Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Abstract
The genetic diversity and evolution of homD, coding for Helicobacter pylori outer
membrane protein (OMP) was investigated in a panel of approximately 200
clinical and reference strains, isolated from patients from different geographical
origins and presenting different gastric diseases. PCR, sequencing and bioinformatics
analyses were used.
The homD gene was present in all strains, at a conserved locus, and showed a low
genomic diversity, displaying high similarity at both nucleotide and amino acid
level. A similarity plot analysis also showed a high level of sequence conservation,
although a small region (~30 nucleotides) differed between Western strains and
the other strains (East Asian/Ameridian and African). This region was also found
in some allelic variants of another hom family member, the homC gene,
suggesting the existence of recombination events between these two OMP
encoding genes.
Sequence analysis of the HomD predicted protein showed a N terminus region
with a variable number of KP motif repeats (2 9 KP), with a correlation between
the lowest number of KP motif repeats (£4 KP) and peptic ulcer disease and the
highest number of repeats (£7 KP) and gastritis. In silico analysis of the HomD
protein showed that the region of KP motif repeats exhibits a strong hydrophilicity
and antigenicity and a high probability of being exposed to the bacterial surface,
suggesting that HomD is immunogenic.
These results suggest that homD gene is an important H. pylori antigen and,
because of its high global conservation, it is likely to constitute a new vaccine
target