Two-Partner Secretion Systems of Neisseria meningitidis Associated with Invasive Clonal Complexes

Abstract

The two-partner secretion (TPS) pathway is widespread among gram-negative bacteria and facilitates the secretion of very large and often virulence-related proteins. TPS systems consist of a secreted TpsA protein and a TpsB protein involved in TpsA transport across the outer membrane. Sequenced Neisseria meningitidis genomes contain up to five TpsA-and two TpsB-encoding genes. Here, we investigated the distribution of TPS-related open reading frames in a collection of disease isolates. Three distinct TPS systems were identified among meningococci. System 1 was ubiquitous, while systems 2 and 3 were significantly more prevalent among isolates of hyperinvasive clonal complexes than among isolates of poorly invasive clonal complexes. In laboratory cultures, systems 1 and 2 were expressed. However, several sera from patients recovering from disseminated meningococcal disease recognized the TpsAs of systems 2 and 3, indicating the expression of these systems during infection. Furthermore, we showed that the major secreted TpsAs of systems 1 and 2 depend on their cognate TpsBs for transport across the outer membrane and that the system 1 TpsAs undergo processing. Together, our data indicate that TPS systems may contribute to the virulence of N. meningitidis.

Role of HrpA in Biofilm Formation of Neisseria meningitidis and Regulation of the hrpBAS Transcripts

“…We are unsure of the reason why HrpA remains surface bound in our study, while studies from other groups found HrpA in the supernatant (42,48). It may be because the previous studies grew their cultures to ODs that most likely represented stationary-phase organisms, while ours were still in the log phase of growth.…”

“…1). This doublet band was described previously in Western blots of HrpA (48). Growth in anaerobic conditions consistently demonstrated a significant decrease in the intensity of the 220-kDa band (Fig.…”

“…Also, since the 6-h biofilms on HBE cells were equivalent, this implies a role for HrpA in the evolving structure of the biofilm and not necessarily as an adhesin in our model system (42). In contrast to previous publications, our Western blot studies of strains NMB, MC58, and C311 failed to demonstrate the secretion of HrpA into the supernatant of aerobically shaken broth cultures (42,48). We performed fluorescence microscopy to determine if the HrpA protein was present on the surface of strain NMB.…”

“…Recently, a type V secretion system was described in N. meningitidis (42,46,48). There are two categories of type V secretion in gram-negative organisms.…”

Comparative Genome Biology of a Serogroup B Carriage and Disease Strain Supports a Polygenic Nature of Meningococcal Virulence

“…The induction of the meningococcal outer membrane proteins upon contact with host cells, however, occurs in a time-dependent manner (25), and it is plausible that their induction takes place at earlier time points that were not investigated in this study. Finally, the high variability in the genetic architecture of the RTX, TPS, and maf loci together with the high sequence diversity of the encoded orthologous proteins supports an important role for these classes of genes in meningococcal infection biology; however, this remains to be fully resolved (53,55,63,81).…”