Abstract

Group B streptococcus (GBS, Streptococcus agalactiae) is a leading cause of meningitis and sepsis in newborns and an etiological agent of meningitis, endocarditis, osteoarticular and soft tissue infections in adults. GBS isolates are routinely clustered in serotypes and in genotypes. At present one GBS sequence type (i.e. ST17) is considered to be closely associated with bacterial invasiveness and novel proteomic biomarkers could make a valuable contribution to currently available GBS typing data. For that purpose we analyzed the protein profiles of 170 genotyped GBS isolates by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI). Univariate statistical analysis of the SELDI profiles identified four protein biomarkers significantly discriminating ST17 isolates from those of the other sequence types. Two of these biomarkers (MW of 7878 Da and 12200 Da) were overexpressed and the other two (MW of 6258 Da and 10463 Da) were underexpressed in ST17. The four proteins were isolated by mass spectrometry-assisted purification and their tryptic peptides analyzed by LC-MS/MS. They were thereby identified as the small subunit of exodeoxyribonuclease VII, the 50S ribosomal protein L7/L12, a CsbD-like protein and thioredoxin, respectively. In conclusion, we identified four candidate biomarkers of ST17 by SELDI for high-throughput screening. These markers may serve as a basis for further studies on the pathophysiology of GBS infection, and for the development of novel vaccines.

Highlights

  • Group B streptococcus (GBS), referred to as Streptococcus agalactiae, is the leading cause of infection in newborns [1]

  • The biomarker p7878, present in all except one of the 46 isolates belonging to sequence type 17 (ST17), is found in all isolates of multilocus sequence typing (MLST) group A and the closely related MLST group B

  • We studied a large selection of 170 representative isolates of S. agalactiae to identify proteomic biomarkers that could better characterize their MLST genotypes [14]

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Summary

Introduction

Group B streptococcus (GBS), referred to as Streptococcus agalactiae, is the leading cause of infection in newborns [1]. This bacterial pathogen is a causative agent of invasive infections in adults such as meningitis, endocarditis, and soft tissue and osteoarticular infections [2,3,4]. The GBS isolates have been classified into ten different serotypes according to their capsule polysaccharides [5,6] One of these serotypes, serotype III, is generally associated with late-onset neonatal disease [7], serotyping has turned out to be insufficient to distinguish isolates involved in other clinical outcomes of GBS infection. MLVA [13,14] and other genotyping studies [15,16] have shown that isolates belonging to one particular genotype cluster, the sequence type 17 (ST17), are associated with more invasive behavior, especially in the late-onset GBS disease in newborns

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