Abstract
In order that malaria be successfully contained, it is important that one has a clear understanding of the normal physiology and biochemistry of the parasite essential to its survival in its human host. Until very recently, the conventional approaches to antimalarial chemotherapy have consistently been plagued with the uncanny ability of the parasite to evolve resistance to drugs. The recently discovered plasmodial fatty acid biosynthetic pathway as well as its inhibition by triclosan that classifies it as belonging to type II, provide with a very crucial breakthrough to the crusade against malaria. How triclosan could tilt the balance in favor of the human hosts of the malarial parasite in a malarial condition is discussed.
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WHO Fact Sheet # 94: Revised October 1998
Surolia N, Satish PR, Surolia A: Paradigm shifts in malaria parasite biochemistry and anti-malarial chemotherapy. BioEssays 24: 192-196, 2002
Trigg PI, Kondrachine AV: The current global malaria situation. In: I.W. Sherman (ed). Malaria Parasite Biology, Pathogenesis, and Protection. ASM Press. Washington, D.C., 1998, pp 11-22
Milhous WK, Kyle DE: Introduction to the modes of action of and mechanisms of resistance to antimalarials. In: W. Sherman (ed). Malaria Parasite Biology, Pathogenesis, and Protection. ASM Press, Washington, D.C., 1998, pp 303-316
Surolia N, Padmanaban G: Chloroquine inhibits heme-dependent protein synthesis in Plasmodium falciparum. Proc Natl Acad Sci USA 88: 4786-4790, 1991
Padmanaban G, Rangarajan PN: Emerging targets for antimalarial drugs. Expert Opin Ther Targets 5: 423-441, 2001
Surolia N, Karthikeyan G, Padmanaban G: Involvement of cytochrome P-450 in conferring chloroquine resistance to the malarial parasite, Plasmodium falciparum. Biochem Biophys Res Commun 197: 562-569, 1993
Surolia N, Surolia A: Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nat Med 7: 167-173, 2001
Beeson JG, Winstanley PA, McFadden GI, Brown GV: New agents to combat malaria. Nature Med 7: 149-150, 2001
Suguna K, Surolia A, Surolia N: Structural basis for triclosan and NAD binding to enoyl-ACP reductase of Plasmodium falciparum. Biochem Biophys Res Commun 283: 224-228, 2001
Kapoor M, Jamal Dar M, Surolia A, Surolia N: Kinetic determinants of the interaction of enoyl-ACP reductase from Plasmodium falciparum with its substrates and inhibitors. Biochem Biophys Res Commun 289: 832-837, 2001
Surolia N, Padmanaban G: De novo biosynthesis of heme offers a new chemotherapeutic target in the human malarial parasite. Biochem Biophys Res Commun 187: 744-750, 1992
Surolia N, Misquith S: Cell surface receptor directed targeting of toxin to human malaria parasite, Plasmodium falciparum. FEBS Lett 396: 57-61, 1996
Surolia N: Receptor-mediated targeting of toxins to intraerythrocytic parasite Plasmodium falciparum. Adv Drug Deliv Rev 41: 163-170, 2000
Bachhawat K, Thomas CJ, Surolia N, Surolia A: Interaction of chloroquine and its analogues with heme: An isothermal titration calorimetric study. Biochem Biophys Res Commun 276: 1075-1079, 2000
Bhat GP, Surolia N: Triclosan and fatty acid synthesis in Plasmodium falciparum: New weapon for an old enemy. J Biosci 26: 1-3, 2001
Bhat GP, Surolia N: In vitro antimalarial activity of extracts of three plants used in the traditional medicine of India. Am J Trop Med Hyg 65: 304-308, 2001
Davis MS, Solbiati J, Cronan JE Jr: Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli. J Biol Chem 275: 28593-28598, 2000
