Identification of 2 hypothetical genes involved in Neisseria meningitidis cathelicidin resistance.
Cathelicidins play a pivotal role in innate immunity, providing a first barrier against bacterial infections at both mucosal and systemic sites. In this work, we have investigated the mechanisms by which Neisseria meningitidis serogroup B (MenB) survives at the physiological concentrations of human and mouse cathelicidin LL37 and CRAMP, respectively. By analyzing the global transcription profile of MenB in the presence or absence of CRAMP, 21 genes were found to be differentially expressed. Among these genes, the hypothetical genes NMB0741 and NMB1828 were up-regulated. When either of the 2 genes was deleted, MenB resistance to cathelicidins was impaired in vitro. Furthermore, the deletion of either of the 2 genes substantially reduced MenB virulence, as measured by the number of bacteria found in the blood of infected animals. Altogether, these results indicate that NMB0741 and NMB1828 are novel genes that have never been described before and that are involved in MenB cathelicidin resistance.
Frigimelica
Elisabetta
E
Novartis Vaccines, Siena, Italy.
Bartolini
Erika
E
Galli
Giuliano
G
Grandi
Guido
G
Grifantini
Renata
R
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology; D015153:Blotting, Western; D054804:Cathelicidins; D004352:Drug Resistance, Microbial; D005260:Female; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008585:Meningitis, Meningococcal / Q000188:drug therapy / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D038541:Neisseria meningitidis, Serogroup B / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D020411:Oligonucleotide Array Sequence Analysis; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D012329:RNA, Bacterial; D011994:Recombinant Proteins