Dehalococcoides

Last updated

Dehalococcoides
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Bacteria
Phylum: Chloroflexota
Class: Dehalococcoidia
Order: Dehalococcoidales
Family: Dehalococcoidaceae
Genus: Dehalococcoides
Löffler et al. 2013 [1]
Type species
Dehalococcoides mccartyi
Löffler et al. 2013
Species
  • D. mccartyiLöffler et al. 2013
Synonyms
  • "Dehalococcoides" Maymo-Gatell et al. 1997
  • "Dehalococcoides ethenogenes" Maymo-Gatell et al. 1997

Dehalococcoides is a genus of bacteria within class Dehalococcoidia that obtain energy via the oxidation of hydrogen and subsequent reductive dehalogenation of halogenated organic compounds in a mode of anaerobic respiration called organohalide respiration. [2] They are well known for their great potential to remediate halogenated ethenes and aromatics. They are the only bacteria known to transform highly chlorinated dioxins, PCBs. In addition, they are the only known bacteria to transform tetrachloroethene (perchloroethene, PCE) to ethene.

Contents

Microbiology

The first member of the genus Dehalococcoides was described in 1997 as Dehalococcoides ethenogenes strain 195 (nom. inval.). Additional Dehalococcoides members were later described as strains CBDB1, [3] BAV1, FL2, VS, and GT. In 2012 all yet-isolated Dehalococcoides strains were summarized under the new taxonomic name D. mccartyi , with strain 195 as the type strain. [4]

GTDB release 202 clusters the genus into three species, all labeled Dehalococcoides mccartyi in their NCBI accession. [5]

Activities

Dehalococcoides are obligately organohalide-respiring bacteria, [4] meaning that they can only grow by using halogenated compounds as electron acceptors. Currently, hydrogen (H2) is often regarded as the only known electron donor to support growth of dehalococcoides bacteria. [6] [7] [8] However, studies have shown that using various electron donors such as formate, [9] and methyl viologen, [7] have also been effective in promoting growth for various species of dehalococcoides. In order to perform reductive dehalogenation processes, electrons are transferred from electron donors through dehydrogenases, and ultimately used to reduce halogenated compounds, [4] many of which are human-synthesized chemicals acting as pollutants. [10] Furthermore, it has been shown that a majority of reductive dehalogenase activities lie within the extracellular and membranous components of D. ethenogenes, indicating that dechlorination processes may function semi-independently from intracellular systems. [7] Currently, all known dehalococcoides strains require acetate for producing cellular material, however, the underlying mechanisms are not well understood as they appear to lack fundamental enzymes that complete biosynthesis cycles found in other organisms. [8]

Dehalococcoides can transform many persistent compounds. This includes tetrachloroethylene (PCE) and trichloroethylene (TCE) which are transformed to ethylene, and chlorinated dioxins, vinyl chloride, benzenes, polychlorinated biphenyls (PCBs), phenols and many other aromatic contaminants. [11] [12] [13]

Applications

Dehalococcoides can uniquely transform many highly toxic and/or persistent compounds that are not transformed by any other known bacteria, in addition to halogenated compounds that other common organohalide respirers use. [10] [14] For example, common compounds such as chlorinated dioxins, benzenes, PCBs, phenols and many other aromatic substrates can be reduced into less harmful chemical forms. [10] However, dehalococcoides are currently the only known dechlorinating bacteria with the unique ability to degrade the highly recalcitrant, tetrachloroethene (PCE) and Trichloroethylene (TCE) compounds into more suitable for environmental conditions, and thus used in bioremediation. [10] [15] [9] Their capacity to grow by using contaminants allows them to proliferate in contaminated soil or groundwater, offering promise for in situ decontamination efforts.

