Vectorial capacity and TEP1 genotypes of Anopheles gambiae sensu lato mosquitoes on the Kenyan coast.
Allele
Anopheles merus
Kenya
Thioester-containing protein 1
Journal
Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774
Informations de publication
Date de publication:
01 Dec 2022
01 Dec 2022
Historique:
received:
16
05
2022
accepted:
15
09
2022
entrez:
2
12
2022
pubmed:
3
12
2022
medline:
6
12
2022
Statut:
epublish
Résumé
Malaria remains one of the most important infectious diseases in sub-Saharan Africa, responsible for approximately 228 million cases and 602,000 deaths in 2020. In this region, malaria transmission is driven mainly by mosquitoes of the Anopheles gambiae and, more recently, Anopheles funestus complex. The gains made in malaria control are threatened by insecticide resistance and behavioural plasticity among these vectors. This, therefore, calls for the development of alternative approaches such as malaria transmission-blocking vaccines or gene drive systems. The thioester-containing protein 1 (TEP1) gene, which mediates the killing of Plasmodium falciparum in the mosquito midgut, has recently been identified as a promising target for gene drive systems. Here we investigated the frequency and distribution of TEP1 alleles in wild-caught malaria vectors on the Kenyan coast. Mosquitoes were collected using CDC light traps both indoors and outdoors from 20 houses in Garithe village, along the Kenyan coast. The mosquitoes were dissected, and the different parts were used to determine their species, blood meal source, and sporozoite status. The data were analysed and visualised using the R (v 4.0.1) and STATA (v 17.0). A total of 18,802 mosquitoes were collected, consisting of 77.8% (n = 14,631) Culex spp., 21.4% (n = 4026) An. gambiae sensu lato, 0.4% (n = 67) An. funestus, and 0.4% (n = 78) other Anopheles (An. coustani, An. pharoensis, and An. pretoriensis). Mosquitoes collected were predominantly exophilic, with the outdoor catches being higher across all the species: Culex spp. 93% (IRR = 11.6, 95% Cl [5.9-22.9] P < 0.001), An. gambiae s.l. 92% (IRR = 7.2, 95% Cl [3.6-14.5]; P < 0.001), An. funestus 91% (IRR = 10.3, 95% Cl [3.3-32.3]; P < 0.001). A subset of randomly selected An. gambiae s.l. (n = 518) was identified by polymerase chain reaction (PCR), among which 77.2% were An. merus, 22% were An. arabiensis, and the rest were not identified. We were also keen on identifying and describing the TEP1 genotypes of these mosquitoes, especially the *R3/R3 allele that was identified recently in the study area. We identified the following genotypes among An. merus: *R2/R2, *R3/R3, *R3/S2, *S1/S1, and *S2/S2. Among An. arabiensis, we identified *R2/R2, *S1/S1, and *S2/S2. Tests on haplotype diversity showed that the most diverse allele was TEP1*S1, followed by TEP1*R2. Tajima's D values were positive for TEP1*S1, indicating that there is a balancing selection, negative for TEP1*R2, indicating there is a recent selective sweep, and as for TEP1*R3, there was no evidence of selection. Phylogenetic analysis showed two distinct clades: refractory and susceptible alleles. We find that the malaria vectors An. gambiae s.l. and An. funestus are predominantly exophilic. TEP1 genotyping for An. merus revealed five allelic combinations, namely *R2/R2, *R3/R3, *R3/S2, *S1/S1 and *S2/S2, while in An. arabiensis we only identified three allelic combinations: *R2/R2, *S1/S1, and *S2/S2. The TEP1*R3 allele was restricted to only An. merus among these sympatric mosquito species, and we find that there is no evidence of recombination or selection in this allele.
Sections du résumé
BACKGROUND
BACKGROUND
Malaria remains one of the most important infectious diseases in sub-Saharan Africa, responsible for approximately 228 million cases and 602,000 deaths in 2020. In this region, malaria transmission is driven mainly by mosquitoes of the Anopheles gambiae and, more recently, Anopheles funestus complex. The gains made in malaria control are threatened by insecticide resistance and behavioural plasticity among these vectors. This, therefore, calls for the development of alternative approaches such as malaria transmission-blocking vaccines or gene drive systems. The thioester-containing protein 1 (TEP1) gene, which mediates the killing of Plasmodium falciparum in the mosquito midgut, has recently been identified as a promising target for gene drive systems. Here we investigated the frequency and distribution of TEP1 alleles in wild-caught malaria vectors on the Kenyan coast.
METHODS
METHODS
Mosquitoes were collected using CDC light traps both indoors and outdoors from 20 houses in Garithe village, along the Kenyan coast. The mosquitoes were dissected, and the different parts were used to determine their species, blood meal source, and sporozoite status. The data were analysed and visualised using the R (v 4.0.1) and STATA (v 17.0).
