The hookworm Ancylostoma ceylanicum intestinal transcriptome provides a platform for selecting drug and vaccine candidates.
BACKGROUND
The intestine of hookworms contains enzymes and proteins involved in the blood-feeding process of the parasite and is therefore a promising source of possible vaccine antigens. One such antigen, the hemoglobin-digesting intestinal aspartic protease known as Na-APR-1 from the human hookworm Necator americanus, is currently a lead candidate antigen in clinical trials, as is Na-GST-1 a heme-detoxifying glutathione S-transferase.


METHODS
In order to discover additional hookworm vaccine antigens, messenger RNA was obtained from the intestine of male hookworms, Ancylostoma ceylanicum, maintained in hamsters. RNA-seq was performed using Illumina high-throughput sequencing technology. The genes expressed in the hookworm intestine were compared with those expressed in the whole worm and those genes overexpressed in the parasite intestine transcriptome were further analyzed.


RESULTS
Among the lead transcripts identified were genes encoding for proteolytic enzymes including an A. ceylanicum APR-1, but the most common proteases were cysteine-, serine-, and metallo-proteases. Also in abundance were specific transporters of key breakdown metabolites, including amino acids, glucose, lipids, ions and water; detoxifying and heme-binding glutathione S-transferases; a family of cysteine-rich/antigen 5/pathogenesis-related 1 proteins (CAP) previously found in high abundance in parasitic nematodes; C-type lectins; and heat shock proteins. These candidates will be ranked for downstream antigen target selection based on key criteria including abundance, uniqueness in the parasite versus the vertebrate host, as well as solubility and yield of expression.


CONCLUSIONS
The intestinal transcriptome of A. ceylanicum provides useful information for the identification of proteins involved in the blood-feeding process, representing a first step towards a reverse vaccinology approach to a human hookworm vaccine.
Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
Junfei
J
Wei
Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
Ashish
A
Damania
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, 63108, USA.
Xin
X
Gao
Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
Zhuyun
Z
Liu
Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
Rojelio
R
Mejia
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, 63108, USA.|Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63108, USA.
Makedonka
M
Mitreva
Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
Ulrich
U
Strych
Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.|Department of Biology, Baylor University, Waco, TX, 76706, USA.
Maria Elena
ME
Bottazzi
Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.|Department of Biology, Baylor University, Waco, TX, 76706, USA.
Peter J
PJ
Hotez
Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. bzhan@bcm.edu.
Bin
B
Zhan
Ancylostoma ceylanicum; Hookworm; Intestine; Transcriptome; Vaccine candidate
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