems CepIR and CciIR regulate the formation of biofilms and the expression of virulence factors such as
siderophore
Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is no ...
s and proteases. ''Burkholderia cenocepacia'' may also cause disease in plants, such as in onions and bananas.
Additionally, some strains serve as plant growth-promoting
rhizobacteria
Rhizobacteria are root-associated bacteria that can have a detrimental (parasitic varieties), neutral or beneficial effect on plant growth. The name comes from the Greek ''rhiza'', meaning root. The term usually refers to bacteria that form symbio ...
.
Taxonomy
Within the ''Burkholderia'' genus, the ''Burkholderia cepacia'' complex contains over 20 related species that cause opportunistic infections and possess antibiotic resistance.
''Burkholderia cepacia'' was originally defined as a single species, but it is now one of several species in the Bcc. Although closely related, the species within the Bcc have differing severity of pathogenicity, and ''B. cenocepacia'' is one of the most intensively studied due to its higher pathogenicity and antibiotic resistance compared to other species in the complex.
Exchange of genetic material between species of the Bcc has resulted in a
reticulated phylogeny that presents an obstacle to diagnostic classification at the species-level.
Because of this phenotypic overlap between species, previous nomenclature of Bcc species involved
genomovar terms, with ''Burkholderia cenocepacia'' categorized as genomovar III of the Bcc.
Within the categorization as genomovar III, there are 4 phylogenetic lineage groups: IIIA, IIIB, IIIC, and IIID.
No IIIC isolates have been found in studies on the natural environment, whereas all IIID isolates studied have been in clinical isolates of ''B. cenocepacia''.
Microbiology
The strong environmental protection response of ''B. cenocepacia'' is attributed to the biofilm formed by groups of the organism.
This biofilm contains
exopolysaccharides
Extracellular polymeric substances (EPSs) are natural polymers of high molecular weight secreted by microorganisms into their environment. EPSs establish the functional and structural integrity of biofilms, and are considered the fundamental comp ...
that strengthen the bacterium's resistance to antibiotics and contribute to the bacteria's virulence. It is made up of a highly branched polysaccharide unit with one
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
, one
glucuronic acid
Glucuronic acid (from Greek γλεῦκος "''wine, must''" and οὖρον "''urine''") is a uronic acid that was first isolated from urine (hence the name). It is found in many gums such as gum arabic (c. 18%), xanthan, and kombucha tea and ...
, one
mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
, one
rhamnose
Rhamnose (Rha, Rham) is a naturally occurring deoxy sugar. It can be classified as either a methyl-pentose or a 6-deoxy-hexose. Rhamnose predominantly occurs in nature in its L-form as L-rhamnose (6-deoxy-L-mannose). This is unusual, since most o ...
, and three galactose molecules. This species in the ''Burkholderia cepacia'' complex has also created another polysaccharide with one 3-deoxy-d-''manno''-2-octulosonic acid and three galactose molecules. The biofilm exopolysaccharides act as a barrier to
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 ...
from human immune resistance systems, undermining the neutrophil defense action by inhibiting neutrophil
chemotaxis
Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...
and scavenging
reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
, which are bactericidal products produced by neutrophils to destroy bacteria.
Genome
''B. cenocepacias genome consists of three circular chromosomes and one
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
. Chromosome 1 contains 3.87 Mb, chromosome 2 contains 3.22 Mb, and chromosome 3 contains 0.88 Mb. The plasmid is approximately 0.09 Mb. Chromosome 3 has also been characterized as a large plasmid, or megaplasmid (pC3); unlike chromosomes 2 and 3, it does not contain essential
housekeeping gene
In molecular biology, housekeeping genes are typically constitutive genes that are required for the maintenance of basic cellular function, and are expressed in all cells of an organism under normal and patho-physiological conditions. Although ...
s, instead coding for accessory functions such as virulence and resistance to stress. In addition to the
multireplicon structure, the genome contains several
insertion sequence Insertion element (also known as an IS, an insertion sequence element, or an IS element) is a short DNA sequence that acts as a simple transposon, transposable element. Insertion sequences have two major characteristics: they are small relative to o ...
s and can rapidly mutate during infections, which contribute to ''B. cenocepacia''
's unique adaptability and ability to acquire diverse catabolic functions.
Environments
''Burkholderia cenocepacia'' has been found to thrive in primarily
microaerophilic
A microaerophile is a microorganism that requires environments containing lower levels of dioxygen than that are present in the atmosphere (i.e. < 21% O2; typically 2–10% O2) for optimal growth.[ A more re ...]
conditions, which consist of little to no oxygen.
Experimental studies conducted on the growth of ''B. cenocepacia'' in environments akin to the human lungs demonstrated the pathogen's increased success in microaerophilic environments over aerophilic settings.
In environments with little available iron such as the lungs of a cystic fibrosis patient, ''Burkholderia cenocepacia'' secretes
siderophore
Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is no ...
s, molecules that bind to iron and transport them to the bacteria.
