Commonly used molecular epidemiology markers of Streptococcus agalactiae do not appear to predict virulence

Frank Lin, Vitali Sintchenko, Fanrong Kong, Gwendolyn L. Gilbert, Enrico Coiera

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Aims: Several virulent clones of group B streptococcus GBS are known to be associated with certain serotypes and molecular epidemiological markers. It is unclear, however, whether the clinical significance of GBS can be predicted based solely on such molecular markers. The aim of this study was to test the hypothesis that GBS virulence can be predicted by using the molecular epidemiology markers. Methods: We examined 912 human GBS isolates in which 18 distinct molecular markers including virulence-associated mobile genetic elements, polysaccharide capsule determinants, variants of a surface antigen and invasin, and antibiotic resistance-related genes were characterised using multiplex PCR based reverse line blot assay. All strains were classified in clinically relevant invasive and colonising categories. Relationships between molecular markers and clinical phenotypes were tested using statistical and machine learning analyses. Classifier performance was evaluated by the area under receiver operator characteristic curve AUC. Results: The distribution of serotypes was comparable with those in previous reports Ia, 22.1; III, 34.7; V, 17.7. From single marker analyses, only alp3 which encodes a surface protein antigen, commonly associated with serotype V showed an increased association with invasive diseases OR 2.93, p 0.0003. Molecular serotype MS II OR 10.0, p 0.0007 had a significant association with early-onset neonatal disease when compared with late-onset diseases. Predictive analysis with logistic regression and machine learning classifiers, however, only yielded weak predictive power AUC 0.560.71, stratified 10-fold cross-validation across all the subgroups. Conclusion: While some molecular epidemiological markers are important in defining GBS clusters, a definitive predictive relationship between the molecular markers and clinical outcomes may be lacking.

LanguageEnglish
Pages576-581
Number of pages6
JournalPathology
Volume41
Issue number6
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Streptococcus agalactiae
Molecular Epidemiology
Virulence
Surface Antigens
Area Under Curve
Infant, Newborn, Diseases
Biomarkers
Interspersed Repetitive Sequences
Multiplex Polymerase Chain Reaction
Microbial Drug Resistance
Capsules
Polysaccharides
Membrane Proteins
Clone Cells
Logistic Models
Phenotype
Serogroup
Genes
Machine Learning

Cite this

Lin, Frank ; Sintchenko, Vitali ; Kong, Fanrong ; Gilbert, Gwendolyn L. ; Coiera, Enrico. / Commonly used molecular epidemiology markers of Streptococcus agalactiae do not appear to predict virulence. In: Pathology. 2009 ; Vol. 41, No. 6. pp. 576-581.
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abstract = "Aims: Several virulent clones of group B streptococcus GBS are known to be associated with certain serotypes and molecular epidemiological markers. It is unclear, however, whether the clinical significance of GBS can be predicted based solely on such molecular markers. The aim of this study was to test the hypothesis that GBS virulence can be predicted by using the molecular epidemiology markers. Methods: We examined 912 human GBS isolates in which 18 distinct molecular markers including virulence-associated mobile genetic elements, polysaccharide capsule determinants, variants of a surface antigen and invasin, and antibiotic resistance-related genes were characterised using multiplex PCR based reverse line blot assay. All strains were classified in clinically relevant invasive and colonising categories. Relationships between molecular markers and clinical phenotypes were tested using statistical and machine learning analyses. Classifier performance was evaluated by the area under receiver operator characteristic curve AUC. Results: The distribution of serotypes was comparable with those in previous reports Ia, 22.1; III, 34.7; V, 17.7. From single marker analyses, only alp3 which encodes a surface protein antigen, commonly associated with serotype V showed an increased association with invasive diseases OR 2.93, p 0.0003. Molecular serotype MS II OR 10.0, p 0.0007 had a significant association with early-onset neonatal disease when compared with late-onset diseases. Predictive analysis with logistic regression and machine learning classifiers, however, only yielded weak predictive power AUC 0.560.71, stratified 10-fold cross-validation across all the subgroups. Conclusion: While some molecular epidemiological markers are important in defining GBS clusters, a definitive predictive relationship between the molecular markers and clinical outcomes may be lacking.",
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Commonly used molecular epidemiology markers of Streptococcus agalactiae do not appear to predict virulence. / Lin, Frank; Sintchenko, Vitali; Kong, Fanrong; Gilbert, Gwendolyn L.; Coiera, Enrico.

In: Pathology, Vol. 41, No. 6, 2009, p. 576-581.

Research output: Contribution to journalArticleResearchpeer-review

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