Slipped-Strand Mispairing in the Gene Encoding Sialidase NanH3 in Gardnerella spp.

Abstract

Cell wall proteins with sialidase activity are involved in carbohydrate assimilation, adhesion to mucosal surfaces, and biofilm formation. Gardnerella spp. inhabit the human vaginal microbiome and encode up to three sialidase enzymes, two of which are suspected to be cell wall associated. Here we demonstrate that the gene encoding extracellular sialidase NanH3 is found almost exclusively in G. piotii and closely related Gardnerella genome sp. 3, and its presence correlates with sialidase positive phenotype in a collection of 112 Gardnerella isolates. The nanH3 gene sequence includes a homopolymeric repeat of cytosines that varies in length within cell populations, indicating that this gene is subject to slipped-strand mispairing, a mechanisms of phase variation in bacteria. Variation in the length of the homopolymer sequence results in encoding of either the full length sialidase protein or truncated peptides lacking the sialidase domain due to introduction of reading-frame shifts and premature stop codons. Phase variation in NanH3 may be involved in immune evasion or modulation of adhesion to host epithelial cells, and formation of biofilms characteristic of the vaginal dysbiosis known as bacterial vaginosis.

Prognosis of recurrent bacterial vaginosis based on longitudinal changes in abundance of Lactobacillus and specific species of Gardnerella

“…Clade 2 isolates were uniquely and pervasively (9 of 9) positive for sialidase activity [ 29 ]. Confusion about the broader distribution of sialidase stemmed from the PCR based detection of the sialidase A gene; recent studies show that the major sialidase genes are encoded instead by NanH2 and NanH3, and reside only in clade 2 isolates [ 45 , 46 ]. The issue of whether differences in susceptibility to metronidazole is clade-specific has also met with mixed results.…”

Sialidase Activity in the Cervicovaginal Fluid Is Associated With Changes in Bacterial Components of Lactobacillus-Deprived Microbiota

“…Interestingly, although Gardnerella spp. are recognized as the main sialidase producers in the cervicovaginal environment ( Hardy et al., 2017 ; Kurukulasuriya et al., 2020 ), they were not figured out among the differently enriched taxa. Recently, it has been demonstrated that Gardnerella sialidase-encoding genes nanH2 and nanH3 are more restricted to some strains than previously thought ( Kurukulasuriya et al., 2020 ).…”

“…are recognized as the main sialidase producers in the cervicovaginal environment ( Hardy et al., 2017 ; Kurukulasuriya et al., 2020 ), they were not figured out among the differently enriched taxa. Recently, it has been demonstrated that Gardnerella sialidase-encoding genes nanH2 and nanH3 are more restricted to some strains than previously thought ( Kurukulasuriya et al., 2020 ). Thus, despite the fact that sialidases contribute for Gardnerella adherence and biofilm formation, these species are also highly abundant in sialidase-negative CFV samples ( Hardy et al., 2017 ).…”

“…However, Gardnerella spp. are considered the main source of this enzyme in the cervicovaginal environment ( Hardy et al., 2017 ; Kurukulasuriya et al., 2020 ). In fact, Gardnerella spp.…”

Cervicovaginal loads of Gardnerella spp. are increased in immunocompetent women with persistent high-risk human papillomavirus infection

“…One of the most important virulence factors for Gardnerella spp. is sialidase production [21,22]. Sialidases hydrolyze the sialic acid of the host's epithelial cells, exposing binding sites that facilitate bacterial adhesion to the epithelium, further facilitating the formation of biofilms [23][24][25].…”