RESULTS
RESULTS
A total of 18,802 mosquitoes were collected, consisting of 77.8% (n = 14,631) Culex spp., 21.4% (n = 4026) An. gambiae sensu lato, 0.4% (n = 67) An. funestus, and 0.4% (n = 78) other Anopheles (An. coustani, An. pharoensis, and An. pretoriensis). Mosquitoes collected were predominantly exophilic, with the outdoor catches being higher across all the species: Culex spp. 93% (IRR = 11.6, 95% Cl [5.9-22.9] P < 0.001), An. gambiae s.l. 92% (IRR = 7.2, 95% Cl [3.6-14.5]; P < 0.001), An. funestus 91% (IRR = 10.3, 95% Cl [3.3-32.3]; P < 0.001). A subset of randomly selected An. gambiae s.l. (n = 518) was identified by polymerase chain reaction (PCR), among which 77.2% were An. merus, 22% were An. arabiensis, and the rest were not identified. We were also keen on identifying and describing the TEP1 genotypes of these mosquitoes, especially the *R3/R3 allele that was identified recently in the study area. We identified the following genotypes among An. merus: *R2/R2, *R3/R3, *R3/S2, *S1/S1, and *S2/S2. Among An. arabiensis, we identified *R2/R2, *S1/S1, and *S2/S2. Tests on haplotype diversity showed that the most diverse allele was TEP1*S1, followed by TEP1*R2. Tajima's D values were positive for TEP1*S1, indicating that there is a balancing selection, negative for TEP1*R2, indicating there is a recent selective sweep, and as for TEP1*R3, there was no evidence of selection. Phylogenetic analysis showed two distinct clades: refractory and susceptible alleles.
CONCLUSIONS
CONCLUSIONS
We find that the malaria vectors An. gambiae s.l. and An. funestus are predominantly exophilic. TEP1 genotyping for An. merus revealed five allelic combinations, namely *R2/R2, *R3/R3, *R3/S2, *S1/S1 and *S2/S2, while in An. arabiensis we only identified three allelic combinations: *R2/R2, *S1/S1, and *S2/S2. The TEP1*R3 allele was restricted to only An. merus among these sympatric mosquito species, and we find that there is no evidence of recombination or selection in this allele.
Identifiants
pubmed: 36457004
doi: 10.1186/s13071-022-05491-5
pii: 10.1186/s13071-022-05491-5
pmc: PMC9713959
doi:
Substances chimiques
Malaria Vaccines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
448Subventions
Organisme : The Royal Society
ID : FLR_R1_190497
Informations de copyright
© 2022. The Author(s).
Références
J Med Entomol. 1991 Nov;28(6):805-8
pubmed: 1770515
Bioinformatics. 2009 Jun 1;25(11):1451-2
pubmed: 19346325
Cell. 2004 Mar 5;116(5):661-70
pubmed: 15006349
PLoS One. 2017 May 18;12(5):e0177807
pubmed: 28542335
Am J Trop Med Hyg. 2002 Jun;66(6):804-11
pubmed: 12224596
Parasit Vectors. 2021 Jan 28;14(1):84
pubmed: 33509262
J Infect Dis. 2021 Apr 27;223(12 Suppl 2):S155-S170
pubmed: 33906217
Parasit Vectors. 2013 Feb 14;6:37
pubmed: 23410133
J Vis Exp. 2013 Jan 09;(71):
pubmed: 23328684
Parasit Vectors. 2013 Apr 20;6:114
pubmed: 23601146
PLoS One. 2013 Aug 15;8(8):e74511
pubmed: 23977401
Am J Trop Med Hyg. 2003 Jun;68(6):734-42
pubmed: 12887036
Genetics. 1993 Mar;133(3):693-709
pubmed: 8454210
BMC Evol Biol. 2008 Oct 07;8:274
pubmed: 18840262
Mol Biochem Parasitol. 2001 Dec;118(2):247-51
pubmed: 11738714
Parasit Vectors. 2010 Dec 03;3:117
pubmed: 21129198
Science. 2009 Oct 2;326(5949):147-50
pubmed: 19797663
PLoS Biol. 2015 Sep 22;13(9):e1002255
pubmed: 26394016
J Am Mosq Control Assoc. 2003 Dec;19(4):371-5
pubmed: 14710739
Malar J. 2013 Jan 08;12:13
pubmed: 23297732
Clin Microbiol Infect. 2013 Oct;19(10):902-7
pubmed: 23910459
Mem Inst Oswaldo Cruz. 2014 Aug;109(5):644-61
pubmed: 25185005
Malar J. 2007 Jul 30;6:100
pubmed: 17663787
Sci Rep. 2021 Jun 29;11(1):13457
pubmed: 34188090
Nat Microbiol. 2019 Jun;4(6):941-947
pubmed: 30911126
Mol Biol Evol. 2020 May 1;37(5):1530-1534
pubmed: 32011700
Malar J. 2011 Jul 07;10:184
pubmed: 21736750
Am J Trop Med Hyg. 1993 Oct;49(4):520-9
pubmed: 8214283
J Med Entomol. 1988 Jan;25(1):9-16
pubmed: 3357176
Malar J. 2011 Apr 09;10:80
pubmed: 21477321
Am J Trop Med Hyg. 2010 Oct;83(4):848-53
pubmed: 20889878
Parasit Vectors. 2021 Apr 20;14(1):207
pubmed: 33879244
Genetics. 1989 Nov;123(3):585-95
pubmed: 2513255