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Role of FNR and FNR‐regulated, sugar fermentation genes in Neisseria meningitidis infection
Author(s) -
Bartolini Erika,
Frigimelica Elisabetta,
Giovinazzi Serena,
Galli Giuliano,
Shaik Yazdani,
Genco Caroline,
Welsch Jo Anne,
Granoff Dan M.,
Grandi Guido,
Grifantini Renata
Publication year - 2006
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/j.1365-2958.2006.05163.x
Subject(s) - biology , regulon , neisseria meningitidis , operon , microbiology and biotechnology , gene , fermentation , mutant , transcriptome , bacteria , gene expression , genetics , biochemistry
Summary While it is generally accepted that anaerobic metabolism is required during infection, supporting experimental data have only been described in a limited number of studies. To provide additional evidence on the role of anaerobic metabolism in bacterial pathogens while invading mammalian hosts, we analysed the effect of the inactivation of FNR, the major regulatory protein involved in the adaptation to oxygen restrictive conditions, and of two of the FNR‐regulated genes on the survival of Neisseria meningitidis serogroup B ( MenB ) in vivo . We found that fnr deletion resulted in more than 1 log reduction in the meningococcal capacity to proliferate both in infant rats and in mice. To identify which of the FNR‐regulated genes were responsible for this attenuated phenotype, we defined the FNR regulon by combining DNA microarray analysis and FNR–DNA binding studies. Under oxygen‐restricted conditions, FNR positively controlled the transcription of nine transcriptional units, the most upregulated of which were the two operons NMB0388‐ galM and mapA‐pgmβ implicated in sugar metabolism and fermentation. When galM and mapA were knocked out, the mutants were attenuated by 2 and 3 logs respectively. As the operons are controlled by FNR, from these data we conclude that MenB survival in the host anatomical sites where oxygen is limiting is supported by sugar fermentation.