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Infect Immun. 2015 Nov 9;84(1):307-19. doi: 10.1128/IAI.00938-15. Print 2016 Jan.

Discovery and Characterization of Human-Urine Utilization by Asymptomatic-Bacteriuria-Causing Streptococcus agalactiae.

Author information

1
School of Medical Sciences, Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, QLD, Australia.
2
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
3
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
4
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
5
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
6
Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, Australia.
7
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
8
Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
9
School of Medical Sciences, Menzies Health Institute Queensland, Griffith University, Gold Coast Campus, QLD, Australia Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA g.ulett@griffith.edu.au.

Abstract

Streptococcus agalactiae causes both symptomatic cystitis and asymptomatic bacteriuria (ABU); however, growth characteristics of S. agalactiae in human urine have not previously been reported. Here, we describe a phenotype of robust growth in human urine observed in ABU-causing S. agalactiae (ABSA) that was not seen among uropathogenic S. agalactiae (UPSA) strains isolated from patients with acute cystitis. In direct competition assays using pooled human urine inoculated with equal numbers of a prototype ABSA strain, designated ABSA 1014, and any one of several UPSA strains, measurement of the percentage of each strain recovered over time showed a markedly superior fitness of ABSA 1014 for urine growth. Comparative phenotype profiling of ABSA 1014 and UPSA strain 807, isolated from a patient with acute cystitis, using metabolic arrays of >2,500 substrates and conditions revealed unique and specific l-malic acid catabolism in ABSA 1014 that was absent in UPSA 807. Whole-genome sequencing also revealed divergence in malic enzyme-encoding genes between the strains predicted to impact the activity of the malate metabolic pathway. Comparative growth assays in urine comparing wild-type ABSA and gene-deficient mutants that were functionally inactivated for the malic enzyme metabolic pathway by targeted disruption of the maeE or maeK gene in ABSA demonstrated attenuated growth of the mutants in normal human urine as well as synthetic human urine containing malic acid. We conclude that some S. agalactiae strains can grow in human urine, and this relates in part to malic acid metabolism, which may affect the persistence or progression of S. agalactiae ABU.

PMID:
26553467
PMCID:
PMC4694007
DOI:
10.1128/IAI.00938-15
[Indexed for MEDLINE]
Free PMC Article

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