The process of transforming halogenated pollutants to non-halogenated compounds involves different reductive enzymes. D. mccartyi strain BAV1 is able to reduce vinyl chloride, a contaminant that usually originates from landfills, to ethene by using a special vinyl chloride reductase thought to be coded for by the bvcA gene. [16] A chlorobenzene reductive dehalogenase has also been identified in the strain CBDB1. [17]

Several companies worldwide now use Dehalococcoides-containing mixed cultures in commercial remediation efforts. In mixed cultures, other bacteria present can augment the dehalogenation process by producing metabolic products that can be used by Dehalococcoides and others involved in the degradation process. [11] [18] For example, Dehalococcoides sp. strain WL can work alongside Dehalobacter in a step-wise manner to degrade vinyl chloride: Dehalobacter converts 1,1,2-TCA to vinyl chloride, which is subsequently degraded by Dehalococcoides. [19] Also, the addition of electron acceptors is needed – they are converted to hydrogen in situ by other bacteria present, which can then be used as an electron source by Dehalococcoides. [14] [11] MEAL (a methanol, ethanol, acetate, and lactate mixture) is documented to have been used as substrate. [20] In the US, BAV1 was patented for the in situ reductive dechlorination of vinyl chlorides and dichloroethylenes in 2007. [21] D. mccartyi in high-density dechlorinating bioflocs have also been used in ex situ bioremediation. [22]

Although dehalococcoides have been shown to reduce contaminants such as PCE and TCE, it appears that individual species have various dechlorinating capabilities which contributes to the degree that these compounds are reduced. This could have implications on the effects of bioremediation tactics. [15] For example, particular strains of dehalococcoides have shown preference to produce more soluble, intermediates such as 1,2–dichloroethene isomers and vinyl chloride that contrasts against bioremediation goals, primarily due to their harmful nature. [6] [10] Therefore, an important aspect of current bioremediation tactics involves the use of multiple dechlorinating organisms to promote symbiotic relationships within a mixed culture to ensure complete reduction to ethene. [15] As a result, studies have focused upon metabolic pathways and environmental factors that regulate reductive dehalogenative processes in order to better implement dehalococcoides for bioremediation tactics. [10]

However, not all members of Dehalococcoides can reduce all halogenated contaminants. Certain strains cannot use PCE or TCE as electron acceptors (e.g. CBDB1) and some cannot use vinyl chloride as an electron acceptor (e.g. FL2). [16] D. mccartyi strains 195 and SFB93 are inhibited by high concentrations of acetylene (which builds up in contaminated groundwater sites as a result of TCE degradation) via changes in gene expression that likely disrupt normal electron transport chain function. [11] Even when D. mccartyi strains work well to turn toxic chemicals into harmless ones, treatment times range from months to decades. [23] When selecting Dehalococcoides strains for bioremediation use, it is important to consider their metabolic capabilities and their sensitivities to different chemicals.

In 2022, the United States National Aeronautics and Space Administration (NASA) co-funded a US$1.9 million multi-year project with Arizona State University, the University of Arizona, and the Florida Institute of Technology to reduce perchlorates (such as those found in the regolith of Mars) to a useful form of soil for growing plants. [23]

Genomes

Several strains of Dehalococcoides sp. has been sequenced. [24] [25] [26] They contain between 14 and 36 reductive dehalogenase homologous (rdh) operons each consisting of a gene for the active dehalogenases (rdhA) and a gene for a putative membrane anchor (rdhB). Most rdh-operons in Dehalococcoides genomes are preceded by a regulator gene, either of the marR-type (rdhR) or a two-component system (rdhST). Dehalococcoides have very small genomes of about 1.4–1.5 Mio base pairs. This is one of the smallest values for free-living organisms.

Biochemistry

Dehalococcoides strains do not seem to encode quinones but respire with a novel protein-bound electron transport chain. [27]

See also

Related Research Articles

<span class="mw-page-title-main">Bioremediation</span> Process used to treat contaminated media such as water and soil

Bioremediation broadly refers to any process wherein a biological system, living or dead, is employed for removing environmental pollutants from air, water, soil, flue gasses, industrial effluents etc., in natural or artificial settings. The natural ability of organisms to adsorb, accumulate, and degrade common and emerging pollutants has attracted the use of biological resources in treatment of contaminated environment. In comparison to conventional physicochemical treatment methods bioremediation may offer advantages as it aims to be sustainable, eco-friendly, cheap, and scalable.

Anaerobic respiration is respiration using electron acceptors other than molecular oxygen (O2). Although oxygen is not the final electron acceptor, the process still uses a respiratory electron transport chain.

In organochlorine chemistry, reductive dechlorination describes any chemical reaction which cleaves the covalent bond between carbon and chlorine via reductants, to release chloride ions. Many modalities have been implemented, depending on the application. Reductive dechlorination is often applied to remediation of chlorinated pesticides or dry cleaning solvents. It is also used occasionally in the synthesis of organic compounds, e.g. as pharmaceuticals.

