Genetic Diversity of the Flavohemoprotein Gene of Giardia lamblia: Evidence for High Allelic Heterozygosity and Copy Number Variation

References

• Lane S, Lloyd D. Current trends in research into the waterborne parasite Giardia. Crit Rev Microbiol. 2002;28(2):123–147. doi:10.1080/1040-84029104671312109771
   PubMed Web of Science ®Google Scholar
• Berkman DS, Lescano AG, Gilman RH, Lopez SL, Black MM. Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: a follow-up study. Lancet. 2002;359(9306):564–571. doi:10.1016/S0140-6736(02)07744-911867110
   PubMed Web of Science ®Google Scholar
• Rogawski ET, Platts-Mills JA, Seidman JC, et al. Early antibiotic exposure in low-resource settings is associated with increased weight in the first two years of life. J Pediatr Gastroenterol Nutr. 2017;65(3):350–356. doi:10.1097/MPG.000000000000164028604514
   PubMed Web of Science ®Google Scholar
• Craun GF, Calderon RL, Craun MF. Outbreaks associated with recreational water in the United States. Int J Environ Health Res. 2005;15(4):243–262. doi:10.1080/0960312050015571616175741
   PubMed Web of Science ®Google Scholar
• Farthing MJ. Giardiasis. Gastroenterol Clin North Am. 1996;25(3):493–515. doi:10.1016/S0889-8553(05)70260-08863037
   PubMed Web of Science ®Google Scholar
• Gardner TB, Hill DR. Treatment of giardiasis. Clin Microbiol Rev. 2001;14(1):114–128.11148005
   PubMed Web of Science ®Google Scholar
• Munoz Gutierrez J, Aldasoro E, Requena A, et al. Refractory giardiasis in Spanish travellers. Travel Med Infect Dis. 2013;11(2):126–129. doi:10.1016/j.tmaid.2012.10.00423218784
   PubMed Web of Science ®Google Scholar
• Requena-Mendez A, Goni P, Rubio E, et al. The use of quinacrine in nitroimidazole-resistant giardia duodenalis: an old drug for an emerging problem. J Infect Dis. 2017;215(6):946–953. doi:10.1093/infdis/jix06628453841
   PubMed Web of Science ®Google Scholar
• Nabarro LE, Lever RA, Armstrong M, Chiodini PL. Increased incidence of nitroimidazole-refractory giardiasis at the hospital for tropical diseases, London: 2008–2013. Clin Microbiol Infect. 2015;21(8):791–796. doi:10.1016/j.cmi.2015.04.01925975511
   PubMed Web of Science ®Google Scholar
• Dingsdag SA, Hunter N. Metronidazole: an update on metabolism, structure-cytotoxicity and resistance mechanisms. J Antimicrob Chemother. 2018;73(2):265–279. doi:10.1093/jac/dkx35129077920
   PubMed Web of Science ®Google Scholar
• Leitsch D. A review on metronidazole: an old warhorse in antimicrobial chemotherapy. Parasitology. 2017;1–12.
