Abstract

Streptococcus pneumoniae is among the top causes of bacterial endophthalmitis, an infectious disease of the intraocular fluids. The mechanisms by which S. pneumoniae grows and thrives in the intraocular cavity are not well understood. We used a bacterial genome-wide assessment tool (transposon insertion site sequencing) to determine genes essential for S. pneumoniae growth in vitreous humor. The results indicated that an ascorbic acid (AA) transport system subunit was important for growth. We created an isogenic gene deletion mutant of the AA transcriptional activator, ulaR2, in 2 strains of S. pneumoniae. Growth curve analysis indicated that ulaR2 deletion caused attenuated growth in vitro for both strains. However, in vivo vitreous humor infection in rabbits with either strain determined that ulaR2 was necessary for growth in one strain but not the other. These results demonstrate that ulaR2 may be important for fitness during S. pneumoniae endophthalmitis depending on the background of the strain.

Highlights

  • Streptococcal species are among the top causes of bacterial endophthalmitis, an infectious disease of the aqueous and/or vitreous humors of the eye [1,2,3]

  • The current knowledge of S. pneumoniae endophthalmitis includes demonstration that at least two bacterial virulence factors are important for disease

  • Comparison of sequencing reads between the D39 transposon mutant library grown in Todd Hewitt broth containing yeast extract (THY) and that grown in rabbit vitreous humor indicated 6 specific S. pneumoniae genes required for growth in vitreous humor (Table 2)

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Summary

Introduction

Streptococcal species are among the top causes of bacterial endophthalmitis, an infectious disease of the aqueous and/or vitreous humors of the eye [1,2,3]. The cholesterol-dependent cytolysin of S. pneumoniae, pneumolysin, was shown to be necessary for ocular disease severity in animal models of endophthalmitis [8,9,10]. Blocking pneumolysin by immunization had no effect on bacterial recovery from the vitreous humor [10]. The outer polysaccharide capsule of S. pneumoniae, which forms the basis of serotyping encapsulated strains and is classically associated with immune evasion, was determined to be essential for virulence during endophthalmitis [11]. As well as bacterial recovery from the vitreous humor, were significantly lower in rabbits infected with an isogenic capsule-deficient strain of S. pneumoniae compared to the parent strain

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