Halocarbon compounds are chemical compounds in which one or more carbon atoms are linked by covalent bonds with one or more halogen atoms resulting in the formation of organofluorine compounds, organochlorine compounds, organobromine compounds, and organoiodine compounds. Chlorine halocarbons are the most common and are called organochlorides.

Biological augmentation is the addition of archaea or bacterial cultures required to speed up the rate of degradation of a contaminant. Organisms that originate from contaminated areas may already be able to break down waste, but perhaps inefficiently and slowly.

<i>Geobacter</i> Genus of anaerobic bacteria found in soil

Geobacter is a genus of bacteria. Geobacter species are anaerobic respiration bacterial species which have capabilities that make them useful in bioremediation. Geobacter was found to be the first organism with the ability to oxidize organic compounds and metals, including iron, radioactive metals, and petroleum compounds into environmentally benign carbon dioxide while using iron oxide or other available metals as electron acceptors. Geobacter species are also found to be able to respire upon a graphite electrode. They have been found in anaerobic conditions in soils and aquatic sediment.

Cometabolism is defined as the simultaneous degradation of two compounds, in which the degradation of the second compound depends on the presence of the first compound. This is in contrast to simultaneous catabolism, where each substrate is catabolized concomitantly by different enzymes. Cometabolism occurs when an enzyme produced by an organism to catalyze the degradation of its growth-substrate to derive energy and carbon from it is also capable of degrading additional compounds. The fortuitous degradation of these additional compounds does not support the growth of the bacteria, and some of these compounds can even be toxic in certain concentrations to the bacteria.

Organohalide respiration (OHR) (previously named halorespiration or dehalorespiration) is the use of halogenated compounds as terminal electron acceptors in anaerobic respiration. Organohalide respiration can play a part in microbial biodegradation. The most common substrates are chlorinated aliphatics (PCE, TCE, chloroform) and chlorinated phenols. Organohalide-respiring bacteria are highly diverse. This trait is found in some Campylobacterota, Thermodesulfobacteriota, Chloroflexota (green nonsulfur bacteria), low G+C gram positive Clostridia, and ultramicrobacteria.

Microbial biodegradation is the use of bioremediation and biotransformation methods to harness the naturally occurring ability of microbial xenobiotic metabolism to degrade, transform or accumulate environmental pollutants, including hydrocarbons, polychlorinated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs), heterocyclic compounds, pharmaceutical substances, radionuclides and metals.

In enzymology, a tetrachloroethene reductive dehalogenase is an enzyme that catalyzes the chemical reaction. This is a member of reductive dehalogenase enzyme family.

A dehalogenase is a type of enzyme that catalyzes the removal of a halogen atom from a substrate.

In situ chemical reduction (ISCR) is a type of environmental remediation technique used for soil and/or groundwater remediation to reduce the concentrations of targeted environmental contaminants to acceptable levels. It is the mirror process of In Situ Chemical Oxidation (ISCO). ISCR is usually applied in the environment by injecting chemically reductive additives in liquid form into the contaminated area or placing a solid medium of chemical reductants in the path of a contaminant plume. It can be used to remediate a variety of organic compounds, including some that are resistant to natural degradation.

Dehalococcoidia is a class of Chloroflexota, a phylum of Bacteria. It is also known as the DHC group.

Dehalobacter restrictus is a species of bacteria in the phylum Bacillota. It is strictly anaerobic and reductively dechlorinates tetra- and trichloroethene. It does not form spores; it is a small, gram-positive rod with one lateral flagellum. PER-K23 is its type strain.

Desulfitobacterium dehalogenans is a species of bacteria. They are facultative organohalide respiring bacteria capable of reductively dechlorinating chlorophenolic compounds and tetrachloroethene. They are anaerobic, motile, Gram-positive and rod-shaped bacteria capable of utilizing a wide range of electron donors and acceptors. The type strain JW/IU-DCT, DSM 9161, NCBi taxonomy ID 756499.

Desulfitobacterium hafniense is a species of gram positive bacteria, its type strain is DCB-2T..

Dehalogenimonas lykanthroporepellens is an anaerobic, Gram-negative bacteria in the phylum Chloroflexota isolated from a Superfund site in Baton Rouge, Louisiana. It is useful in bioremediation for its ability to reductively dehalogenate chlorinated alkanes.

