Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells

Abstract

Pili have been shown to play an essential role in the adhesion of Neisseria meningitidis to epithelial cells. However, among piliated strains, both inter- and intrastrain variability exist with respect to their degree of adhesion to epithelial cells in vitro (Virji et al., 1992). This suggests that factors other than the presence of pili per se are involved in this process. The N. meningitidis pilin subunit undergoes extensive antigenic variation. Piliated low- and high-adhesive derivatives of the same N. meningitidis strain were selected and the nucleotide sequence of the pilin gene expressed in each was determined. The highly adhesive derivatives had the same pilin sequence. The alleles encoding the pilin subunit of the low-adhesive derivatives were completely different from the one found in the high-adhesive isolates. Using polyclonal antibodies raised against one hyperadhesive variant, it was confirmed that the low-adhesive piliated derivatives expressed pilin variants antigenically different from the highly adhesive strains. The role of antigenic variation in the adhesive process of N. meningitidis was confirmed by performing allelic exchanges of the pilE locus between low- and high-adhesive isolates. Antigenic variation has been considered a means by which virulent bacteria evade the host immune system. This work provides genetic proof that a bacterial pathogen, N. meningitidis, can use antigenic variation to modulate their degree of virulence.

A two-component system is required for colonization of host cells by meningococcus

“…The strain used in this study is a derivative of the piliated, Opa 2 , Opc 2 , PilC1 + and PilC2 + serogroup C N. meningitidis 8013 strain (Nassif et al, 1993). N. meningitidis strains were grown on GC agar (GCB; Difco), supplemented with Kellogg's defined supplement (Kellogg et al, 1963) overnight at 37 uC in a moist atmosphere containing 5 % CO 2 .…”

Neisseria gonorrhoeae PilV, a type IV pilus-associated protein essential to human epithelial cell adherence

“…Similarly, receptor specificity of the sialic acid E. coli adhesin SfaS appears to be variable depending on the fimbrial subunit with which it is associated (31). Studies in pathogenic neisseria species have suggested a role for the pilin subunit PilE in epithelial cell interaction because changes in its primary structure arising via antigenic variation have been reported to influence adherence proficiencies and tissue tropism (12,(14)(15)(16). Given their structural identities in the amino terminal domains thought to be crucial to subunit-subunit contact, one explanation might relate to the differing capacities of altered PilE protein and PilV to interact productively with one another, leading to reduced or defective PilV activity.…”

“…However, several studies have suggested a role for the pilin subunit PilE in receptor recognition. These include numerous findings showing that different antigenic variant forms of PilE influence epithelial cell adherence and tissue tropism (12,(14)(15)(16). However, the structural and functional attributes of PilE accounting for these observations remain unknown.…”

Characterization of MDAΦ, a temperate filamentous bacteriophage of Neisseria meningitidis

“…Z5463 is a naturally transformable serogroup A strain that belongs to the same sequence type as strain Z2491 (Sarkari et al, 1994). N. meningitidis 8013 (2C4.3), a serogroup C strain (C : 22 : NST : L3,7,9), was also used in this study (Nassif et al, 1993).…”

“…Z5463(SB-aph39) was obtained following transformation of DNA of strain N. meningitidis 8013 SB-aph39 mutant (kanamycin resistant) (Nassif et al, 1993) into Z5463. Both strains Z5463orf6-aph39 and Z5463orf6 : : aph39 were constructed by an overlapping method using the oligonucleotides listed in Table 2.…”