The cag pathogenicity island of Helicobacter pylori is disrupted in the majority of patient isolates from different human populations.
The cag pathogenicity island (cag-PAI) is one of the major virulence determinants of Helicobacter pylori. The chromosomal integrity of this island or the lack thereof is speculated to play an important role in the progress of the gastroduodenal pathology caused by H. pylori. We determined the integrity of the cag-PAI by using specific flanking and internally anchored PCR primers to know the biogeographical distribution of strains carrying fully integral cag-PAI with proinflammatory behavior in vivo. Genotypes based on eight selected loci were studied in 335 isolates obtained from eight different geographic regions. The cag-PAI appeared to be disrupted in the majority of patient isolates throughout the world. Conservation of cag-PAI was highest in Japanese isolates (57.1%). However, only 18.6% of the Peruvian and 12% of the Indian isolates carried an intact cag-PAI. The integrity of cag-PAI in European and African strains was minimal. All 10 strains from Costa Rica had rearrangements. Overall, a majority of the strains of East Asian ancestry were found to have intact cag-PAI compared to strains of other descent. We also found that the cagE and cagT genes were less often rearranged (18%) than the cagA gene (27%). We attempted to relate cag-PAI rearrangement patterns to disease outcome. Deletion frequencies of cagA, cagE, and cagT genes were higher in benign cases than in isolates from severe ulcers and gastric cancer. Conversely, the cagA promoter and the left end of the cag-PAI were frequently rearranged or deleted in isolates linked to severe pathology. Analysis of the cag-PAI genotypes with a different biogeoclimatic history will contribute to our understanding of the pathogen-host interaction in health and disease.
Kauser
Farhana
F
Pathogen Evolution Group, Center for DNA Fingerprinting and Diagnostics, Hyderabad 500 076, India.
Khan
Aleem A
AA
Hussain
M Abid
MA
Carroll
Ian M
IM
Ahmad
Naheed
N
Tiwari
Santosh
S
Shouche
Yogesh
Y
Das
Bimal
B
Alam
Mahfooz
M
Ali
S Mahaboob
SM
Habibullah
C M
CM
Sierra
Rafaela
R
Megraud
Francis
F
Sechi
Leonardo A
LA
Ahmed
Niyaz
N
D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism; D001208:Asia / Q000453:epidemiology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003364:Costa Rica / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D017353:Gene Deletion; D005838:Genotype; D016481:Helicobacter Infections / Q000453:epidemiology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D016133:Polymerase Chain Reaction; D013019:South Africa / Q000453:epidemiology; D014774:Virulence
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C103937:PicB protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori