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Growth deficiencies of Neisseria meningitidis pfs and luxS mutants are not due to inactivation of quorum sensing.
Heurlier, Karin; Vendeville, Agnès; Halliday, Nigel; Green, Andrew; Winzer, Klaus; Tang, Christoph M; Hardie, Kim R.
Afiliação
  • Heurlier K; Institute of Infection, Inflammation and Immunity, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom. Karin.heurlier@nottingham.ac.uk
J Bacteriol ; 191(4): 1293-302, 2009 Feb.
Article em En | MEDLINE | ID: mdl-19074394
ABSTRACT
The activated methyl cycle (AMC) is a central metabolic pathway used to generate (and recycle) several important metabolites and enable methylation. Pfs and LuxS are considered integral components of this pathway because they convert S-adenosylhomocysteine (SAH) to S-ribosylhomocysteine (SRH) and S-ribosylhomocysteine to homocysteine (HCY), respectively. The latter reaction has a second function since it also generates the precursor of the quorum-sensing molecule autoinducer 2 (AI-2). By demonstrating that there was a complete lack of AI-2 production in pfs mutants of the causative agent of meningitis and septicemia, Neisseria meningitidis, we showed that the Pfs reaction is the sole intracellular source of the AI-2 signal. Analysis of lacZ reporters and real-time PCR experiments indicated that pfs is expressed constitutively from a promoter immediately upstream, and careful study of the pfs mutants revealed a growth defect that could not be attributed to a lack of AI-2. Metabolite profiling of the wild type and of a pfs mutant under various growth conditions revealed changes in the concentrations of several AMC metabolites, particularly SRH and SAH and under some conditions also HCY. Similar studies established that an N. meningitidis luxS mutant also has metabolite pool changes and growth defects in line with the function of LuxS downstream of Pfs in the AMC. Thus, the observed growth defect of N. meningitidis pfs and luxS mutants is not due to quorum sensing but is probably due to metabolic imbalance and, in the case of pfs inactivation, is most likely due to toxic accumulation of SAH.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Liases de Carbono-Enxofre / Proteínas de Bactérias / Regulação Bacteriana da Expressão Gênica / Percepção de Quorum / Neisseria meningitidis / N-Glicosil Hidrolases Idioma: En Revista: J Bacteriol Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Liases de Carbono-Enxofre / Proteínas de Bactérias / Regulação Bacteriana da Expressão Gênica / Percepção de Quorum / Neisseria meningitidis / N-Glicosil Hidrolases Idioma: En Revista: J Bacteriol Ano de publicação: 2009 Tipo de documento: Article