Volpe JJ, Vagelos PR: Saturated fatty acid biosynthesis and its regulation. Annu Rev Biochem 42: 21-60, 1973
Rock CO, Cronan JE: Escherichia coli as a model for the regulation of dissociable (type II) fatty acid biosynthesis. Biochim Biophys Acta 1302: 1-16, 1996
Harwood JL: Recent advances in the biosynthesis of plant fatty acids. Biochim Biophys Acta 1301: 7-56, 1996
Schneider R, Brors B, Burger F, Camrath S, Weiss H: Two genes of the putative mitochondrial fatty acid synthase in the genome of Saccharomyces cerevisiae. Curr Genet 32: 384-388, 1997
Weeks G, Wakil SJ: Studies on the mechanism of fatty acid synthesis. J Biol Chem 243: 1180-1189, 1968
Matesanz F, Duran-Chica I, Alcina A: The cloning and expression of Pfacs1, a Plasmodium falciparum fatty acyl coenzyme A synthetase-1 targeted to the host erythrocyte cytoplasm. J Mol Biol 291: 59-70, 1999
Bergler H, Wallner P, Ebeling A, Leitinger B, Fuchsbichler S, Aschauer H, Kollenz G, Hogenauer G, Turnowsky F: Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli. J Biol Chem 269: 5493-5496, 1994
Heath RJ, Rock CO: Enoyl-acyl carrier protein reductase (FabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli. J Biol Chem 270: 26538-26542, 1995
McMurry LM, Oethinger M, Levy SB: Triclosan targets lipid synthesis. Nature 394: 531-532, 1998
Heath RJ, Rubin JR, Holland DR, Zhang E, Snow ME, Rock CO: Mechanism of triclosan inhibition of bacterial fatty acid synthesis. J Biol Chem 274: 11110-11114, 1999
Heath RJ, Yu YT, Shapiro MA, Olson E, Rock CO: Broad spectrum antimicrobial biocides target the FabI component of fatty acid synthesis. J Biol Chem 273: 30316-30320, 1998
Levy CW, Roujeinikova A, Sedelnikova S, Baker PJ, Stuitje AR, Slabas AR, Rice DW, Rafferty JB: Molecular basis of triclosan activity. Nature 398: 383-384, 1999
Fichera ME, Roos DS: A plastid organelle as a drug target in api-complexan parasites. Nature 390: 407-409, 1997
McFadden GI, Reith ME, Munholland J, Lang-Unnasch N: Plastid in human parasites. Nature 381: 482, 1996
McFadden GI, Waller RF: Plastids in parasites of humans. Bioessays 19: 1033-1040, 1997
Kohler S, Delwiche CF, Denny PW, Tilney LG, Webster P, Wilson RJ, Palmer JD, Roos DS: A plastid of probable green algal origin in Api-complexan parasites. Science 275: 1485-1489, 1997
Roos DS, Crawford MJ, Donald RG, Kissinger JC, Klimczak LJ, Striepen B: Origin, targeting, and function of the apicomplexan plastid. Curr Opin Microbiol 2: 426-432, 1999
McFadden GI, Roos DS: Apicomplexan plastids as drug targets. Trends Microbiol 7: 328-333, 1999
He CY, Shaw MK, Pletcher CH, Striepen B, Tilney LG, Roos DS: A plastid segregation defect in the protozoan parasite Toxoplasma gondii. EMBO J 20: 330-339, 2001
Wilson RJM, Denny PW, Preiser PR, Rangachari K, Roberts K, Roy A, Whyte A, Strath M, Moore DJ, Moore PW, Williamson DH: Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum. J Mol Biol 261: 155-172, 1996
Waller RF, Reed MB, Cowman AF. McFadden GI: Protein trafficking to the plastid of Plasmodium falciparum is via the secretory pathway. EMBO J 19: 1794-1802, 2000
Waller RF, Keeling PJ, Donald RG, Striepen B, Handman E, Lang-Unnasch N, Cowman AF, Besra GS, Roos DS, McFadden GI: Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proc Natl Acad Sci USA 95: 12352-12357, 1998
Heath RJ, White SW, Rock CO: Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics. Appl Microbiol Biotechnol 58: 695-703, 2002
Heath RJ, White SW, Rock CO: Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res 40: 467-497, 2001
Liu B, Wang Y, Fillgrove KL, Anderson VE: Triclosan inhibits enoyl-reductase of type I fatty acid synthase in vitro and is cytotoxic to MCF-7 and SKBr-3 breast cancer cells. Cancer Chemother Pharmacol 49: 187-193, 2002
Heath RJ, Li J, Roland GE, Rock CO: Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene. J Biol Chem 275: 4654-4659, 2000
Roujeinikova A, Levy CW, Rowsell S, Sedelnikova S, Baker PJ, Minshull CA, Mistry A, Colls JG, Camble R, Stuitje AR, Slabas AR, Rafferty JB, Pauptit RA, Viner R, Rice DW: Crystallographic analysis of triclosan bound to enoyl reductase. J Mol Biol 294: 527-535, 1999
Qiu X, Janson CA, Court RI, Smyth MG, Payne DJ, Abdel-Meguid SS: Molecular basis for triclosan activity involves a flipping loop in the active site. Protein Sci 8: 2529-2532, 1999
Perozzo R, Kuo M, Sidhu AS, Valiyaveettil JT, Bittman R, Jacobs WR Jr, Fidock DA, Sacchettini JC: Structural elucidation of the specificity of the antibacterial agent triclosan for malarial enoyl acyl carrier protein reductase. J Biol Chem 277: 13106-13114, 2002
Jones RD, Jampani HB, Newman JL, Lee AS: Triclosan: A review of effectiveness and safety in health care settings. Am J Infect Control 28: 184-196, 2000
Bhargava HN, Leonard PA: Triclosan: Applications and safety. Am J Infect Control 24: 209-218, 1996
Shapiro S, Giertsen E, Guggenheim B: An in vitro oral biofilm model for comparing the efficacy of antimicrobial mouthrinses. Caries Res 36: 93-100, 2002
Moran J, Addy M, Newcombe RG, Marlow I: A study to assess the plaque inhibitory action of a newly formulated triclosan toothpaste. J Clin Periodontol 28: 86-89, 2001
Saunders KA, Greenman J, McKenzie C: Ecological effects of triclosan and triclosan monophosphate on defined mixed cultures of oral species grown in continuous culture. J Antimicrob Chemother 45: 447-452, 2000
Meincke BE, Kranz RG, Lynch DL: Effect of Irgasan on bacterial growth and its adsorption into the cell wall. Microbios 28: 133-147, 1980
Loftsson T, Leeves N, Bjornsdottir B, Duffy L, Masson M: Effect of cyclodextrins and polymers on triclosan availability and substantivity in toothpastes in vivo. J Pharm Sci 88: 1254-1258, 1999
McClanahan SF, Bartizek RD: Effects of triclosan/copolymer dentifrice on dental plaque and gingivitis in a 3-month randomized controlled clinical trial: Influence of baseline gingivitis on observed efficacy. J Clin Dent 13: 167-178, 2002
Lang NP, Sander L, Barlow A, Brennan K, White DJ, Bacca L, Bartizek RD, McClanahan SF: Experimental gingivitis studies: Effects of triclosan and triclosan-containing dentifrices on dental plaque and gingivitis in three-week randomized controlled clinical trials. J Clin Dent 13: 158-66, 2002
Grossman E, Hou L, Bollmer BW, Court LK, McClary JM, Bennett S, Winston JL, McClanahan SF: Triclosan/pyrophosphate dentifrice: Dental plaque and gingivitis effects in a 6-month randomized controlled clinical study. J Clin Dent 13: 149-57, 2002
Montiel-Company JM, Almerich-Silla JM: Efficacy of two antiplaque and antigingivitis treatments in a group of young mentally retarded patients. Med Oral 7: 136-143, 2002
Cao C, Sha Y, Meng H, Kang J, Yeh CH, Chyon HY, Winston JL: A four-day study to evaluate the anti-plaque efficacy of an experimental triclosan-containing dentifrice. J Clin Dent 12: 87-91, 2001
Jones CL, Ritchie JA, Marsh PD, Van der Ouderaa F: The effect of long-term use of a dentifrice containing zinc citrate and a nonionic agent on the oral flora. J Dent Res 67: 46-50, 1988
Jannesson L, Renvert S, Kjellsdotter P, Gaffar A, Nabi N, Birkhed D: Effect of a triclosan-containing toothpaste supplemented with 10% xylitol on mutans streptococci in saliva and dental plaque. A 6-month clinical study. Caries Res 36: 36-39, 2002
