Burkholderia cenocepacia

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.[1] 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 infections in immunocompromised patients, such as those with cystic fibrosis or chronic granulomatous disease.[2] Burkholderia cenocepacia may also cause disease in plants, such as in onions[3][4] and bananas.[5] Additionally, some strains serve as plant growth-promoting rhizobacteria.[6]

Burkholderia cenocepacia
Electron micrograph of Burkholderia cepacia
Scientific classification
Domain: Bacteria
Phylum: Pseudomonadota
Class: Betaproteobacteria
Order: Burkholderiales
Family: Burkholderiaceae
Genus: Burkholderia
Species:
B. cenocepacia
Binomial name
Burkholderia cenocepacia
Vandamme et al. 2003

Taxonomy

Within the Burkholderia genus, the Burkholderia cepacia complex contains over 20 related species that cause opportunistic infections and possess antibiotic resistance.[7] Burkholderia cepacia was originally defined as a single species, but it is now one of several species in the Bcc.[8] 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.[9] 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.[9] 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.[5][10]

Pathogenicity

Burkholderia cenocepacia is an opportunistic pathogen that commonly infects immunocompromised patients, especially those with cystic fibrosis, and is often lethal.[11] In cystic fibrosis, 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 [cystic fibrosis] is Burkholderia cenocepacia, a member of a bacterial group collectively referred to as the Burkholderia cepacia complex.[12] Twenty-four small RNAs were identified using RNA-binding properties of the Hfq protein during the exponential growth phases.[13] sRNAs identified in Burkholderia cenocepacia KC-0 were upregulated under iron depletion and oxidative stress.[14] In Seattle, a team led by microbiologist Joseph Mougous at the University of Washington had discovered a strange enzyme (a toxin called DddA) made by the bacterium Burkholderia cenocepacia — and when it encountered the DNA base C, it converted it to a U. Because U, which is not commonly found in DNA, behaves like a T, the enzymes that replicate the cell’s DNA copy it as a T, effectively converting a C in the genome sequence to a T. This has reportedly been used for the first gene-editing of mitochondria – for which a team at the Broad Institute developed a new kind of CRISPR-free base editor, called DdCBE, using the toxin.[15][16][17][18]

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 mechanism, and the production of a beta-lactamase.[19] 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.[20]

Cystic fibrosis

Burkholderia cenocepacia is one of the seventeen dominant bacteria attributed with cystic fibrosis. B. cenocepacia has such high transmissibility that it has spread across continents, most notably Europe and Canada, between cystic fibrosis patients at epidemic levels.[21] Patients with cystic fibrosis are threatened most by opportunistic pathogens; in this case, B. cenocepacia is a member of the Burkholderia cepacia complex (Bcc).[21] 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.[21] Compared to other infectious agents found in cystic fibrosis patients, the Bcc complex demonstrates the greatest association with increased morbidity and mortality.[22] Among the seventeen bacteria that comprise 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.[22]

Microbiology

The strong environmental protection response of B. cenocepacia is attributed to the biofilm formed by groups of the organism.[23] This biofilm contains exopolysaccharides that strengthen the bacterium's resistance to antibiotics. It is made up of a highly branched polysaccharide unit with one glucose, one glucuronic acid, one mannose, one rhamnose, 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.[24] The biofilm exopolysaccharides acted as a barrier to neutrophils from human immune resistance systems, undermining the neutrophil defense action by inhibiting chemotaxis and reducing the production of reactive oxygen species.[25]

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.[26] 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.[26][27] 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.[28]

Motility

Burkholderia cenocepacia has the ability to swim and swarm 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 Burkolderia cenocepacia is necessary for swarms of bacteria to coexist and cooperate in the lungs.[29]

Applications

Agriculture

To increase soil health, plant-growth promoting rhizobacteria (PGPR) are used in the agricultural industry to create bio-organic fertilizers.[30] 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.[30] 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.[30]

References
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