Helicobacter pylori bab paralog distribution and association with cagA, vacA, and homA/B genotypes in American and South Korean clinical isolates

Aeryun Kim, Stephanie L. Servetas, Jieun Kang, Jinmoon Kim, Sungil Jang, Ho Jin Cha, Wan Jin Lee, June Kim, Judith Romero-Gallo, Richard M. Peek, D. Scott Merrell, Jeong Heon Cha

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere0137078
JournalPloS one
Volume10
Issue number8
DOIs
Publication statusPublished - 2015 Aug 28

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Helicobacter pylori
Genes
Genotype
loci
genotype
Membrane Proteins
outer membrane proteins
Virulence Factors
Pathogens
virulence
genes
Geographic Locations
genetic variation
Gastric Mucosa
gastric mucosa
Population
Virulence
Disease Progression
disease course
genotyping

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kim, Aeryun ; Servetas, Stephanie L. ; Kang, Jieun ; Kim, Jinmoon ; Jang, Sungil ; Cha, Ho Jin ; Lee, Wan Jin ; Kim, June ; Romero-Gallo, Judith ; Peek, Richard M. ; Merrell, D. Scott ; Cha, Jeong Heon. / Helicobacter pylori bab paralog distribution and association with cagA, vacA, and homA/B genotypes in American and South Korean clinical isolates. In: PloS one. 2015 ; Vol. 10, No. 8.
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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.",
author = "Aeryun Kim and Servetas, {Stephanie L.} and Jieun Kang and Jinmoon Kim and Sungil Jang and Cha, {Ho Jin} and Lee, {Wan Jin} and June Kim and Judith Romero-Gallo and Peek, {Richard M.} and Merrell, {D. Scott} and Cha, {Jeong Heon}",
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Kim, A, Servetas, SL, Kang, J, Kim, J, Jang, S, Cha, HJ, Lee, WJ, Kim, J, Romero-Gallo, J, Peek, RM, Merrell, DS & Cha, JH 2015, 'Helicobacter pylori bab paralog distribution and association with cagA, vacA, and homA/B genotypes in American and South Korean clinical isolates', PloS one, vol. 10, no. 8, e0137078. https://doi.org/10.1371/journal.pone.0137078

Helicobacter pylori bab paralog distribution and association with cagA, vacA, and homA/B genotypes in American and South Korean clinical isolates. / Kim, Aeryun; Servetas, Stephanie L.; Kang, Jieun; Kim, Jinmoon; Jang, Sungil; Cha, Ho Jin; Lee, Wan Jin; Kim, June; Romero-Gallo, Judith; Peek, Richard M.; Merrell, D. Scott; Cha, Jeong Heon.

In: PloS one, Vol. 10, No. 8, e0137078, 28.08.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Helicobacter pylori bab paralog distribution and association with cagA, vacA, and homA/B genotypes in American and South Korean clinical isolates

AU - Kim, Aeryun

AU - Servetas, Stephanie L.

AU - Kang, Jieun

AU - Kim, Jinmoon

AU - Jang, Sungil

AU - Cha, Ho Jin

AU - Lee, Wan Jin

AU - Kim, June

AU - Romero-Gallo, Judith

AU - Peek, Richard M.

AU - Merrell, D. Scott

AU - Cha, Jeong Heon

PY - 2015/8/28

Y1 - 2015/8/28

N2 - 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.

AB - 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.

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