Abstract
Group B Streptococcus (GBS) is a leading cause of bacterial sepsis and meningitis in newborns. GBS possesses a protein with homology to the pneumococcal virulence factor, NanA, which has neuraminidase (sialidase) activity and promotes blood-brain barrier penetration. However, phylogenetic sequence and enzymatic analyses indicate the GBS NanA ortholog has lost sialidase function – and for this distinction we designate the gene and encoded protein nonA/NonA. Here we analyze NonA function in GBS pathogenesis, and through heterologous expression of active pneumococcal NanA in GBS, potential costs of maintaining sialidase function. GBS wild-type and ΔnonA strains lack sialidase activity, but forced expression of pneumococcal NanA in GBS induced degradation of the terminal sialic acid on its exopolysaccharide capsule. Deletion of nonA did not change GBS-whole blood survival or brain microvascular cell invasion. However, forced expression of pneumococcal NanA in GBS removed terminal sialic acid residues from the bacterial capsule, restricting bacterial proliferation in human blood and in vivo upon mouse infection. GBS expressing pneumococcal NanA had increased invasion of human brain microvascular endothelial cells. Thus, we hypothesize that nonA lost enzyme activity allowing the preservation of an effective survival factor, the sialylated exopolysaccharide capsule.
Highlights
Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that is a leading cause of sepsis, pneumonia, and meningitis during neonatal period and up to the first 90 days of life[1,2]
E. rhusiopathiae and C. perfringens are known to produce active sialidases[18,19,20]. Both trees indicate that the nanA ortholog genes of S. mitis and S. pseudopneumoniae diverged from each other, having shared a common ancestor
The phylogenetic analysis revealed that the GBS nonA represents a single lineage in a cluster otherwise composed of S. iniae, which is a pathogen of fish and occasional nosocomial infections in humans[21]
Summary
Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that is a leading cause of sepsis, pneumonia, and meningitis during neonatal period and up to the first 90 days of life[1,2]. In contrast to GBS, no S. pneumoniae strains express sialic acid in its capsular polysaccharide. Our bioinformatics analysis suggested that, unlike pneumococcal NanA, the GBS orthologue has lost the LamG domain and cell wall-anchoring motif, and that there was a nonsense mutation in this gene in some GBS strains. In contrast to earlier published findings with pneumococcal NanA mutants[13,14,16], targeted deletion of the nonA gene in GBS did not alter resistance to human whole blood killing, brain microvascular endothelial cell invasion, or animal virulence. Forced expression of active pneumococcal NanA in the GBS ΔnonA mutant removed terminal sialic acid from the GBS polysaccharide capsule, reducing GBS survival in whole blood, while promoting GBS invasion of brain microvascular endothelial cells. Our results strongly suggest that the loss of function as a sialidase in GBS NonA in contemporary GBS strains allowed the organism to preserve the selective advantage of sialylated capsule
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
