Knockdown resistance mutations are common and widely distributed in Xenopsylla cheopis fleas that transmit plague in Madagascar.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
27
10
2022
accepted:
22
05
2023
medline:
24
8
2023
pubmed:
22
8
2023
entrez:
22
8
2023
Statut:
epublish
Résumé
Plague, caused by the bacterium Yersinia pestis, remains an important disease in Madagascar, where the oriental rat flea, Xenopsylla cheopis, is a primary vector. To control fleas, synthetic pyrethroids (SPs) have been used for >20 years, resulting in resistance in many X. cheopis populations. The most common mechanisms of SP resistance are target site mutations in the voltage-gated sodium channel (VGSC) gene. We obtained 25 collections of X. cheopis from 22 locations across Madagascar and performed phenotypic tests to determine resistance to deltamethrin, permethrin, and/or dichlorodiphenyltrichloroethane (DDT). Most populations were resistant to all these insecticides. We sequenced a 535 bp segment of the VGSC gene and identified two different mutations encoding distinct substitutions at amino acid position 1014, which is associated with knockdown resistance (kdr) to SPs in insects. Kdr mutation L1014F occurred in all 25 collections; a rarer mutation, L1014H, was found in 12 collections. There was a significant positive relationship between the frequency of kdr alleles and the proportion of individuals surviving exposure to deltamethrin. Phylogenetic comparisons of 12 VGSC alleles in Madagascar suggested resistant alleles arose from susceptible lineages at least three times. Because genotype can reasonably predict resistance phenotype, we developed a TaqMan PCR assay for the rapid detection of kdr resistance alleles. Our study provides new insights into VGSC mutations in Malagasy populations of X. cheopis and is the first to report a positive correlation between VGSC genotypes and SP resistance phenotypes in fleas. Widespread occurrence of these two SP resistance mutations in X. cheopis populations in Madagascar reduces the viability of these insecticides for flea control. However, the TaqMan assay described here facilitates rapid detection of kdr mutations to inform when use of these insecticides is still warranted to reduce transmission of plague.
Sections du résumé
BACKGROUND
Plague, caused by the bacterium Yersinia pestis, remains an important disease in Madagascar, where the oriental rat flea, Xenopsylla cheopis, is a primary vector. To control fleas, synthetic pyrethroids (SPs) have been used for >20 years, resulting in resistance in many X. cheopis populations. The most common mechanisms of SP resistance are target site mutations in the voltage-gated sodium channel (VGSC) gene.
METHODOLOGY/PRINCIPAL FINDINGS
We obtained 25 collections of X. cheopis from 22 locations across Madagascar and performed phenotypic tests to determine resistance to deltamethrin, permethrin, and/or dichlorodiphenyltrichloroethane (DDT). Most populations were resistant to all these insecticides. We sequenced a 535 bp segment of the VGSC gene and identified two different mutations encoding distinct substitutions at amino acid position 1014, which is associated with knockdown resistance (kdr) to SPs in insects. Kdr mutation L1014F occurred in all 25 collections; a rarer mutation, L1014H, was found in 12 collections. There was a significant positive relationship between the frequency of kdr alleles and the proportion of individuals surviving exposure to deltamethrin. Phylogenetic comparisons of 12 VGSC alleles in Madagascar suggested resistant alleles arose from susceptible lineages at least three times. Because genotype can reasonably predict resistance phenotype, we developed a TaqMan PCR assay for the rapid detection of kdr resistance alleles.
CONCLUSIONS/SIGNIFICANCE
Our study provides new insights into VGSC mutations in Malagasy populations of X. cheopis and is the first to report a positive correlation between VGSC genotypes and SP resistance phenotypes in fleas. Widespread occurrence of these two SP resistance mutations in X. cheopis populations in Madagascar reduces the viability of these insecticides for flea control. However, the TaqMan assay described here facilitates rapid detection of kdr mutations to inform when use of these insecticides is still warranted to reduce transmission of plague.
Identifiants
pubmed: 37607174
doi: 10.1371/journal.pntd.0011401
pii: PNTD-D-22-01361
pmc: PMC10443838
doi:
Substances chimiques
decamethrin
2JTS8R821G
Insecticides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0011401Informations de copyright
Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Mol Biol Evol. 2018 Jun 1;35(6):1547-1549
pubmed: 29722887
J Med Entomol. 2008 Mar;45(2):260-6
pubmed: 18402142
Parasit Vectors. 2014 Oct 01;7:456
pubmed: 25266983
PLoS One. 2014 Nov 04;9(11):e111998
pubmed: 25369291
Trop Med Int Health. 2008 Dec;13(12):1479-87
pubmed: 18983277
J Am Mosq Control Assoc. 1998 Jun;14(2):159-64
pubmed: 9673916
Med Trop (Mars). 1966;26:Suppl 26:79+
pubmed: 6011187
PLoS One. 2013 Apr 08;8(4):e60878
pubmed: 23593337
J Wildl Dis. 2021 Apr 1;57(2):434-438
pubmed: 33631008
Nat Rev Genet. 2011 Sep 16;12(10):703-14
pubmed: 21921926
Emerg Infect Dis. 2006 Mar;12(3):460-7
pubmed: 16704785
PLoS Negl Trop Dis. 2020 Aug 27;14(8):e0008251
pubmed: 32853251
Infect Dis Poverty. 2017 Nov 7;6(1):141
pubmed: 29110719
Pest Manag Sci. 2008 Nov;64(11):1126-30
pubmed: 18561309
Biochem J. 2006 Jun 1;396(2):255-63
pubmed: 16475981
Annu Rev Entomol. 2005;50:505-28
pubmed: 15471529
J Hyg (Lond). 1958 Dec;56(4):455-65
pubmed: 13611242
PLoS One. 2010 Jul 21;5(7):e11681
pubmed: 20657783
BMC Infect Dis. 2014 Aug 15;14:441
pubmed: 25127882
J Econ Entomol. 2018 Dec 14;111(6):2992-2995
pubmed: 30277509
Parasit Vectors. 2015 Jul 07;8:357
pubmed: 26148484
mBio. 2013 Feb 12;4(1):e00623-12
pubmed: 23404402
Lancet. 2016 Apr 23;387(10029):1785-8
pubmed: 26880124
World Health Organ Tech Rep Ser. 1970;443:1-279
pubmed: 4986494
PLoS Negl Trop Dis. 2013 Nov 07;7(11):e2382
pubmed: 24244760
Arch Toxicol. 2012 Feb;86(2):165-81
pubmed: 21710279
Nature. 1961 Aug 26;191:884-5
pubmed: 13699559
Infect Dis Poverty. 2018 Sep 4;7(1):86
pubmed: 30176907
J Med Entomol. 2001 Mar;38(2):193-6
pubmed: 11296822
JAMA. 2000 May 3;283(17):2281-90
pubmed: 10807389
Insect Biochem Mol Biol. 2014 Jul;50:1-17
pubmed: 24704279
PLoS Negl Trop Dis. 2016 Feb 04;10(2):e0004414
pubmed: 26844772
Insect Biochem Mol Biol. 2004 Dec;34(12):1305-13
pubmed: 15544944
Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):5938-5943
pubmed: 29784773
Insect Mol Biol. 2016 Apr;25(2):126-37
pubmed: 26691197
J Gen Physiol. 2000 Mar;115(3):305-18
pubmed: 10694259
Bull World Health Organ. 1969;40(5):731-44
pubmed: 5307234
Acta Trop. 2019 Mar;191:146-154
pubmed: 30552882
Insect Biochem Mol Biol. 1998 Dec;28(12):1031-7
pubmed: 9887519
Clin Microbiol Rev. 1997 Jan;10(1):35-66
pubmed: 8993858
Pest Manag Sci. 2008 Jun;64(6):610-6
pubmed: 18383430
Lancet Infect Dis. 2019 May;19(5):537-545
pubmed: 30930106
Vet Parasitol. 2012 Apr 30;185(2-4):274-8
pubmed: 22004914
Pestic Biochem Physiol. 2018 Apr;146:97-105
pubmed: 29626998
PLoS One. 2012;7(8):e42857
pubmed: 22880123
Evolution. 1985 Jul;39(4):783-791
pubmed: 28561359
Malar J. 2007 May 02;6:52
pubmed: 17474975
Parasit Vectors. 2017 Jul 20;10(1):347
pubmed: 28728588
Nat Genet. 2010 Dec;42(12):1140-3
pubmed: 21037571
Pest Manag Sci. 2012 Nov;68(11):1431-7
pubmed: 22945853
Mol Ecol. 2014 Aug;23(16):4153-67
pubmed: 24975563
Malar J. 2004 Jul 08;3:22
pubmed: 15242513
Parasit Vectors. 2019 Nov 6;12(1):526
pubmed: 31694689
Arch Inst Pasteur Madagascar. 2002;68(1-2):51-4
pubmed: 12643093
Insect Biochem Mol Biol. 2011 Sep;41(9):723-32
pubmed: 21640822
PLoS Negl Trop Dis. 2019 Aug 6;13(8):e0007604
pubmed: 31386661
Pest Manag Sci. 2010 Feb;66(2):137-41
pubmed: 19757499