Protein secretion and secreted proteins in pathogenicNeisseriaceae

Abstract

Secreted proteins of pathogenic bacteria are often essential virulence factors. They are involved, for example, in the adherence of the bacteria to host cells or required to suppress the host's defence mechanisms. Until recently, only IgA1 protease had been studied in detail in the NeisseriaceaeNeisseria meningitidis and Neisseria gonorrhoeae. The availability of their genome sequences, however, has boosted research in this area. Here, we present a survey of the secretome of the pathogenic Neisseriaceae, based on the available genome sequences, and the current knowledge of the functions and structures of the secreted proteins. Of the six protein-secretion pathways that are widely disseminated among Gram-negative bacteria, three pathways appear to be present among the Neisseriaceae, i.e. the autotransporter-, the two-partner- and the type I-secretion mechanisms. Comparison of the predicted secretomes reveals a considerable flexibility. As compared with N. meningitidis and the nonpathogen N. lactamica, N. gonorrhoeae appears to have a considerably degenerated secretome, which may reflect its altered niche occupancy. The flexibility of the secretome may be enhanced by the presence of ORFs in the genomes potentially encoding fragments of secreted proteins. We hypothesize that these ORFs may substitute for the corresponding fragments in the full-length genes through genetic recombination, thereby changing the host-cell receptor specificity of the secreted protein.

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

“…To establish phylogenetic relationships, we performed cluster analyses using the TPS ORFs identified in the sequenced genomes of N. meningitidis and of N. gonorrhoeae FA1090 and N. lactamica ST-640 ( Table 2). The tpsA genes were clustered using the parts encoding the TPS domains, the most conserved sequences within the tpsA genes (21). The domains were identified based upon their homology to the crystallized TPS domain of filamentous hemagglutinin of Bordetella pertussis (5).…”

“…1A). It has been hypothesized previously that the 3Ј ends of the tpsA genes may vary through genetic recombination with these cassettes (2,21).…”

“…The sequenced genomes of N. meningitidis strains Z2491 (14), FAM18 (2), and 053442 (15) encode a single TPS system on a genetic island, but the tpsA of strain 054432 is disrupted by a premature stop codon due to a single nucleotide mutation. The sequenced genome of strain MC58 (18) contains two copies of the genetic island, likely as the result of a duplication event (21). Both copies contain ORFs encoding TpsBs and TpsAs, namely, NMB1780 and NMB1779 on island 1 and NMB0496 and NMB0497 on island 2 (see Fig.…”

“…An N. meningitidis TPS system was initially identified by subtractive hybridization of genomic DNA of N. meningitidis strain Z2491 and Neisseria gonorrhoeae strain FA1090 (12). Analyses of genome sequences identified TpsAand TpsB-encoding open reading frames (ORFs) in N. meningitidis (2,14,18,21) and Neisseria lactamica, as well as disrupted ORFs in N. gonorrhoeae (21). The sequenced genomes of N. meningitidis strains Z2491 (14), FAM18 (2), and 053442 (15) encode a single TPS system on a genetic island, but the tpsA of strain 054432 is disrupted by a premature stop codon due to a single nucleotide mutation.…”

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

“…For example, at the cMME-bfrAlipA locus MC58 contains six genes (NMB1209 to NMB1214) that are absent from ␣710 (TPS in Fig. 2) and code for, among others, a TpsA protein (TpsA3/ NMB1214) and a repeat-in-toxin (RTX) activating protein (NMB1210) (82). At MME-pglC, in addition to pglB, the genome of ␣710 (comprising NMBB_2071 to NMBB_2074) contains further genes for glycosyl transferases that are involved in the glycosylation of type IV pili (Tfp) (35), and therefore Tfp glycosylation might be different in both strains.…”