Moran J, Addy M, Corry D, Newcombe RG, Haywood J: A study to assess the plaque inhibitory action of a new zinc citrate toothpaste formulation. J Clin Periodontol 28: 157-161, 2001
Sowinski JA, Battista GW, Petrone DM, Petrone ME, DeVizio W, Volpe AR: A clinical study to assess the anticalculus efficacy of a new dentifrice containing a special grade of silica (Colgate Total Plus Whitening Toothpaste): A clinical trial on adults. J Clin Dent 13: 65-68, 2002
Allen DR, Battista GW, Petrone DM, Petrone ME, Chaknis P, DeVizio W, Volpe AR. The clinical efficacy of Colgate Total Plus Whitening Toothpaste containing a special grade of silica and Colgate Total Fresh Stripe Toothpaste in the control of plaque and gingivitis: A six-month clinical study. J Clin Dent 13: 59-64, 2002
Volpe AR, Petrone ME, Prencipe M, DeVizio W: The efficacy of a dentifrice with caries, plaque, gingivitis, tooth whitening and oral malodor benefits. J Clin Dent 13: 55-58, 2002
Sowinski J, Ayad F, Petrone M, DeVizio W, Volpe A, Ellwood R, Davies R: Comparative investigations of the desensitising efficacy of a new dentifrice. J Clin Periodontol 28: 1032-1036, 2001
Pizzo G, Giuliana, D'Angelo MD: Effect of antimicrobial mouthrinses on the in vitro adhesion of Candida albicans to human buccal epithelial cells. Clin Oral Investig 5: 172-176, 2001
Drisko CH: Non-surgical periodontal therapy. Periodontol 2000 25: 77-88, 2001
Fraise AP: Susceptibility of antibiotic-resistant cocci to biocides. J Appl Microbiol 92Suppl: 158S-162S, 2002
Russell AD: Introduction of biocides into clinical practice and the impact on antibiotic-resistant bacteria. J Appl Microbiol 92(suppl): 121S-135S, 2002
Braid JJ, Wale MC: The antibacterial activity of triclosan-impregnated storage boxes against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus and Shewanella putrefaciens in conditions simulating domestic use. J Antimicrob Chemother 49: 87-94, 2002
Li Q, Lee JY, Castillo R, Hixon MS, Pujol C, Doppalapudi VR, Shepard HM, Wahl GM, Lobl TJ, Chan MF: NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced potency against beta-Lactamase-producing strains. Antimicrob Agents Chemother 46: 1262-1268, 2002
Bartzokas CA, Corkill JE, Makin T, Pinder DC: Assessment of the remanent antibacterial effect of a 2% triclosan-detergent preparation on the skin. J Hyg (Lond) 91: 521-528, 1983
Gautier G, Noguer M, Costa N, Canela J, Vinas M: Mouthrinses: A comparative microbiological study. Bull Group Int Rech Sci Stomatol Odontol 42: 23-29, 2000
Tung FF, Estafan D, Scherer W: The antimicrobial properties of a urea-based handwash lotion with triclosan. Gen Dent 49: 653-656, 2001
Loughlin MF, Jones MV, Lambert PA: Pseudomonas aeruginosa cells adapted to benzalkonium chloride show resistance to other membrane-active agents but not to clinically relevant antibiotics. J Antimicrob Chemother 49: 631-639, 2002
Vermeiren L, Devlieghere F, Debevere J: Effectiveness of some recent antimicrobial packaging concepts. Food Addit Contam 19(suppl): 163-171, 2002
Moss T, Howes D, Williams FM: Percutaneous penetration and dermal metabolism of triclosan (2,4, 4′-trichloro-2′-hydroxydiphenyl ether). Food Chem Toxicol 38: 361-370, 2000
Chedgzoy P, Winckle G, Heard CM: Triclosan: Release from transdermal adhesive formulations and in vitro permeation across human epidermal membranes. Int J Pharm 235: 229-236, 2002
