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.
Highlights
The Gram-negative diplococcus Neisseria meningitidis is a common inhabitant of the human nasopharynx, but it is the causative agent of meningococcal disease, a life-threatening infection characterized by fast development of septicemia and/or meningitis
The sequences flanking the autB gene in H. influenzae strains, including the 5′ end of the holB gene and the 3′ end of the tmk gene are present as intergenic regions flanking autB in N. meningitidis and N. gonorrhoeae (Figure 1)
This distribution was earlier explained by the transfer of the gene from an unidentified microorganism to H. influenzae and to a recent ancestor of both N. meningitidis and N. gonorrhoeae (Davis et al, 2001)
Summary
The Gram-negative diplococcus Neisseria meningitidis is a common inhabitant of the human nasopharynx, but it is the causative agent of meningococcal disease, a life-threatening infection characterized by fast development of septicemia and/or meningitis. ATs are a class of proteins secreted by Gram-negative bacteria (Grijpstra et al, 2013) They contain an N-terminal signal sequence for transport across the inner membrane via the Sec machinery and a C-terminal translocator domain that inserts as a β-barrel in the outer membrane via the Bam complex and that assists in the translocation of an associated passenger domain across the outer membrane. The passenger can remain attached to the cell surface or it can be released into the external medium by one of a variety of possible proteolytic mechanisms. Their functions can be very diverse, but they are often involved in virulence (Grijpstra et al, 2013)
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