Journal Article

Domain exchange at the 3’ end of the gene encoding the fratricide meningococcal two-partner secretion protein A

Tommassen, Jan, van der Ende, Arie, Schipper, Kim, van Ulsen, Peter, Arenas, Jesús

2013

Overview

Background Two-partner secretion systems in Gram-negative bacteria consist of an outer membrane protein TpsB that mediates the secretion of a cognate TpsA protein into the extracellular milieu. TpsA proteins have diverse, often virulence-related functions, and some of them inhibit the growth of related bacteria. In Neisseria meningitidis , several functions have been attributed to the TpsA proteins. Downstream of the tpsB and tpsA genes, several shorter tpsA -related gene cassettes, called tpsC , are located interspersed with intervening open-reading frames (IORFs). It has been suggested that the tpsC cassettes may recombine with the tpsA gene as a mechanism of antigenic variation. Here, we investigated (i) whether TpsA of N. meningitidis also has growth-inhibitory properties, (ii) whether tpsC cassettes recombine with the tpsA gene, and (iii) what the consequences of such recombination events might be. Results We demonstrate that meningococcal TpsA has growth-inhibitory properties and that the IORF located immediately downstream of tpsA confers immunity to the producing strain. Although bioinformatics analysis suggests that recombination between tpsC cassettes and tpsA occurs, detailed analysis of the tpsA gene in a large collection of disease isolates of three clonal complexes revealed that the frequency is very low and cannot be a mechanism of antigenic variation. However, recombination affected growth inhibition. In vitro experiments revealed that recombination can be mediated through acquirement of tpsC cassettes from the environment and it identified the regions involved in the recombination. Conclusions Meningococcal TpsA has growth-inhibitory properties. Recombination between tpsA and tpsC cassettes occurs in vivo but is rare and has consequences for growth inhibition. A recombination model is proposed and we propose that the main goal of recombination is the collection of new IORFs for protection against a variety of TpsA proteins.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Animal Genetics and Genomics / Bacteria / Bacterial Outer Membrane Proteins - genetics / Bacterial Secretion Systems - genetics / Bacteriology / Bioinformatics / Biomedical and Life Sciences / DNA, Bacterial - genetics / Genes / Genetic aspects / Genetic research / Genomics / Gram-negative bacteria / Health aspects / Life Sciences / Medical research / Microarrays / Microbial Genetics and Genomics / Microbiology / Neisseria meningitidis / Neisseria meningitidis - genetics / Neisseria meningitidis - growth & development / Open Reading Frames / Plant Genetics and Genomics / Prokaryote microbial genomics / Proteomics / Recombination, Genetic / Research Article / Sequence Analysis, DNA