Genetic variability of IgA1 gene in Streptococcus pneumoniae of African serotype 1 in Sub-Saharan Africa

Abstract

Streptococcus pneumoniae is a significant causative agent of respiratory and central nervous system infections that exhibits considerable genomic diversity. The IgA1 gene is responsible for encoding IgA1 proteases which cleave human immunoglobulin and thus enhancing the pathogen’s ability to evade the host immune system and thus cause infections. This study aims to explore the genetic variability of the IgA1 protease gene in S. pneumoniae of the highly virulent and prevalent serotype 1 in Sub-Saharan Africa. Leveraging publicly genomic datasets, a bioinformatics based analysis was conducted to understand the magnitude of IgA1 gene variability across different geographical regions. The study involves full length 36 DNA sequences of IgA1 gene retrieved from public genomic databases based on availability from Sub-Saharan African countries including Mozambique, Niger, Nigeria, Ghana, Kenya, and Malawi. It identifies numerous polymorphic sites and reveals moderate genetic variation within the IgA1 gene, underscoring the complex population structures of S. pneumoniae across African countries such as Malawi, Kenya and Ghana. In comparison, higher genetic variation was observed in Asian isolates. Phylogenetic analysis indicated distinct evolutionary lineages, suggesting potential gene flow and shared evolutionary pressures. Mutations identified in key amino acids namely; lysine and asparagine of IgA1 protease may influence the enzyme’s stability, catalytic activity and interaction with host immune components as shown by molecular docking analysis. This could potentially impact the pathogen’s virulence and the effectiveness of existing vaccines and therapeutics. The findings highlight the importance of continuous genomic surveillance and the integration of genomic and proteomic data to inform the development of targeted interventions. This research provides a foundation for future therapeutic and vaccine development efforts aimed at mitigating the impact of S. pneumoniae on global public health. IgA1 gene in S. pneumoniae of African serotype 1 showed moderate genetic variability in isolates of Sub-Saharan Africa. IgA1 gene showed distinct evolutionary lineages of isolates of Sub-Saharan Africa suggesting uniqueness of each population. Mutations in IgA1 protease may potentially enhance pathogen virulence and affect current vaccine effectiveness.