Abstract
Introduction
Bongkrekic acid (BA) has a unique mechanism of toxicity among the mitochondrial toxins: it inhibits adenine nucleotide translocase (ANT) rather than the electron transport chain. Bongkrekic acid is produced by the bacterium Burkholderia gladioli pathovar cocovenenans (B. cocovenenans) which has been implicated in outbreaks of food-borne illness involving coconut- and corn-based products in Indonesia and China. Our objective was to summarize what is known about the epidemiology, exposure sources, toxicokinetics, pathophysiology, clinical presentation, and diagnosis and treatment of human BA poisoning.
Methods
We searched MEDLINE (1946 to present), EMBASE (1947 to present), SCOPUS, The Indonesia Publication Index (http://id.portalgaruda.org/), ToxNet, book chapters, Google searches, Pro-MED alerts, and references from previously published journal articles. We identified a total of 109 references which were reviewed. Of those, 29 (26 %) had relevant information and were included. Bongkrekic acid is a heat-stable, highly unsaturated tricarboxylic fatty acid with a molecular weight of 486 kDa. Outbreaks have been reported from Indonesia, China, and more recently in Mozambique. Very little is known about the toxicokinetics of BA. Bongkrekic acid produces its toxic effects by inhibiting mitochondrial (ANT). ANT can also alter cellular apoptosis. Signs and symptoms in humans are similar to the clinical findings from other mitochondrial poisons, but they vary in severity and time course. Management of patients is symptomatic and supportive.
Conclusions
Bongkrekic acid is a mitochondrial ANT toxin and is reported primarily in outbreaks of food-borne poisoning involving coconut and corn. It should be considered in outbreaks of food-borne illness when signs and symptoms manifest involving the liver, brain, and kidneys and when coconut- or corn-based foods are implicated.
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References
Garcia RA, Hotchkiss JH, Steinkraus KH. The effect of lipids on bongkrekic (bongkrek) acid toxin production by Burkholderia cocovenenans in coconut media. Food Addit Contam. 1999;16(2):63–9.
Meng Z, Li Z, Jin J, Zhang Y, Liu X, Yiang X, et al. Studies on fermented corn flour poisoning in rural areas of China. I. Epidemiology, clinical manifestations, and pathology. Biomed Environ Sci. 1998;1(1):101–4.
Ramzy A. 5 die from food poisoning from southern Chinese snack. The New York Times. 2014. http://sinosphere.blogs.nytimes.com/2014/07/04/5-die-in-food-poisoning-from-southern-chinese-snack/?_r=0. Accessed 01 Oct 2015.
Cox J, Kartadarma E, Buckle KA. Burkholderia cocovenenans. In: Hocking AD, editor. Foodborne microorganisms of public health significance. 6th ed. Sydney: Australian Institute of Food Science & Technology; 1997. p. 521–30.
Arbianto P. Bongkrek food poisoning. In: Java: Proceedings of the Fifth International Conference on Global Impacts of Applied Microbiology; 1979. pp. 371–4.
Ko SD. Growth and toxin production of Pseudomonas cocovenenans, the so-called “bongkrek bacteria.”. ASEAN Food J. 1985;1:78.
Buckle KA, Kartadarma E. Inhibition of bongkrek acid and toxoflavin production in Tempe bongkrek containing Pseudomonas cocovenenans. J Appl Bacteriol. 1990;68:571–6.
ProMED-mail. Burkholderia cocovenenans foodborne illness—Indonesia (Central Java). ProMED-mail 2007; 02 Aug. 20070802.2493. http://www.promedmail.org. Accessed 14 Aug 2015.
Novit E. Suspected tempe poisoning, 1 killed and 3 treated [in Indonesian]. Okezone.com. 2013. http://news.okezone.com/read/2013/02/15/513/762277/diduga-keracunan-tempe-1-orang-tewas-3-dirawat. Accessed 25 Oct 2015.
