Fratricide activity of MafB protein of N. meningitidis strain B16B6

Abstract

BackgroundNeisseria meningitidis is an inhabitant of the mucosal surfaces of the human nasopharynx. We recently demonstrated that the secreted meningococcal Two-partner secretion protein A (TpsA) is involved in interbacterial competition. The C-terminal end of the large TpsA protein contains a small toxic domain that inhibits the growth of target bacteria. The producing cells are protected from this toxic activity by a small immunity protein that is encoded by the gene immediately downstream of the tpsA gene. Further downstream on the chromosome, a repertoire of toxic modules, designated tpsC cassettes, is encoded that could replace the toxic module of TpsA by recombination. Each tpsC cassette is associated with a gene encoding a cognate immunity protein.ResultsBlast searchers using the toxic domains of TpsA and TpsC proteins as queries identified homologies with the C-terminal part of neisserial MafB proteins, which, for the rest, showed no sequence similarity to TpsA proteins. On the chromosome, mafB genes are part of genomic islands, which include cassettes for additional toxic modules as well as genes putatively encoding immunity proteins. We demonstrate that a MafB protein of strain B16B6 inhibits the growth of a strain that does not produce the corresponding immunity protein. Assays in E. coli confirmed that the C-terminal region of MafB is responsible for toxicity, which is inhibited by the cognate immunity protein. Pull-down assays revealed direct interaction between MafB toxic domains and the cognate immunity proteins.ConclusionsThe meningococcal MafB proteins are novel toxic proteins involved in interbacterial competition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0493-6) contains supplementary material, which is available to authorized users.

Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization

“…Recent studies have demonstrated that mafB genes encode polymorphic toxins that provide an advantage in competition assays ( 28 , 29 ). In meningococcal strains, mafB genes are present on three Maf genomic islands, termed MGI-1, -2, and -3.…”

Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

“…TpsA induces persister formation upon direct contact with cells lacking sufficient levels of immunity protein [ 179 ]. Very likely, more recently discovered secretion systems that deliver toxins to the target cells [ 180 , 181 ] also contribute to biofilm formation and recalcitrance, a research area that needs to be addressed.…”

Molecular interactions betweenNeisseria meningitidisand its human host

“…Indeed, downstream of the full-length toxin gene and its cognate immunity gene, there is a variable number of 5′ truncated toxin genes called CT(C-terminal)-cassettes, also associated with their specific immunity gene (Arenas, Schipper, van Ulsen, van der Ende, & Tommassen, 2013;Jamet et al, 2015). These alternative toxic domains could potentially allow antigenic variation by recombination with the full-length toxin gene (i.e., mafB or tpsA; Arenas et al, 2013;Arenas et al, 2015;Jamet et al, 2015). Hence, CT-cassettes constitute a potential reservoir of toxic domains.…”