title: Helicobacter pylori bab Paralog Distribution and Association with cagA, vacA, and homA/B Genotypes in American and South Korean Clinical Isolates.
abstract: Helicobacter pylori genetic variation is a crucial component of colonization and persistence within the inhospitable niche of the gastric mucosa. As such, numerous H. pylori genes have been shown to vary in terms of presence and genomic location within this pathogen. Among the variable factors, the Bab family of outer membrane proteins (OMPs) has been shown to differ within subsets of strains. To better understand genetic variation among the bab genes and to determine whether this variation differed among isolates obtained from different geographic locations, we characterized the distribution of the Bab family members in 80 American H. pylori clinical isolates (AH) and 80 South Korean H. pylori clinical isolates (KH). Overall, we identified 23 different bab genotypes (19 in AH and 11 in KH), but only 5 occurred in greater than 5 isolates. Regardless of strain origin, a strain in which locus A and locus B were both occupied by a bab gene was the most common (85%); locus C was only occupied in those isolates that carried bab paralog at locus A and B. While the babA/babB/- genotype predominated in the KH (78.8%), no single genotype could account for greater than 40% in the AH collection. In addition to basic genotyping, we also identified associations between bab genotype and well known virulence factors cagA and vacA. Specifically, significant associations between babA at locus A and the cagA EPIYA-ABD motif (P<0.0001) and the vacA s1/i1/m1 allele (P<0.0001) were identified. Log-linear modeling further revealed a three-way association between bab carried at locus A, vacA, and number of OMPs from the HOM family (P<0.002). En masse this study provides a detailed characterization of the bab genotypes from two distinct populations. Our analysis suggests greater variability in the AH, perhaps due to adaptation to a more diverse host population. Furthermore, when considering the presence or absence of both the bab and homA/B paralogs at their given loci and the vacA genotype, an association was observed. Our results highlight the multifactorial nature of H. pylori mediated disease and the importance of considering how the specific combinations of H. pylori virulence genes and their multiple interactions with the host will collectively impact disease progression.
authors: Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, BK21 Plus Project, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Aeryun
authors: A
authors: Kim
authors: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland, 20814, United States of America.
authors: Stephanie L
authors: SL
authors: Servetas
authors: Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, BK21 Plus Project, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Jieun
authors: J
authors: Kang
authors: Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, BK21 Plus Project, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Jinmoon
authors: J
authors: Kim
authors: Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Sungil
authors: S
authors: Jang
authors: Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Ho Jin
authors: HJ
authors: Cha
authors: Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Wan Jin
authors: WJ
authors: Lee
authors: Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea.
authors: June
authors: J
authors: Kim
authors: Departments of Cancer Biology and Medicine, Vanderbilt University, Nashville, Tennessee, 37240, United States of America.
authors: Judith
authors: J
authors: Romero-Gallo
authors: Departments of Cancer Biology and Medicine, Vanderbilt University, Nashville, Tennessee, 37240, United States of America.
authors: Richard M
authors: RM
authors: Peek
authors: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland, 20814, United States of America.
authors: D Scott
authors: DS
authors: Merrell
authors: Department of Oral Biology, Oral Science Research Center, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, BK21 Plus Project, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Jeong-Heon
authors: JH
authors: Cha
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D060005:Genotyping Techniques; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D006761:Hospitals; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D056910:Republic of Korea; D012689:Sequence Homology, Nucleic Acid; D014481:United States
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C546056:HomB protein, Helicobacter pylori; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori