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Polymorphisms in the genes encoding surface associated proteins of Clostridioides difficile isolates.

Amir Aliramezani1, Malihe Talebi2, Masoumeh Douraghi3

  • 1Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|October 20, 2020
PubMed
Summary

This study reveals significant genetic diversity in Clostridioides difficile surface-associated proteins (SAPs), highlighting variations in antigenicity and immunogenicity. These findings suggest SAPs are promising targets for new C. difficile therapies and vaccines.

Keywords:
Clostridioides difficilePolymorphismsSurface associated proteinscwp66cwp84fliCfliDslpA

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Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Clostridioides difficile toxins are well-studied, but variations in surface-associated proteins (SAPs) crucial for colonization remain largely unknown.
  • SAPs play a key role in the initial stages of bacterial infection and colonization.
  • Understanding SAP diversity is essential for developing effective interventions against C. difficile.

Purpose of the Study:

  • To investigate the genetic polymorphisms in genes encoding surface-associated proteins (SAPs) of Clostridioides difficile.
  • To analyze the diversity and sequence types of key SAPs, including slpA, fliC, fliD, cwp66, and cwp84.
  • To predict the in-silico antigenicity and immunogenicity of identified SAP variants.

Main Methods:

  • Amplification and sequencing of slpA, fliC, fliD, cwp66, and cwp84 genes from 65 C. difficile isolates.
  • Utilized VaxiJen and BcePred online servers for in-silico prediction of protein antigenicity and immunogenicity.
  • Comparative analysis of nucleotide sequences to identify different types and subtypes of SAP genes.

Main Results:

  • Identified predominant slpA sequence types (gr-01, hr-01, 078-01) and discovered novel slpA subtypes (smz-09-Ir, smz-010-Ir) and a new type (Ir-01).
  • Revealed significant sequence type diversity for fliC (7 types), fliD (5 types), cwp66 (5 types), and cwp84 (3 types).
  • In-silico analysis indicated FliC possesses the highest antigenicity, while SlpA and Cwp66 exhibit the highest immunogenicity.

Conclusions:

  • Demonstrated considerable nucleotide polymorphism within C. difficile SAP genes.
  • Highlighted significant diversity in the antigenicity and immunogenicity profiles of these surface proteins.
  • Concluded that C. difficile SAPs represent promising targets for the development of novel therapeutics and vaccines.