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PMID: 11705965 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Comparison of genetic divergence and fitness between two subclones of Helicobacter pylori.

Infection and immunity ·Vol. 69 ·No. 12 ·2001-12-00 ·Pages 7832-8

Björkholm B, Lundin A, Sillén A, Guillemin K, Salama N, Rubio C, Gordon JI, Falk P, Engstrand L

Abstract

Helicobacter pylori has a very plastic genome, reflecting its high rate of recombination and point mutation. This plasticity promotes divergence of the population by the development of subclones and presumably enhances adaptation to host niches. We have investigated the genotypic and phenotypic characteristics of two such subclones isolated from one patient as well as the genetic evolution of these isolates during experimental infection. Whole-genome genotyping of the isolates using DNA microarrays revealed that they were more similar to each other than to a panel of other genotyped strains recovered from different hosts. Nonetheless, they still showed significant differences. For example, one isolate (67:21) contained the entire Cag pathogenicity island (PAI), whereas the other (67:20) had excised the PAI. Phenotypic studies disclosed that both isolates expressed adhesins that recognized human histo-blood group Lewis(b) glycan receptors produced by gastric pit and surface mucus cells. In addition, both isolates were able to colonize, to equivalent density and with similar efficiency, germ-free transgenic mice genetically engineered to synthesize Lewis(b) glycans in their pit cells (12 to 14 mice/isolate). Remarkably, the Cag PAI-negative isolate was unable to colonize conventionally raised Lewis(b) transgenic mice harboring a normal gastric microflora, whereas the Cag PAI-positive isolate colonized 74% of the animals (39 to 40 mice/isolate). The genomic evolution of both isolates during the infection of conventionally raised and germ-free mice was monitored over the course of 3 months. The Cag PAI-positive isolate was also surveyed after a 10 month colonization of conventionally raised transgenic animals (n = 9 mice). Microarray analysis of the Cag PAI and sequence analysis of the cagA, recA, and 16S rRNA genes disclosed no changes in recovered isolates. Together, these results reveal that the H. pylori population infecting one individual can undergo significant divergence, creating stable subclones with substantial genotypic and phenotypic differences.

MeSH Terms
Adhesins, Bacterial Animals Antigens, Bacterial Bacterial Proteins/genetics Clone Cells Flagellin/genetics Genes, rRNA Genotype Germ-Free Life Helicobacter Infections/microbiology Helicobacter pylori/classification,genetics Humans Lewis Blood Group Antigens Mice Mice, Transgenic Oligonucleotide Array Sequence Analysis Oligosaccharides RNA, Ribosomal, 16S/genetics Rec A Recombinases/genetics Receptors, Immunologic Stomach/microbiology Stomach Diseases/microbiology
Chemicals
Adhesins, Bacterial Antigens, Bacterial Bacterial Proteins Lewis Blood Group Antigens Oligosaccharides RNA, Ribosomal, 16S Receptors, Immunologic bacterial adhesin receptor cagA protein, Helicobacter pylori galactopyranosyl-1-3-galactopyranosyl-1-3(4)-N-acetylglucosamine Flagellin flaA protein, bacteria Rec A Recombinases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Björkholm B
Swedish Institute for Infectious Disease Control, 171 82 Solna, Karolinska Institute, 171 77 Stockholm, Sweden.
Lundin A
Sillén A
Guillemin K
Salama N
Rubio C
Gordon J I
Falk P
Engstrand L
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.69.12.7832-7838.2001
Published
2001-12-00
Pages
7832-8
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC98879
Subset
IM
External Links
PubMed source DOI: 10.1128/IAI.69.12.7832-7838.2001 PMC Full Text View journal details
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