   Web of Science ®Google Scholar
• Church DL, Laishley EJ. Reduction of metronidazole by hydrogenase from clostridia. Anaerobe. 1995;1(2):81–92. doi:10.1006/anae.1995.100216887511
   PubMed Web of Science ®Google Scholar
• Mastronicola D, Falabella M, Forte E, Testa F, Sarti P, Giuffre A. Antioxidant defence systems in the protozoan pathogen Giardia intestinalis. Mol Biochem Parasitol. 2016;206(1–2):56–66. doi:10.1016/j.molbiopara.2015.12.00226672398
   PubMed Web of Science ®Google Scholar
• Ma’ayeh SY, Knorr L, Svard SG. Transcriptional profiling of Giardia intestinalis in response to oxidative stress. Int J Parasitol. 2015;45(14):925–938. doi:10.1016/j.ijpara.2015.07.00526341007
   PubMed Web of Science ®Google Scholar
• Mastronicola D, Testa F, Forte E, et al. Flavohemoglobin and nitric oxide detoxification in the human protozoan parasite Giardia intestinalis. Biochem Biophys Res Commun. 2010;399(4):654–658. doi:10.1016/j.bbrc.2010.07.13720691663
   PubMed Web of Science ®Google Scholar
• Gardner PR, Gardner AM, Martin LA, Salzman AL. Nitric oxide dioxygenase: an enzymic function for flavohemoglobin. Proc Natl Acad Sci U S A. 1998;95(18):10378–10383.9724711
   PubMed Web of Science ®Google Scholar
• Gardner PR. Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases. J Inorg Biochem. 2005;99(1):247–266. doi:10.1016/j.jinorgbio.2004.10.00315598505
   PubMed Web of Science ®Google Scholar
• Rafferty S, Luu B, March RE, Yee J. Giardia lamblia encodes a functional flavohemoglobin. Biochem Biophys Res Commun. 2010;399(3):347–351. doi:10.1016/j.bbrc.2010.07.07320655876
   PubMed Web of Science ®Google Scholar
• Ansell BR, McConville MJ, Baker L, et al. Divergent transcriptional responses to physiological and xenobiotic stress in giardia duodenalis. Antimicrob Agents Chemother. 2016;60(10):6034–6045. doi:10.1128/AAC.00977-1627458219
   PubMed Web of Science ®Google Scholar
• Müller J, Braga S, Heller M, Müller N. Resistance formation to nitro drugs in Giardia lamblia: no common markers identified by comparative proteomics. Int J Parasitol Drugs Drug Resist. 2019;9:112–119. doi:10.1016/j.ijpddr.2019.03.00230889439
   PubMed Web of Science ®Google Scholar
• Rasoloson D, Tomkova E, Cammack R, Kulda J, Tachezy J. Metronidazole-resistant strains of Trichomonas vaginalis display increased susceptibility to oxygen. Parasitology. 2001;123(\(Pt1)):45–56. doi:10.1017/S003118200100802211467782
   PubMed Web of Science ®Google Scholar
• Ansell BR, McConville MJ, Ma’ayeh SY, et al. Drug resistance in Giardia duodenalis. Biotechnol Adv. 2015;33(6 Pt 1):888–901. doi:10.1016/j.biotechadv.2015.04.00925922317
   PubMed Web of Science ®Google Scholar
• Forrester MT, Foster MW. Protection from nitrosative stress: a central role for microbial flavohemoglobin. Free Radic Biol Med. 2012;52(9):1620–1633. doi:10.1016/j.freeradbiomed.2012.01.02822343413
   PubMed Web of Science ®Google Scholar
• Helmick RA, Fletcher AE, Gardner AM, et al. Imidazole antibiotics inhibit the nitric oxide dioxygenase function of microbial flavohemoglobin. Antimicrob Agents Chemother. 2005;49(5):1837–1843. doi:10.1128/AAC.49.5.1837-1843.200515855504
   PubMed Web of Science ®Google Scholar
• Yu LZ, Birky CW Jr, Adam RD. The two nuclei of Giardia each have complete copies of the genome and are partitioned equationally at cytokinesis. Eukaryotic Cell. 2002;1(2):191–199. doi:10.1128/EC.1.2.191-199.200212455954
   PubMedGoogle Scholar
• Bernander R, Palm JE, Svard SG. Genome ploidy in different stages of the Giardia lamblia life cycle. Cell Microbiol. 2001;3(1):55–62. doi:10.1046/j.1462-5822.2001.00094.x11207620