Bagley DM, Lin YJ: Clinical evidence for the lack of triclosan accumulation from daily use in dentifrices. Am J Dent 13: 148-152, 2000
Lin YJ: Buccal absorption of triclosan following topical mouthrinse application. Am J Dent 13: 215-217, 2000
Piccoli A, Fiori J, Andrisano V, Orioli M: Determination of triclosan in personal health care products by liquid chromatography (HPLC). Farmaco 57: 369-372, 2002
Hovander L, Malmberg T, Athanasiadou M, Athanassiadis I, Rahm S, Bergman A, Wehler EK: Identification of hydroxylated PCB metabolites and other phenolic halogenated pollutants in human blood plasma. Arch Environ Contam Toxicol 42: 105-117, 2002
Hernandez-Richter TM, Wichmann MW, Schrodl W, Angele MK, Heinritzi K, Schildberg FW: The acute phase response following implantation of triclosan-bonded vascular prostheses. Clin Exp Med 1: 35-41, 2001
Hernandez-Richter T, Schardey HM, Lohlein F, Heiss MM, Redondo-Muller M, Hammer C, Schildberg FW: The prevention and treatment of vascular graft infection with a triclosan (Irgasan)-bonded Dacron graft: An experimental study in the pig. Eur J Vasc Endovasc Surg 20: 413-418, 2000
Zuckerbraun HL, Babich H, May R, Sinensky MC: Triclosan: Cytotoxicity, mode of action, and induction of apoptosis in human gingival cells in vitro. Eur J Oral Sci 106: 628-636, 1998
Orvos DR, Versteeg DJ, Inauen J, Capdevielle M, Rothenstein A, Cunningham V: Aquatic toxicity of triclosan. Environ Toxicol Chem 21: 1338-1349, 2002
Messager S, Goddard PA, Dettmar PW, Maillard JY: Determination of the antibacterial efficacy of several antiseptics tested on skin by an 'ex-vivo' test. J Med Microbiol 50: 284-292, 2001
Zaugg T, Hunziker T: Germall II and triclosan. Contact Dermatitis 17: 262, 1987
Slayden RA, Lee RE, Barry CE III: Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis. Mol Microbiol 38: 514-525, 2000
Parikh SL, Xiao G, Tonge PJ: Inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis, by triclosan and isoniazid. Biochemistry 39: 7645-7650, 2000
Hovander L, Malmberg T, Athanasiadou M, Athanassiadis I, Rahm S, Bergman A, Wehler EK: Identification of hydroxylated PCB metabolites and other phenolic halogenated pollutants in human blood plasma. Arch Environ Contam Toxicol 42: 105-117, 2002
Foran CM, Bennett ER, Benson WH: Developmental evaluation of a potential non-steroidal estrogen: Triclosan. Mar Environ Res 50: 153-156, 2000
Meade MJ, Waddell RL, Callahan TM: Soil bacteria Pseudomonas putida and Alcaligenes xylosoxidans subsp. denitrificans inactivate triclosan in liquid and solid substrates. FEMS Microbiol Lett 204: 45-48, 2001
Levy SB: Active efflux, a common mechanism for biocide and antibiotic resistance. J Appl Microbiol 92(suppl): 65S-71S, 2002
Schweizer HP: Triclosan: A widely used biocide and its link to antibiotics. FEMS Microbiol Lett 202: 1-7, 2001
Poole K: Mechanisms of bacterial biocide and antibiotic resistance. J Appl Microbiol 92(suppl): 55S-64S, 2002
Chuanchuen R, Beinlich K, Hoang TT, Becher A, Karkhoff-Schweizer RR, Schweizer HP: Cross-resistance between triclosan and antibiotics in Pseudomonas aeruginosa is mediated by multidrug efflux pumps: Exposure of a susceptible mutant strain to triclosan selects nfxB mutants overexpressing MexCD-OprJ. Antimicrob Agents Chemother 45: 428-432, 2001
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Ramachandra Rao, S.P., Surolia, A. & Surolia, N. Triclosan: A shot in the arm for antimalarial chemotherapy. Mol Cell Biochem 253, 55–63 (2003). https://doi.org/10.1023/A:1026049217966
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DOI: https://doi.org/10.1023/A:1026049217966