Expression of the BabA adhesin during experimental infection with Helicobacter pylori.
The Helicobacter pylori babA gene encodes an outer membrane protein that mediates binding to fucosylated ABH antigens of the ABO blood group. We recently demonstrated that BabA expression is lost during experimental infection of rhesus macaques with H. pylori J166. We sought to test the generality of this observation by comparison of different H. pylori strains and different animal hosts. Challenge of macaques with H. pylori J99 yielded output strains that lost BabA expression, either by selection and then expansion of a subpopulation of J99 that had a single-base-pair mutation that encoded a stop codon or by gene conversion of babA with a duplicate copy of babB, a paralog of unknown function. Challenge of mice with H. pylori J166, which unlike J99, has 5' CT repeats in babA, resulted in loss of BabA expression due to phase variation. In the gerbil, Leb binding was lost by replacement of the babA gene that encoded Leb binding with a nonbinding allele that differed at six amino acid residues. Complementation experiments confirmed that change in these six amino acids of BabA was sufficient to eliminate binding to Leb and to gastric tissue. These results demonstrate that BabA expression in vivo is highly dynamic, and the findings implicate specific amino acid residues as critical for binding to fucosylated ABH antigens. We hypothesize that modification of BabA expression during H. pylori infection is a mechanism to adapt to changing conditions of inflammation and glycan expression at the epithelial surface.
Styer
Cathy M
CM
Department of Medicine and Microbiology, Center for Comparative Medicine, University of California, Davis School of Medicine, Davis, California 95616, USA.
Hansen
Lori M
LM
Cooke
Cara L
CL
Gundersen
Amy M
AM
Choi
Sung Sook
SS
Berg
Douglas E
DE
Benghezal
Mohammed
M
Marshall
Barry J
BJ
Peek
Richard M
RM
Borén
Thomas
T
Solnick
Jay V
JV
D000220:Adaptation, Biological; D018829:Adhesins, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001422:Bacterial Adhesion; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA
D018829:Adhesins, Bacterial; C400429:BabA protein, Helicobacter pylori; D004269:DNA, Bacterial; C073899:adhesin, helicobacter