Abstract

Alteration of repeat tract length within the SSR of phase variable genes may enhance the persistence of isolates within their host for a long time (a period of months) (Alamro et al.,2014). Alamro et al. (2014) showed there was trend towards selection for OFF state or low expression for five phase variable genes (opc, hmbr, nadA, nalP, hpuAB) in three carriers (V54, V124 and V64) within strains belonging into CC174 and CC167 in first, second and third time points. He concluded that the selection for low or OFF state helped N. meningitidis to persist for a long time (Alamro et al., 2014). The current study aimed to detect the alteration in the repeat tracts of the same five variable genes within the previous three carriers (V54, V124, and V64) but for other strains belonging to CC22, CC269, and CC198 at the fourth time point. There was also a trend towards selection for an OFF state or low expression for three genes which are (opc, hpuAb, nalP) with 2/3 (66.6%) carriers while hmbr gene showed ON state in all carriers (100%). This indicates that antibodies formed against (opc, HpuAb, nalP) genes in strains belonging to CC174 and CC167 in first, second and third time points were able to enhance immunization against the isolates in the current study for CC269 and CC22 resulting in the selection for the OFF state or low expression. Conversely, antibodies formed against hmbr gene in the previous time points on isolates within the CC167 may not show immunization against hmbr gene in the isolates of current study CC22, CC198 and CC269 and so the gene stayed in the ON state. Interestingly, the nadA gene was missing from isolates under the current study. These results may reflect important aspects in the vaccination program especially as nadA is one of the component of Bexsero vaccine. Keywords: Phase variation, SSR, Neisseria meningitides.

Highlights

  • Phase variation is one of the adaptive strategies of pathogenic and commensal bacteria

  • Slipped strand mispairing of simple sequence repeats (SSR) during DNA replication leads to reversible changes in repeat number for tracts located in the open reading frame (ORF) or the promoter region of a gene

  • The LgtG product controlled addition of a glucose blocking addition of phosphoethanolamine to this specific position in LPS. These results indicated that phase variation mediates changes in the expression of lgtG resulting in variants that could escape an immune response and adaptation to a stress condition

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Summary

Introduction

Phase variation is one of the adaptive strategies of pathogenic and commensal bacteria. This process is characterized by hyper-mutation of DNA sequences or hypervariable methylation in particular regions of the genome sequence and in a reversible manner. Phase variation mechanisms include slipped strand mispairing, site-specific recombination, homologous recombination and epigenetic modification (Bayliss et al, 2008). The major mechanism utilised in Neisseria is slipped strand mispairing and so this will be the focus of this section. Slipped strand mispairing of simple sequence repeats (SSR) during DNA replication leads to reversible changes in repeat number for tracts located in the ORF or the promoter region of a gene. Mutability of the SSR is influenced by cis-acting factors such as repeat length and trans-acting factors such as DNA replication and repair factors (Moxon et al, 2006; Bayliss, 2009; Bayliss et al, 2001)

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