Shen Y, Liu J, Huang Z. Epidemiological analysis of food poisoning due to contamination of fermented flour with Pseudomonas cocovenenans subsp, farino fermentans in Guangxi [in Mandarin]. China Trop Med. 2007;7(5):814–5.
Chengdu Center for Disease Control and Prevention. Beware of summer production of “hanging syrup cake.” China Pharmaceutical News; 2014.
ProMED-mail. Contaminated beer, fatal—Mozambique (03): (TE) Burkholderia gladioli pv cocovenenans toxin. ProMED-mail 2015: 20151109.3778425. http://www.promedmail.org/post/3778425. Accessed 09 Nov 2015.
Lynch KH, Dennis JJ. Burkholderia. In: Liu D, editor. Molecular detection of foodborne pathogens. Boca Raton: CRC Press; 2009. p. 331–43.
Deshpande SS. Bongkrek toxins. In: Handbook of food toxicology. New York: Marcel Decker; 2002. p. 661–2.
Moebius N, Ross C, Scherlach K, Rohm B, Roth M, Hertweck C. Biosynthesis of the respiratory toxin bongkrekic acid in the pathogenic bacterium Burkholderia gladioli. Chem Biol. 2012;19(9):1164–74.
Hu WJ, Zhang GS, Chu FS, Meng HD, Meng ZH. Purification and partial characterization of flavotoxin A. Appl Environ Microbiol. 1984;48(4):690–3.
Hu WJ, Chen XM, Meng HD, Meng ZH. Fermented corn flour poisoning in rural areas of China III. Isolation and identification of main toxin produced by causal microorganisms. Biomed Environ Sci. 1989;2(1):65–71.
van Veen AG. The bongkrek toxins. In: Mateles EI, Wogan GN, editors. Biochemistry of some foodborne microbial toxins. Cambridge: MIT Press; 1967. p. 43–50.
Zhao NX, Ma M, Zhang Y, Xu D. Comparative description of Pseudomonas cocovenenans NCIB9450 and strains isolated from cases of food poisoning caused by consumption of fermented corn flour in China. Int J Syst Bact. 1990;40(4):452–5.
Liu X. Microbiology risk assessment in China: current situation and challenges [PowerPoint slides]. 2002. http://foodrisk.org/default/assets/File/IRAC-event-2002-07-24-Liu.pdf. Accessed 14 Aug 2015.
Welling W, Cohen JA, Berends W. Disturbance of oxidative phosphorylation by an antibioticum produced by Pseudomonas cocovenenans. Biochem Pharmacol. 1960;3:122–35.
Brandt M. Introduction to Lipids. Rose-Hulman.edu. Rose-Hulman Institute of Technology. 2011. http://www.rose-hulman.edu/~brandt/Chem330/Lipid_properties.pdf. Accessed 27 Apr 2016.
Halestrap AP, Brenner C. The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem. 2003;10(6):1507–25.
Belzacq AS, Brenner C. The adenine nucleotide translocator: a new potential chemotherapeutic target. Curr Drug Targets. 2003;4(7):517–24.
Francais A, Leyva-Perez A, Extebarria-Jardi G, Pena J, Ley SV. Total synthesis of iso- and bongkrekic acids: natural antibiotics displaying potent antiapoptotic properties. Chemistry. 2011;17(1):329–43.
Henderson PJ, Lardy HA. Bongkrekic acid: an inhibitor of the adenine nucleotide translocase of mitochondria. J Biol Chem. 1970;245(6):1319–26.
Stubbs M. Inhibitors of the adenine nucleotide translocase. Pharmacol Ther. 1979;7(2):329–50.
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Anwar, M., Kasper, A., Steck, A.R. et al. Bongkrekic Acid—a Review of a Lesser-Known Mitochondrial Toxin. J. Med. Toxicol. 13, 173–179 (2017). https://doi.org/10.1007/s13181-016-0577-1
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DOI: https://doi.org/10.1007/s13181-016-0577-1