Expression of the Gene for Autotransporter AutB of Neisseria meningitidis Affects Biofilm Formation and Epithelial Transmigration

Abstract

Neisseria meningitidis is a Gram-negative bacterium that resides as a commensal in the upper respiratory tract of humans, but occasionally, it invades the host and causes sepsis and/or meningitis. The bacterium can produce eight autotransporters, seven of which have been studied to some detail. The remaining one, AutB, has not been characterized yet. Here, we show that the autB gene is broadly distributed among pathogenic Neisseria spp. The gene is intact in most meningococcal strains. However, its expression is prone to phase variation due to slipped-strand mispairing at AAGC repeats located within the DNA encoding the signal sequence and is switched off in the vast majority of these strains. Moreover, various genetic disruptions prevent autB expression in most of the strains in which the gene is in phase indicating a strong selection against AutB synthesis. We observed that autB is expressed in two of the strains examined and that AutB is secreted and exposed at the cell surface. Functionality assays revealed that AutB synthesis promotes biofilm formation and delays the passage of epithelial cell layers in vitro. We hypothesize that this autotransporter is produced during the colonization process only in specific niches to facilitate microcolony formation, but its synthesis is switched off probably to evade the immune system and facilitate human tissue invasion.

Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection

“…The cargo domain of the NTHI Lav is predicted to remain membrane tethered and has a helix-turn-helix motif, suggesting a potential role for binding to extracellular DNA. A closely related ortholog in Neisseria meningitidis promotes biofilm formation and reduces transmigration through epithelial cells (Arenas et al, 2016). The observation that a Lav ortholog reduces invasion is consistent with our observation of increased IBC formation in the OM-adapted strains that are primarily in the OFF status.…”

Phase-variable bacterial loci: how bacteria gamble to maximise fitness in changing environments

“…MspA is expressed at high levels during invasive disease, [39,40] and is required for adhesion to human epithelial and endothelial cells [41]. The AutB adhesin switches ON-OFF due to changes in the length of an AAGC (n) SSR tract in its ORF [42]. Expression of AutB results in increased biofilm formation, but when phase-varied OFF, N. meningitidis is able to cross epithelial layers at a higher rate [42].…”

“…The AutB adhesin switches ON-OFF due to changes in the length of an AAGC (n) SSR tract in its ORF [42]. Expression of AutB results in increased biofilm formation, but when phase-varied OFF, N. meningitidis is able to cross epithelial layers at a higher rate [42]. AutB is highly immunogenic, so switching OFF of expression would also allow evasion of an immune response.…”

Characterization and Distribution of the autB Gene in Neisseria meningitidis

“…Other than the former four monomeric ATs, AutA is not secreted into the milieu of the bacteria and it also participates in autoaggregation (Arenas et al, 2015 ; Arenas and Tommassen, 2017 ). In contrast, the passenger domain of AutB is secreted but the AutB is still attached to the cell surface due to the translocator domain (Arenas et al, 2016 ).…”

“…A detailed study has elucidated the expression of the autB gene in N. meningitidis , whereby the mechanism of AutB appears to affect biofilm formation and epithelial transmigration (Arenas et al, 2016 ). A comprehensive analysis of AutB has been conducted and it complements the study of AutB, which has firmly assessed the ATs (Arenas et al, 2016 ). The distribution of the autB gene is well-known in the two pathogenic Neisseria spp.…”