   PubMed Web of Science ®Google Scholar
• Kabnick KS, Peattie DA. In situ analyses reveal that the two nuclei of Giardia lamblia are equivalent. J Cell Sci. 1990;95(Pt 3):353–360.2384520
   PubMed Web of Science ®Google Scholar
• Tumova P, Uzlikova M, Jurczyk T, Nohynkova E. Constitutive aneuploidy and genomic instability in the single-celled eukaryote Giardia intestinalis. MicrobiologyOpen. 2016;5(4):560–574. doi:10.1002/mbo3.35127004936
   PubMed Web of Science ®Google Scholar
• Ankarklev J, Svard SG, Lebbad M. Allelic sequence heterozygosity in single Giardia parasites. BMC Microbiol. 2012;12:65. doi:10.1186/1471-2180-12-6522554281
   PubMed Web of Science ®Google Scholar
• Franzen O, Jerlstrom-Hultqvist J, Castro E, et al. Draft genome sequencing of giardia intestinalis assemblage B isolate GS: is human giardiasis caused by two different species? PLoS Pathog. 2009;5(8):e1000560.19696920
   PubMed Web of Science ®Google Scholar
• Choy SH, Mahdy MA, Al-Mekhlafi HM, Low VL, Surin J. Population expansion and gene flow in Giardia duodenalis as revealed by triosephosphate isomerase gene. Parasit Vectors. 2015;8:454. doi:10.1186/s13071-015-1084-y26373536
   PubMed Web of Science ®Google Scholar
• Caccio SM, Ryan U. Molecular epidemiology of giardiasis. Mol Biochem Parasitol. 2008;160(2):75–80. doi:10.1016/j.molbiopara.2008.04.00618501440
   PubMed Web of Science ®Google Scholar
• Hussein AI, Yamaguchi T, Nakamoto K, Iseki M, Tokoro M. Multiple-subgenotype infections of Giardia intestinalis detected in Palestinian clinical cases using a subcloning approach. Parasitol Int. 2009;58(3):258–262.19361570
   PubMed Web of Science ®Google Scholar
• Lalle M, Pozio E, Capelli G, Bruschi F, Crotti D, Cacciò SM. Genetic heterogeneity at the beta-giardin locus among human and animal isolates of Giardiaduodenalis and identification of potentially zoonotic subgenotypes. Int J Parasitol. 2005;35(2):207–213. doi:10.1016/j.ijpara.2004.10.02215710441
   PubMed Web of Science ®Google Scholar
• Gabin-Garcia LB, Bartolome C, Abal-Fabeiro JL, Mendez S, Llovo J, Maside X. Strong genetic structure revealed by multilocus patterns of variation in Giardia duodenalis isolates of patients from Galicia (NW-Iberian Peninsula). Infect Genet Evol. 2017;48:131–141. doi:10.1016/j.meegid.2016.12.01427993728
   PubMed Web of Science ®Google Scholar
• Kosuwin R, Putaporntip C, Pattanawong U, Jongwutiwes S. Clonal diversity in Giardia duodenalis isolates from Thailand: evidences for intragenic recombination and purifying selection at the beta giardin locus. Gene. 2010;449(1–2):1–8. doi:10.1016/j.gene.2009.09.01019796671
   PubMed Web of Science ®Google Scholar
• Siripattanapipong S, Leelayoova S, Mungthin M, et al. Clonal diversity of the glutamate dehydrogenase gene in Giardia duodenalis from Thai isolates: evidence of genetic exchange or mixed infections? BMC Microbiol. 2011;11:206. doi:10.1186/1471-2180-11-20621933419
   PubMed Web of Science ®Google Scholar
• Lasek-Nesselquist E, Welch DM, Thompson RC, Steuart RF, Sogin ML. Genetic exchange within and between assemblages of Giardia duodenalis. J Eukaryot Microbiol. 2009;56(6):504–518. doi:10.1111/j.1550-7408.2009.00443.x19883439
   PubMed Web of Science ®Google Scholar
• Mizuno T, Matey EJ, Bi X, Songok EM, Ichimura H, Tokoro M. Extremely diversified haplotypes observed among assemblage B population of Giardia intestinalis in Kenya. Parasitol Int. 2020;75:102038. doi:10.1016/j.parint.2019.10203831837398
   PubMed Web of Science ®Google Scholar
• Lecova L, Tumova P, Nohynkova E. Clone-based haplotyping of Giardia intestinalis assemblage B human isolates. Parasitol Res. 2019;118(1):355–361. doi:10.1007/s00436-018-6161-730488254
   PubMed Web of Science ®Google Scholar
• Aguiar JM, Silva SO, Santos VA, et al. Evidence of heterozygosity and recombinant alleles in single cysts of Giardia duodenalis. Revista Brasileira De Parasitologia Veterinaria. 2016;25(2):187–195. doi:10.1590/S1984-2961201603127334819
   PubMed Web of Science ®Google Scholar
• Saghaug CS, Klotz C, Kallio JP, et al. Genetic variation in metronidazole metabolism and oxidative stress pathways in clinical Giardia lamblia assemblage A and B isolates. Infect Drug Resist. 2019;12:1221–1235. doi:10.2147/IDR.S17799731190910
   PubMed Web of Science ®Google Scholar
• Keister DB. Axenic culture of Giardia lamblia in TYI-S-33 medium supplemented with bile. Trans R Soc Trop Med Hyg. 1983;77(4):487–488. doi:10.1016/0035-9203(83)90120-76636276
   PubMed Web of Science ®Google Scholar
• Aurrecoechea C, Brestelli J, Brunk BP, et al. GiardiaDB and TrichDB: integrated genomic resources for the eukaryotic protist pathogens Giardia lamblia and Trichomonas vaginalis. Nucleic Acids Res. 2009;37(Databaseissue):D526–530. doi:10.1093/nar/gkn63118824479
   PubMed Web of Science ®Google Scholar
• Inoue H, Nojima H, Okayama H. High efficiency transformation of Escherichia coli with plasmids. Gene. 1990;96(1):23–28. doi:10.1016/0378-1119(90)90336-P2265755
   PubMed Web of Science ®Google Scholar
• Rozas J, Ferrer-Mata A, Sanchez-DelBarrio JC, et al. DnaSP 6: DNA sequence polymorphism analysis of large data sets. Mol Biol Evol. 2017;34(12):3299–3302. doi:10.1093/molbev/msx24829029172
   PubMed Web of Science ®Google Scholar
• Rozas J, Sanchez-DelBarrio JC, Messeguer X, Rozas R. DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics. 2003;19(18):2496–2497. doi:10.1093/bioinformatics/btg35914668244
   PubMed Web of Science ®Google Scholar
• Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015;10(6):845–858. doi:10.1038/nprot.2015.05325950237
   PubMed Web of Science ®Google Scholar
• Ilari A, Bonamore A, Farina A, Johnson KA, Boffi A. The X-ray structure of ferric Escherichia coli flavohemoglobin reveals an unexpected geometry of the distal heme pocket. J Biol Chem. 2002;277(26):23725–23732. doi:10.1074/jbc.M20222820011964402
   PubMed Web of Science ®Google Scholar
• Grantham R. Amino acid difference formula to help explain protein evolution. Science. 1974;185(4154):862–864. doi:10.1126/science.185.4154.8624843792
   PubMed Web of Science ®Google Scholar
• Ermler U, Siddiqui RA, Cramm R, Friedrich B. Crystal structure of the flavohemoglobin from Alcaligenes eutrophus at 1.75 A resolution. EMBO J. 1995;14(24):6067–6077. doi:10.1002/j.1460-2075.1995.tb00297.x8557026
   PubMed Web of Science ®Google Scholar
• El Hammi E, Warkentin E, Demmer U, Marzouki NM, Ermler U, Baciou L. Active site analysis of yeast flavohemoglobin based on its structure with a small ligand or econazole. FEBS J. 2012;279(24):4565–4575. doi:10.1111/febs.1204323095020
   PubMed Web of Science ®Google Scholar
• Potapov V, Ong JL. Examining sources of error in PCR by single-molecule sequencing. PLoS One. 2017;12(1):e0169774. doi:10.1371/journal.pone.016977428060945
   PubMed Web of Science ®Google Scholar
• Teodorovic S, Braverman JM, Elmendorf HG. Unusually low levels of genetic variation among Giardia lamblia isolates. Eukaryotic Cell. 2007;6(8):1421–1430. doi:10.1128/EC.00138-0717557879
