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Genomic features of the Helicobacter pylori strain PMSS1 and its virulence attributes as deduced from its in vivo colonisation patterns
Author(s) -
Dyer Victoria,
Brüggemann Holger,
Sörensen Meike,
Kühl Anja A.,
Hoffman Kirstin,
Brinkmann Volker,
Reines Maria del Mar,
Zimmerman Stephanie,
Meyer Thomas F.,
Koch Manuel
Publication year - 2018
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14123
Subject(s) - biology , caga , pathogenicity island , virulence , microbiology and biotechnology , gene , genetics , secretion , chromosomal translocation , helicobacter pylori , mutant , pathogen , virulence factor , genomic island , colonisation , coding region , colonization , biochemistry
Summary The human gastric pathogen Helicobacter pylori occurs in two basic variants, either exhibiting a functional cag PAI‐encoded type‐4‐secretion‐system (T4SS) or not. Only a few cag PAI‐positive strains have been successfully adapted for long‐term infection of mice, including the pre‐mouse Sydney strain 1 (PMSS1). Here we confirm that PMSS1 induces gastric inflammation and neutrophil infiltration in mice, progressing to intestinal metaplasia. Complete genome analysis of PMSS1 revealed 1,423 coding sequences, encompassing the cag PAI gene cluster and, unusually, the location of the cytotoxin‐associated gene A ( cag A) approximately 15 kb downstream of the island. PMSS1 harbours three genetically exchangeable loci that are occupied by the hopQ coding sequences. HopQ represents a critical co‐factor required for the translocation of CagA into the host cell and activation of NF‐κB via the T4SS. Long‐term colonisation of mice led to an impairment of cag PAI functionality. One of the bacterial clones re‐isolated at four months post‐infection revealed a mutation in the cag PAI gene cag W, resulting in a frame shift mutation, which prevented CagA translocation, possibly due to an impairment of T4SS function. Rescue of the mutant cag W re‐established CagA translocation. Our data reveal intriguing insights into the adaptive abilities of PMSS1, suggesting functional modulation of the H. pylori cag PAI virulence attribute.