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Short Communication
Identifcation and Characterization of Aminopeptidase N
1 Gene of the Indian Malaria Vector Anopheles culicifacies
(Diptera: Culicidae)
Renu Jakhar
1,
and Surendra Kumar Gakhar
Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak-124001, Haryana, India and
1
Corresponding author,
e-mail: renujakhar22@gmail.com
Subject Editor: Michel Slotman
Received 30 June 2020; Editorial decision 4 January 2021
Abstract
Aminopeptidase N1 (APN) is one of the important enzymes involved in blood digestion and is up-regulated
along with several other enzymes in response to bloodmeal ingestion. APN is a zinc metalloprotease that
cleaves one amino acid residue at a time from the amino terminus of the protein. The APN1 gene of the
Indian malaria vector Anopheles culicifacies Giles was cloned and characterized. The An. culicifacies APN1
(AcAPN1) gene has an Open Reading Frame of 3084 basepairs which encodes a putative protein of 1027
amino acids. The coding region of the gene shares 81% and 78% similarity to the APN1 genes found in An.
stephensi (Diptera: Culicidae) and An. gambiae (Diptera: Culicidae), respectively. The organization of the
APN1 gene was studied in available mosquito genomes and a three-dimensional structure of AcAPN1 mod-
eled using homology structure modeling. The enzymatic active site was predicted to consist of HEYAH and
GAMEN amino acid residues, and a comparison of the protein sequences among different genera revealed
the conservation of zinc-binding residues. The expression pattern of AcAPN1 showed that the gene was
expressed rapidly in response to the ingestion of the bloodmeal and therefore this gene may be used to
exploit its promoter region as an antiparasite candidate molecule.
Key words: mosquito, Anopheles culicifacies, Aminopeptidase N1
Malaria continues to impose a huge health burden mostly on popu-
lations residing in tropical and semitropical regions of the world.
Genetic modifcation of malaria vectors is one promising interven-
tion. Accordingly, the genes that permit malarial infection in mos-
quito vectors can be identifed and then replaced or altered in terms
of their function and thereby disrupt Plasmodium development in
the vector. In this way, vector Anopheles populations will become
refractory to the parasite, eventually leading to malaria transmis-
sion being halted. The path for the creation of such mosquitoes faces
many challenges. The expression of a transgene in the mosquito
requires the use of an appropriate promoter. Interruption of the
parasite developmental process in the mosquito using antiparasite
transgenic strategies generally focuses on three different sites within
the mosquito: midgut, hemolymph, and salivary glands. The mos-
quito midgut probably provides the more fruitful results, because it
is the site where parasite syngamy occurs, followed by infection and
then asexual reproduction. The Aminopeptidase N (APN) is known
to facilitate the malaria parasite invasion into midgut and is perhaps
the most important vector/mosquito-based Transmission Blocking
Vaccine candidate (Mathias et al. 2012, Wangdi et al. 2016).
Antibodies against a midgut aminopeptidase (AgAPN1) reduced
P. falciparum oocyst infection intensity in An. gambiae Giles and
An. stephensi Liston by 73% and 67%, respectively (Dinglasan et al.
2007, Armistead et al. 2014). In India, An. culicifacies A (Diptera:
Culicidae) is an important vector of malaria. It is responsible for
60–70% of malaria cases every year (Goswami et al. 2006); how-
ever, the blood inducible APN1 gene has yet to be characterized.
This study describes the cloning and expression pattern of the An.
culicifacies A APN1 gene, and the in silico analysis of the related
protein to APN1 gene.
Materials and Methods
Mosquitoes Rearing
Anopheles culicifacies A (Dhera strain) was used in this study. This
strain was obtained from the National Institute of Malaria Research
(NIMR), New Delhi. The mosquitoes were reared in an insectary
maintained at 28 ± 2°C and 70%–80% relative humidity, with sim-
ulated dawn and dusk and 14L: 10D photoperiod (Kumar et al.
2014).
Journal of Medical Entomology, 58(3), 2021, 1476–1481
doi: 10.1093/jme/tjab011
Advance Access Publication Date: 4 March 2021
Short Communication
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