Adsorbable organic halides (AOX) is a measure of the organic halogen load at a sampling site such as soil from a land fill, water, or sewage waste. The procedure measures chlorine, bromine, and iodine as equivalent halogens, but does not measure fluorine levels in the sample.

Polychorinated biphenyls, or PCBs, are a type of chemical that was widely used in the 1960s and 1970s, and which are a contamination source of soil and water. They are fairly stable and therefore persistent in the environment. Bioremediation of PCBs is the use of microorganisms to degrade PCBs from contaminated sites, relying on multiple microorganisms' co-metabolism. Anaerobic microorganisms dechlorinate PCBs first, and other microorganisms that are capable of doing BH pathway can break down the dechlorinated PCBs to usable intermediates like acyl-CoA or carbon dioxide. If no BH pathway-capable microorganisms are present, dechlorinated PCBs can be mineralized with help of fungi and plants. However, there are multiple limiting factors for this co-metabolism.

Reductive dehaholagenses (EC 1.97.1.8) are a group of enzymes utilized in organohalide respiring bacteria. These enzymes are mostly attached to the periplasmic side of the cytoplasmic membrane and play a central role in energy-conserving respiratory process for organohalide respiring bacteria by reducing organohalides. During such reductive dehalogenation reaction, organohalides are used as terminal electron acceptors. They catalyze the following general reactions:

