From The Cover: Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding

@article{citeulike:2320398, abstract = {Heterogeneity among Helicobacter pylori strains in gastric epithelial adherence is postulated to contribute to pathogen fitness in the physiologically diverse human population. H. pylori adherence to ABO and Lewis b (Leb) blood group antigens in the human stomach is mediated by the blood group antigen-binding adhesin BabA. Approximately 70\% of Swedish and U.S. H. pylori clinical isolates exhibit Leb binding, but here we show that the babA gene is present in each of 10 Leb-nonbinding strains. Fluorescence microscopy identified occasional bacterial cells with a Leb-binding phenotype in populations of Leb-nonbinding strains. Thus, nonbinding seemed to be a metastable phenotype. To model metastable transition into the virulence-associated Leb-binding mode, Leb-binding clones were isolated from nonadherent strains by panning with Leb-magnetic beads and characterized. Strain 17875 has two babA genes, babA1 (silent) and babA2 (expressed). We found that a babA2-cam derivative of strain 17875 regained Leb binding by recombination of the formerly silent babA1 gene into the expressed and partially homologous babB locus. The chimeric BabB/A adhesin binds Leb with an affinity similar to that of wild-type BabA adhesin, but its expression level was lower and was subject to phase variation through slipped-strand mispairing. Equivalent results were obtained with strain NCTC11638. We propose that adhesin metastability and heterogeneity contributes to bacterial fitness and results in some clones having potential for periodic activation and deactivation of virulence appropriate for intensity of the host response to infection. 10.1073/pnas.0404817101}, author = {Backstrom, Anna and Lundberg, Carina and Kersulyte, Dangeruta and Berg, Douglas E. and Boren, Thomas and Arnqvist, Anna }, citeulike-article-id = {2320398}, doi = {http://dx.doi.org/10.1073/pnas.0404817101}, journal = {Proceedings of the National Academy of Sciences}, keywords = {baba, pylori}, month = {November}, number = {48}, pages = {16923--16928}, posted-at = {2008-02-01 19:22:02}, priority = {2}, title = {From The Cover: Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding}, url = {http://dx.doi.org/10.1073/pnas.0404817101}, volume = {101}, year = {2004} }

TY - JOUR ID - citeulike:2320398 L3 - citeulike-article-id:2320398 TI - From The Cover: Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding JF - Proceedings of the National Academy of Sciences VL - 101 IS - 48 SP - 16923 EP - 16928 N2 - Heterogeneity among Helicobacter pylori strains in gastric epithelial adherence is postulated to contribute to pathogen fitness in the physiologically diverse human population. H. pylori adherence to ABO and Lewis b (Leb) blood group antigens in the human stomach is mediated by the blood group antigen-binding adhesin BabA. Approximately 70% of Swedish and U.S. H. pylori clinical isolates exhibit Leb binding, but here we show that the babA gene is present in each of 10 Leb-nonbinding strains. Fluorescence microscopy identified occasional bacterial cells with a Leb-binding phenotype in populations of Leb-nonbinding strains. Thus, nonbinding seemed to be a metastable phenotype. To model metastable transition into the virulence-associated Leb-binding mode, Leb-binding clones were isolated from nonadherent strains by panning with Leb-magnetic beads and characterized. Strain 17875 has two babA genes, babA1 (silent) and babA2 (expressed). We found that a babA2-cam derivative of strain 17875 regained Leb binding by recombination of the formerly silent babA1 gene into the expressed and partially homologous babB locus. The chimeric BabB/A adhesin binds Leb with an affinity similar to that of wild-type BabA adhesin, but its expression level was lower and was subject to phase variation through slipped-strand mispairing. Equivalent results were obtained with strain NCTC11638. We propose that adhesin metastability and heterogeneity contributes to bacterial fitness and results in some clones having potential for periodic activation and deactivation of virulence appropriate for intensity of the host response to infection. 10.1073/pnas.0404817101 KW - baba KW - pylori AU - Backstrom, Anna AU - Lundberg, Carina AU - Kersulyte, Dangeruta AU - Berg, Douglas AU - Boren, Thomas AU - Arnqvist, Anna PY - 2004/11/30/ UR - http://dx.doi.org/10.1073/pnas.0404817101 ER -