Out of the four types of siderophores produced by the Bcc, ''B. cenocepacia'' produces three: ornibactin, pyochelin, and salicylic acid (SA). Ornibactin is the most important iron uptake system and can sustain the bacteria in an iron-deficient environment even without the production of functioning pyochelin or SA.
''B. cenocepacia'' has been demonstrated to colonize an array of ecological niches with diverse lifestyles. The ability to utilize a wide range of carbon sources accompanies the ability of Bcc species to be efficient with plant-growth promotion,
bioremediation
Bioremediation broadly refers to any process wherein a biological system (typically bacteria, microalgae, fungi, and plants), living or dead, is employed for removing environmental pollutants from air, water, soil, flue gasses, industrial effluent ...
, and biocontrol.
High potential of Bcc species, including ''B. cenocepacia'', as a biocontrol of plant-growth promoting agents has been demonstrated; however, the mechanisms that support this are not known.
In a bioremediation context, various Bcc strains are suggested to hold high potential to remediate environments contaminated with toxic compounds, including halogenated compounds.
In addition, ''B. cenocepacia'' has been found to exist in the rhizosphere, plants, soil, water, and animals.
In fact, it was found to have an
endophytic
An endophyte is an endosymbiont, often a bacterium or fungus, that lives within a plant for at least part of its life cycle without causing apparent disease. Endophytes are ubiquitous and have been found in all species of plants studied to date; h ...
lifestyle when recovered from plant material, indicating that it has endosymbiotic characteristics.
''Burkholderia cenocepacia'' was the dominant genomovar recovered in a study of bacteria in the rhizosphere of maize in China, pointing to endosymbiotic attributes with plants in soil.
However, ''B. cenocepacia'' also demonstrated
phytopathogenic
Plant pathology (also phytopathology) is the scientific study of diseases in plants caused by pathogens (infectious organisms) and environmental conditions (physiological factors). Organisms that cause infectious disease include fungi, oomyc ...
properties in causing fingertip rot in bananas.
Quorum sensing
One kind of cell-to-cell communication employed by ''B. cenocepacia'' is quorum sensing, which is the detection of fluctuations in cell density and usage of this information to regulate functions such as the formation of biofilms. Like other Gram-negative bacteria, ''B. cenocepacia'' produces acyl-homoserine lactones (AHLs), signaling molecules that in members of the ''Burkholderia cepacia'' complex specifically are encoded by two systems–the CepIR system, which is highly conserved in the Bcc, and the CciIR system.
The two AHL-mediated QS systems, CepIR and CciIR, regulate each other; the CepR protein is required for the transcription of the ''cciIR'' operon, while the CciR protein represses transcription of ''cepI''. The CciIR system can also negatively regulate the CepIR system through the production of C6-HSL, a type of AHL produced primarily by CciI proteins that inhibits the activity of CepR proteins.
The bacterium also uses cis-2-dodecenoic acid signals, which are known as ''Burkholderia'' diffusible signal factors (BDSF) because they were first identified in ''Burkholderia cenocepacia''.
Motility
''Burkholderia cenocepacia'' has the ability to swim and
swarm
Swarm behaviour, or swarming, is a collective behaviour exhibited by entities, particularly animals, of similar size which aggregate together, perhaps milling about the same spot or perhaps moving ''en masse'' or migrating in some direction. ...
inside the body. It has a polar flagella and produces a surfactant. These characteristics are necessary for the species to have motility in an agar medium. The surfactant produced by ''Burkholderia cenocepacia'' allows other pathogenic bacteria in the lungs to have motility. This means that the presence of ''Burkholderia cenocepacia'' is necessary for swarms of bacteria to coexist and cooperate in the lungs.
Pathogenicity
''Burkholderia cenocepacia'' is an
opportunistic pathogen
An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune ...
that commonly infects
immunocompromised
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 ...
patients, especially those with
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 ...
, and is often lethal.
In
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 ...
, it can cause "cepacia syndrome," which is characterized by a rapidly progressive fever, uncontrolled bronchopneumonia, weight loss, and in some cases, death. A review of ''B. cenocepacia'' in respiratory infections of cystic fibrosis patients stated that "one of the most threatening pathogens in
ystic fibrosisis ''Burkholderia cenocepacia'', a member of a bacterial group collectively referred to as the ''Burkholderia cepacia'' complex."
Twenty-four
small RNA
Small RNA (sRNA) are polymeric RNA molecules that are less than 200 nucleotides in length, and are usually non-coding
Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA ...
s were identified using RNA-binding properties of the
Hfq protein
The Hfq protein (also known as HF-I protein) encoded by the ''hfq'' gene was discovered in 1968 as an ''Escherichia coli'' host factor that was essential for replication of the bacteriophage Qβ. It is now clear that Hfq is an abundant bacterial RN ...
during the exponential growth phases. sRNAs identified in ''Burkholderia cenocepacia'' KC-0 were upregulated under iron depletion and oxidative stress.
''Burkholderia cenocepacia'' encodes two RNA chaperone proteins that assist sRNAs in binding to mRNA, Hfq and Hfq2. Both are required for maximum virulence and resistance against stressors such as acidic pH, high temperatures, osmotic stress, and oxidative stress. ''Burkholderia cenocepacia'' produces a toxin called double-stranded DNA deaminase A (DddA) made by the bacterium that converts DNA base cytosine to uracil.
Because uracil, which is not commonly found in DNA, behaves like a thymidine, the enzymes that replicate the cell’s DNA copy it as a thymidine, effectively converting a cytosine in the genome sequence to a thymidine. This has reportedly been used for the first
gene-editing of
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
– for which a team at the
Broad Institute
The Eli and Edythe L. Broad Institute of MIT and Harvard (IPA: , pronunciation respelling: ), often referred to as the Broad Institute, is a biomedical and genomic research center located in Cambridge, Massachusetts, Cambridge, Massachusetts, U ...
developed a new kind of CRISPR-free base editor, called DdCBE, using the toxin.
See also: ''
Burkholderia thailandensis'' sRNA
Antibiotic resistance
The structural factors that contribute to the antibiotic resistance of ''B. cenocepacia'' include: an impermeable outer membrane, an
efflux pump
In microbiology, efflux is the moving of a variety of different compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters. All micr ...
mechanism, and the production of a
beta-lactamase
Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems ...
. This microbe challenges infection prevention as it is resistant to some disinfectants and antiseptics. It can survive on surfaces, including human skin and mucosal surfaces for an extended period of time.
Virulence
Virulence in ''Burkholderia cenocepacia'' is widely attributed to biofilm formation, siderophore production, and QS signaling - each of which affect how the species adapts in various environmental conditions.
''B. cenocepacia''
's ability to adapt to host environments contributes to chronic opportunistic infections and bacterial persistence.
Several strains are noted as "epidemic strains" due to increased transmission capability and patient-to-patient transmission.
The ET12 strain was found to have a "cable pilus," which enables greater adhesion of bacteria to epithelial cells.
In human airway epithelial cells, the invasion pathway utilized by the BC-7 strain of ''B. cenocepacia'' is largely the result of the strain's biofilm formation. In general, both environmental and clinical strains of ''B. cenocepacia'' are able to form biofilms; however, the ability to do so is greater in clinical strains. The H111 strain of ''Burkholderia cenocepacia'' forms biofilms on pea roots, for example. Quorum signaling (QS) affects the ability of ''B. cenocepacia'' to develop biofilms, in addition to the motility abilities.
In addition, quorum signaling controls a variety of cellular processes, such as extracellular proteases, polygalacturonase, and the production of siderophores.
Cystic fibrosis
''Burkholderia cenocepacia'' is one of over twenty bacteria in the ''Burkholderia cepacia'' complex (Bcc), and among these species, it is a dominant bacteria associated with
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 ...
. ''B. cenocepacia'' has such high transmissibility that it has spread across continents, including Europe and Canada, between cystic fibrosis patients at epidemic levels.
Patients with cystic fibrosis are threatened most by opportunistic pathogens.
Based on the distribution of Bcc species in sample cystic fibrosis patient populations, ''B. cenocepacia'' claims between 45.6% and 91.8% of all infections caused by the Bcc complex.
Compared to other infectious agents found in cystic fibrosis patients, the Bcc complex demonstrates the greatest association with increased
morbidity
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
and
mortality
Mortality is the state of being mortal, or susceptible to death; the opposite of immortality.
Mortality may also refer to:
* Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...
.
Compared to other species in the Bcc complex, ''B. cenocepacia'' was shown to possibly accelerate BMI decline and
FEV1 (forced expiration) at the greatest rate, leading to worse prognoses for cystic fibrosis patients.
The Bcc complex consists of
genomovars, which are species characterized to be phylogenetically close, though distinct from each other.
In cystic fibrosis infections, it is common for only one of the known nine genomovars to induce an infection.
Overall, in patients with cystic fibrosis, the genomovar status of the Bcc has a significant influence on the success of clinical interventions, as well as the temporal progression of the condition.
Applications
Biotechnology
Given the opportunistic nature of the Bcc complex and ''B. cenocepacia'', the severity of respiratory infections is considered to be a significant conflict for applications in biotechnology.
Agriculture
To increase soil health,
plant-growth promoting rhizobacteria
Rhizobacteria are root-associated bacteria that can have a detrimental (parasitic varieties), neutral or beneficial effect on plant growth. The name comes from the Greek ''rhiza'', meaning root. The term usually refers to bacteria that form symbio ...
(PGPR) are used in the agricultural industry to create bio-organic fertilizers.
A current challenge is identifying which bacterial species are optimal at stimulating plant growth in bio-organic fertilizers. Creating bio-organic fertilizers has been increasingly successful with the use of plant-growth promoting rhizobacteria mixed with organic substrates.
''B. cenocepacia'' has various PGPR traits like phosphate solubilization that make it well-suited to promote growth. With the addition of solid-state fermentation technology, creating bio-organic fertilizers was highly successful by incorporating ''B. cenocepacia'' with high protein content agricultural wastes.
References
External links
*
Type strain of ''Burkholderia cenocepacia'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q4810500
Burkholderiaceae
Bacteria described in 2003