title: Cell elongation and cell death of helicobacter pylori is modulated by the disruption of cdrA (cell division-related gene A).
abstract: The cell division-related gene A (cdrA) of Helicobacter pylori is dispensable in vivo and unique in having a repressive role on cell division and long-term survival. To clarify its role, comparisons of the wildtype HPK5 and isogenic cdrA-disrupted mutant HPKT510 were examined by ultrastructural morphology, PBP profiles, and susceptibility to beta-lactam antibiotics during long-term cultivation. Ultrastructural analyses revealed that the shorter rods of HPKT510 had a slightly wider periplasmic space between the inner and the outer membrane than those of HPK5. Cell division of HPKT510 cells was complete even under high-salt conditions in which HPK5 cells became filamentous due to inhibition of division. The filamentous HPK5 cells constructed an inner membrane without a cell wall at the presumed division site. After 4 days of cultivation (the late stationary phase), most of the HPK5 cells turned into ghosts and aggregates, while some of the HPKT510 cells remained as curved rods, which coincided with the results of cell viability. HPKT510 cells became resistant to ampicillin killing compared to HPK5 cells, although their minimum inhibitory concentrations (MICs) and PBP profiles were not significantly different. These results suggest that the cdrA product represses cell division via inhibiting cell wall synthesis at division site. During infection in both mice and humans, inactivation of cdrA eventually gains biological aspects such as increased viability, long-term survival and tolerance to antibiotics and high-salt condition, which might enhance a persistent infection.
authors.affiliation: Department of Clinical Laboratory Medicine, Kochi University School of Medicine, Nankoku, Kochi, Japan. htake@med.kochi-u.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Teruko
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Shirai
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kimoto
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Nishioka
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Con
authors.forename: Norihito
authors.initials: N
authors.lastname: Morimoto
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sugiura
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D016480:Helicobacter pylori / Q000166:cytology* / Q000187:drug effects / Q000235:genetics* / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009154:Mutation; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C114796:CdrA protein, Helicobacter pylori; D018797:Cell Cycle Proteins; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams