Journal article
Association of Novel Streptococcus sanguinis Virulence Factors With Pathogenesis in a Native Valve Infective Endocarditis Model
Frontiers in microbiology, Vol.11, pp.10-10
01/31/2020
DOI: 10.3389/fmicb.2020.00010
PMCID: PMC7005726
PMID: 32082276
Abstract
Streptococcus sanguinis
(
S. sanguinis
) is an abundant oral commensal which can cause disseminated human infection if it gains access to the bloodstream. The most important among these diseases is infective endocarditis (IE). While virulence phenotypes of
S. sanguinis
have been correlated to disease severity, genetic factors mediating these phenotypes, and contributing to pathogenesis are largely uncharacterized. In this report, we investigate the roles of 128 genes in virulence-related phenotypes of
S. sanguinis
and characterize the pathogenic potential of two selected mutants in a left-sided, native valve IE rabbit model. Assays determining the ability of our mutant strains to produce a biofilm, bind to and aggregate platelets, and adhere to or invade endothelial cells identified sixteen genes with novel association to these phenotypes. These results suggest the presence of many uncharacterized genes involved in IE pathogenesis which may be relevant for disease progression. Two mutants identified by the above screening process –
SSA_1099
, encoding an RTX-like protein, and
mur2
, encoding a peptidoglycan hydrolase – were subsequently evaluated
in vivo
. Wild type (WT)
S. sanguinis
reliably induced cardiac vegetations, while the
SSA_1099
and
mur2
mutants produced either no vegetation or vegetations of small size. Splenomegaly was reduced in both mutant strains compared to WT, while pathology of other distal organs was indistinguishable. Histopathology analyses suggest the cardiac lesions and vegetations in this model resemble those observed in humans. These data indicate that
SSA_1099
and
mur2
encode virulence factors in
S. sanguinis
which are integral to pathogenesis of IE.
Details
- Title: Subtitle
- Association of Novel Streptococcus sanguinis Virulence Factors With Pathogenesis in a Native Valve Infective Endocarditis Model
- Creators
- Anthony M. Martini - Roy J. and Lucille A. Carver College of MedicineBridget S. Moricz - Roy J. and Lucille A. Carver College of MedicineAllison K. Ripperger - Roy J. and Lucille A. Carver College of MedicinePhuong M. Tran - Roy J. and Lucille A. Carver College of MedicineMolly E. Sharp - Roy J. and Lucille A. Carver College of MedicineAna N. Forsythe - Roy J. and Lucille A. Carver College of MedicineKatarina Kulhankova - Roy J. and Lucille A. Carver College of MedicineWilmara Salgado-Pabón - Roy J. and Lucille A. Carver College of MedicineBradley D. Jones - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in microbiology, Vol.11, pp.10-10
- DOI
- 10.3389/fmicb.2020.00010
- PMID
- 32082276
- PMCID
- PMC7005726
- NLM abbreviation
- Front Microbiol
- ISSN
- 1664-302X
- eISSN
- 1664-302X
- Publisher
- Frontiers Media S.A
- Language
- English
- Date published
- 01/31/2020
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Stead Family Department of Pediatrics
- Record Identifier
- 9984297327202771
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