Variable Release of Lipoteichoic Acid From Staphylococcus aureus Bloodstream Isolates Relates to Distinct Clinical Phenotypes, Strain Background, and Antibiotic Exposure.

Marquerita Algorri,Peter Jorth,Annie Wong-Beringer

doi:10.3389/fmicb.2020.609280

Marquerita Algorri, Peter Jorth + Show 1 more

Open Access

https://doi.org/10.3389/fmicb.2020.609280

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Abstract

BackgroundStaphylococcus aureus is a leading cause of bacterial bloodstream infections. The heterogeneity in patient outcomes in S. aureus bacteremia (SAB) can be attributed in part to strain characteristics, which may influence host response to infection. We specifically examined the relationship between lipoteichoic acid (LTA) release from S. aureus and disease phenotype, strain background, and antibiotic exposure.MethodsSeven strains of S. aureus causing different clinical phenotypes of bacteremia and two reference strains (LAC USA 300 and Mu3) were analyzed for LTA release at baseline and following exposure to antibiotics from different pharmacologic classes (vancomycin, ceftaroline, and tedizolid). LTA release was quantified by LTA-specific ELISA. Whole genome sequencing was performed on the clinical strains and analyzed using open-source bioinformatics tools.ResultsLipoteichoic acid release varied by 4-fold amongst the clinical strains and appeared to be related to duration of bacteremia, independent of MLST type. Low LTA releasing strains were isolated from patients who had prolonged duration of bacteremia and died. Antibiotic-mediated differences in LTA release appeared to be associated with MLST type, as ST8 strains released maximal LTA in response to tedizolid while other non-ST8 strains demonstrated high LTA release with vancomycin. Genetic variations related to the LTA biosynthesis pathway were detected in all non-ST8 strains, though ST8 strains showed no variations despite demonstrating differential LTA release.ConclusionOur findings provide the basis for future studies to evaluate the relationship between LTA release-mediated host immune response and clinical outcomes as well as the potential for antibiotic modulation of LTA release as a therapeutic strategy and deserve confirmation with larger number of strains with known clinical phenotypes.

Highlights

Staphylococcus aureus is a leading cause of bloodstream infections and bacterial sepsis associated with significant morbidity and mortality (Naber, 2009; Liu et al, 2011; Mayr et al, 2014)
Release of lipoteichoic acid (LTA) from bacterial cells into the culture supernatant was assessed using ELISA to examine differences in LTAreleasing capabilities between strains that may correlate with clinical phenotypes
We assessed the relationship between strain lineage background and LTA release by comparing the amount of LTA release based on Multilocus sequence typing (MLST) sequence type (ST) (Figure 1B)

Summary

Introduction

Staphylococcus aureus is a leading cause of bloodstream infections and bacterial sepsis associated with significant morbidity and mortality (Naber, 2009; Liu et al, 2011; Mayr et al, 2014). Previous studies have demonstrated notable heterogeneity in clinical presentation and outcomes in patients with S. aureus bloodstream infections (SAB) (Naber, 2009; van Hal et al, 2012). The observed heterogeneity in clinical outcomes can be attributed, in part, to differential expression of virulence factors and resistance mechanisms across S. aureus strains (Minejima et al, 2016; Cyr et al, 2017; Pérez-Montarelo et al, 2018). The heterogeneity in patient outcomes in S. aureus bacteremia (SAB) can be attributed in part to strain characteristics, which may influence host response to infection. We examined the relationship between lipoteichoic acid (LTA) release from S. aureus and disease phenotype, strain background, and antibiotic exposure

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Conclusion