   PubMedGoogle Scholar
• Adam RD, Dahlstrom EW, Martens CA, et al. Genome sequencing of Giardia lamblia genotypes A2 and B isolates (DH and GS) and comparative analysis with the genomes of genotypes A1 and E (WB and Pig). Genome Biol Evol. 2013;5(12):2498–2511. doi:10.1093/gbe/evt19724307482
   PubMed Web of Science ®Google Scholar
• Morrison HG, McArthur AG, Gillin FD, et al. Genomic minimalism in the early diverging intestinal parasite Giardia lamblia. Science. 2007;317(5846):1921–1926. doi:10.1126/science.114383717901334
   PubMed Web of Science ®Google Scholar
• Benere E, Geurden T, Robertson L, Van Assche T, Cos P, Maes L. Infectivity of Giardia duodenalis Assemblages A and E for the gerbil and axenisation of duodenal trophozoites. Parasitol Int. 2010;59(4):634–637. doi:10.1016/j.parint.2010.08.00120696269
   PubMed Web of Science ®Google Scholar
• Binz N, Thompson RC, Lymbery AJ, Hobbs RP. Comparative studies on the growth dynamics of two genetically distinct isolates of Giardia duodenalis in vitro. Int J Parasitol. 1992;22(2):195–202. doi:10.1016/0020-7519(92)90101-P1587683
   PubMed Web of Science ®Google Scholar
• Caccio SM, Sprong H. Giardia duodenalis: genetic recombination and its implications for taxonomy and molecular epidemiology. Exp Parasitol. 2010;124(1):107–112. doi:10.1016/j.exppara.2009.02.00719236865
   PubMed Web of Science ®Google Scholar
• Bussotti G, Gouzelou E, Côrtes Boité M, et al. Leishmania genome dynamics during environmental adaptation reveal strain-specific differences in gene copy number variation, karyotype instability, and telomeric amplification. mBio. 2018;9:6. doi:10.1128/mBio.01399-18
   Web of Science ®Google Scholar
• Imamura H, Downing T, Van den Broeck F, et al. Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent. Elife. 2016;5.
   Web of Science ®Google Scholar
• Domagalska MA, Imamura H, Sanders M, et al. Genomes of Leishmania parasites directly sequenced from patients with visceral leishmaniasis in the Indian subcontinent. PLoS Negl Trop Dis. 2019;13(12):e0007900. doi:10.1371/journal.pntd.000790031830038
   PubMed Web of Science ®Google Scholar
• Argüello-García R, Leitsch D, Skinner-Adams T, Ortega-Pierres MG. Drug resistance in giardia: mechanisms and alternative treatments for giardiasis. Adv Parasitol. 2020;107:201–282.32122530
   PubMed Web of Science ®Google Scholar
• Weetman D, Djogbenou LS, Lucas E. Copy number variation (CNV) and insecticide resistance in mosquitoes: evolving knowledge or an evolving problem? Current Opinion Insect Sci. 2018;27:82–88. doi:10.1016/j.cois.2018.04.005
   Web of Science ®Google Scholar
• Wertheimer NB, Stone N, Berman J. Ploidy dynamics and evolvability in fungi. Philos Trans R Soc Lond B Biol Sci. 2016;371:1709.
   Web of Science ®Google Scholar
• Müller J, Hemphill A, Müller N. Physiological aspects of nitro drug resistance in Giardia lamblia. Int J Parasitol Drugs Drug Resist. 2018;8(2):271–277. doi:10.1016/j.ijpddr.2018.04.00829738984
   PubMed Web of Science ®Google Scholar
• Ansell BR, Baker L, Emery SJ, et al. Transcriptomics indicates active and passive metronidazole resistance mechanisms in three seminal giardia lines. Front Microbiol. 2017;8:398. doi:10.3389/fmicb.2017.0039828367140
   PubMed Web of Science ®Google Scholar
• Bradic M, Warring SD, Tooley GE, et al. Genetic indicators of drug resistance in the highly repetitive genome of trichomonas vaginalis. Genome Biol Evol. 2017;9(6):1658–1672. doi:10.1093/gbe/evx11028633446
   PubMed Web of Science ®Google Scholar