References

  1. ↑ Löffler FE, Yan J, Ritalahti KM, Adrian L, Edwards EA, Konstantinidis KT, Muller JA, Fullerton H, Zinder SH, Spormann AM. (2013). "Dehalococcoides mccartyi gen. nov., sp. nov., obligately organohalide-respiring anaerobic bacteria relevant to halogen cycling and bioremediation, belong to a novel bacterial class, Dehalococcoidia classis nov., order Dehalococcoidales ord. nov. and family Dehalococcoidaceae fam. nov., within the phylum Chloroflexi". Int J Syst Evol Microbiol. 63 (Pt 2): 625–635. doi:10.1099/ijs.0.034926-0. PMID   22544797.
  2. ↑ "Dehalococcoides". NCIB Taxonomy Browser.
  3. ↑ Adrian L, Szewzyk U, Wecke J, Görisch H (2000). "Bacterial dehalorespiration with chlorinated benzenes". Nature. 408 (6812): 580–583. Bibcode:2000Natur.408..580A. doi:10.1038/35046063. PMID   11117744. S2CID   4350003.
  4. 1 2 3 Loffler, F. E.; Yan, J.; Ritalahti, K. M.; Adrian, L.; Edwards, E. A.; Konstantinidis, K. T.; Muller, J. A.; Fullerton, H.; Zinder, S. H.; Spormann, A. M. (2012). "Dehalococcoides mccartyi gen. nov., sp. nov., obligately organohalide-respiring anaerobic bacteria relevant to halogen cycling and bioremediation, belong to a novel bacterial class, Dehalococcoidia classis nov., order Dehalococcoidales ord. nov. and family Dehalococcoidaceae fam. nov., within the phylum Chloroflexi". International Journal of Systematic and Evolutionary Microbiology. 63 (Pt 2): 625–635. doi:10.1099/ijs.0.034926-0. ISSN   1466-5026. PMID   22544797.
  5. ↑ "GTDB - Tree". gtdb.ecogenomic.org.
  6. 1 2 Cheng, Dan; He, Jianzhong (15 September 2009). "Isolation and Characterization of "Dehalococcoides" sp. Strain MB, Which Dechlorinates Tetrachloroethene to trans-1,2-Dichloroethene". Applied and Environmental Microbiology. 75 (18): 5910–5918. Bibcode:2009ApEnM..75.5910C. doi:10.1128/AEM.00767-09. PMC   2747852 . PMID   19633106.
  7. 1 2 3 Nijenhuis, Ivonne; Zinder, Stephen H. (1 March 2005). "Characterization of Hydrogenase and Reductive Dehalogenase Activities of Dehalococcoides ethenogenes Strain 195". Applied and Environmental Microbiology. 71 (3): 1664–1667. Bibcode:2005ApEnM..71.1664N. doi:10.1128/AEM.71.3.1664-1667.2005. PMC   1065153 . PMID   15746376.
  8. 1 2 Tang, Yinjie J.; Yi, Shan; Zhuang, Wei-Qin; Zinder, Stephen H.; Keasling, Jay D.; Alvarez-Cohen, Lisa (15 August 2009). "Investigation of Carbon Metabolism in "Dehalococcoides ethenogenes" Strain 195 by Use of Isotopomer and Transcriptomic Analyses". Journal of Bacteriology. 191 (16): 5224–5231. doi:10.1128/JB.00085-09. PMC   2725585 . PMID   19525347.
  9. 1 2 Mayer-Blackwell, Koshlan; Azizian, Mohammad F.; Green, Jennifer K.; Spormann, Alfred M.; Semprini, Lewis (7 February 2017). "Survival of Vinyl Chloride Respiring dehalococcoides mccartyi under Long-Term Electron Donor Limitation". Environmental Science & Technology. 51 (3): 1635–1642. Bibcode:2017EnST...51.1635M. doi:10.1021/acs.est.6b05050. PMID   28002948.
  10. 1 2 3 4 5 6 Maphosa, Farai; Lieten, Shakti H.; Dinkla, Inez; Stams, Alfons J.; Smidt, Hauke; Fennell, Donna E. (2 October 2012). "Ecogenomics of microbial communities in bioremediation of chlorinated contaminated sites". Frontiers in Microbiology. 3: 351. doi: 10.3389/fmicb.2012.00351 . PMC   3462421 . PMID   23060869.
  11. 1 2 3 4 Mao, Xinwei; Oremland, Ronald S.; Liu, Tong; Gushgari, Sara; Landers, Abigail A.; Baesman, Shaun M.; Alvarez-Cohen, Lisa (2017-02-21). "Acetylene Fuels TCE Reductive Dechlorination by Defined Dehalococcoides/Pelobacter Consortia". Environmental Science & Technology. 51 (4): 2366–2372. Bibcode:2017EnST...51.2366M. doi:10.1021/acs.est.6b05770. ISSN   0013-936X. PMC   6436540 . PMID   28075122.
  12. ↑ Lu, Gui-Ning; Tao, Xue-Qin; Huang, Weilin; Dang, Zhi; Li, Zhong; Liu, Cong-Qiang (2010). "Dechlorination pathways of diverse chlorinated aromatic pollutants conducted by Dehalococcoides sp. strain CBDB1". Science of the Total Environment. 408 (12): 2549–2554. Bibcode:2010ScTEn.408.2549L. doi:10.1016/j.scitotenv.2010.03.003. PMID   20346484.
  13. ↑ Fennell, Donna E.; Nijenhuis, Ivonne; Wilson, Susan F.; Zinder, Stephen H.; Häggblom, Max M. (2004-04-01). "Dehalococcoides ethenogenes Strain 195 Reductively Dechlorinates Diverse Chlorinated Aromatic Pollutants". Environmental Science & Technology. 38 (7): 2075–2081. Bibcode:2004EnST...38.2075F. doi:10.1021/es034989b. ISSN   0013-936X. PMID   15112809.
  14. 1 2 Maymó-Gatell, Xavier; Chien, Yueh-tyng; Gossett, James M.; Zinder, Stephen H. (1997-06-06). "Isolation of a Bacterium That Reductively Dechlorinates Tetrachloroethene to Ethene". Science. 276 (5318): 1568–1571. doi:10.1126/science.276.5318.1568. ISSN   0036-8075. PMID   9171062.
  15. 1 2 3 Grostern, Ariel; Edwards, Elizabeth A. (2006). "Growth of Dehalobacter and Dehalococcoides spp. during Degradation of Chlorinated Ethanes". Applied and Environmental Microbiology. 72 (1): 428–436. Bibcode:2006ApEnM..72..428G. doi:10.1128/AEM.72.1.428-436.2006. PMC   1352275 . PMID   16391074.
  16. 1 2 Krajmalnik-Brown, Rosa; Hölscher, Tina; Thomson, Ivy N.; Saunders, F. Michael; Ritalahti, Kirsti M.; Löffler, Frank E. (2004-10-01). "Genetic Identification of a Putative Vinyl Chloride Reductase in Dehalococcoides sp. Strain BAV1". Applied and Environmental Microbiology. 70 (10): 6347–6351. Bibcode:2004ApEnM..70.6347K. doi:10.1128/aem.70.10.6347-6351.2004. ISSN   0099-2240. PMC   522117 . PMID   15466590.
  17. ↑ Adrian, Lorenz; Rahnenführer, Jan; Gobom, Johan; Hölscher, Tina (2007-12-01). "Identification of a Chlorobenzene Reductive Dehalogenase in Dehalococcoides sp. Strain CBDB1". Applied and Environmental Microbiology. 73 (23): 7717–7724. Bibcode:2007ApEnM..73.7717A. doi:10.1128/aem.01649-07. ISSN   0099-2240. PMC   2168065 . PMID   17933933.
  18. ↑ Duhamel, Melanie; Edwards, Elizabeth A. (2006-12-01). "Microbial composition of chlorinated ethene-degrading cultures dominated by Dehalococcoides". FEMS Microbiology Ecology. 58 (3): 538–549. doi: 10.1111/j.1574-6941.2006.00191.x . ISSN   0168-6496. PMID   17117995.
  19. ↑ Grostern, Ariel; Edwards, Elizabeth A. (2006-01-01). "Growth of Dehalobacter and Dehalococcoides spp. during Degradation of Chlorinated Ethanes". Applied and Environmental Microbiology. 72 (1): 428–436. Bibcode:2006ApEnM..72..428G. doi:10.1128/aem.72.1.428-436.2006. ISSN   0099-2240. PMC   1352275 . PMID   16391074.
  20. ↑ McKinsey, P.C. (February 20, 2003). "Bioremediation of Trichloroethylene-Contaminated Sediments Augmented with a Dehalococcoides Consortia". Retrieved October 8, 2017.
  21. ↑ Loeffler, Frank (May 3, 2007). "United States Patent Application 20070099284". Archived from the original on 2018-08-27. Retrieved 2017-10-09.
  22. ↑ Fajardo-Williams, Devyn (2015). "Coupling Bioflocculation of Dehalococcoides to High-Dechlorination Rates for Ex situ and In situ Bioremediation". ProQuest. ProQuest   1718184775.
  23. 1 2 Brown, David W. (November 2024). "Red Mars, green Mars". MIT Technology Review. 127 (6). Massachusetts Institute of Technology: 24–26.
  24. ↑ Kube, M.; Beck, A.; Zinder, SH.; Kuhl, H.; Reinhardt, R.; Adrian, L. (Oct 2005). "Genome sequence of the chlorinated compound-respiring bacterium Dehalococcoides species strain CBDB1". Nat Biotechnol. 23 (10): 1269–73. doi: 10.1038/nbt1131 . PMID   16116419.
  25. ↑ Seshadri, R.; Adrian, L.; Fouts, DE.; Eisen, JA.; Phillippy, AM.; Methe, BA.; Ward, NL.; Nelson, WC.; et al. (Jan 2005). "Genome sequence of the PCE-dechlorinating bacterium Dehalococcoides ethenogenes". Science. 307 (5706): 105–8. Bibcode:2005Sci...307..105S. doi:10.1126/science.1102226. PMID   15637277. S2CID   15601443.
  26. ↑ Pöritz, M.; Goris, T.; Wubet, T.; Tarkka, MT.; Buscot, F.; Nijenhuis, I.; Lechner, U.; Adrian, L. (Jun 2013). "Genome sequences of two dehalogenation specialists – Dehalococcoides mccartyi strains BTF08 and DCMB5 enriched from the highly polluted Bitterfeld region". FEMS Microbiol Lett. 343 (2): 101–4. doi: 10.1111/1574-6968.12160 . PMID   23600617.
  27. ↑ Kublik, Anja; Deobald, Darja; Hartwig, Stefanie; Schiffmann, Christian L.; Andrades, Adarelys; von Bergen, Martin; Sawers, R. Gary; Adrian, Lorenz (2016-09-01). "Identification of a multi-protein reductive dehalogenase complex in Dehalococcoides mccartyi strain CBDB1 suggests a protein-dependent respiratory electron transport chain obviating quinone involvement". Environmental Microbiology. 18 (9): 3044–3056. doi:10.1111/1462-2920.13200. ISSN   1462-2920. PMID   26718631.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.