June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Impact of master bacterial virulence regulators on the host response to Staphylococcus aureus keratitis
Author Affiliations & Notes
  • William L Johnson
    Ophthalmology, University of Rochester Medical Center, Rochester, New York, United States
  • Payel Chatterjee
    Yale University School of Medicine, New Haven, Connecticut, United States
  • Michaelle Chojnacki
    Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States
  • Collynn Woeller
    Ophthalmology, University of Rochester Medical Center, Rochester, New York, United States
  • Rachel Wozniak
    Ophthalmology, University of Rochester Medical Center, Rochester, New York, United States
  • Footnotes
    Commercial Relationships   William Johnson, None; Payel Chatterjee, None; Michaelle Chojnacki, None; Collynn Woeller, None; Rachel Wozniak, None
  • Footnotes
    Support  NIH K08 EY029012-02, Research to Prevent Blindess Career Development Award
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1964. doi:
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      William L Johnson, Payel Chatterjee, Michaelle Chojnacki, Collynn Woeller, Rachel Wozniak; Impact of master bacterial virulence regulators on the host response to Staphylococcus aureus keratitis. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1964.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Bacterial keratitis (BK) is a major cause of blindness worldwide. Staphylococcus aureus is the predominant organism implicated in BK and causes considerable ocular tissue damage largely due to the ability to significantly modulate the host immune response via secreted virulence factors. In S. aureus, Agr and Sae are two important virulence regulators, yet their role in BK is yet unknown. This study investigated the role of Agr and Sae in host cytokine production in a murine model of BK.

Methods : S. aureus isolates USA300 (WT), USA300ΔsaePQRS, and USA300Δagr, were used to inoculate the corneas of BLALB/c mice. At 24 and 48 hours, eyes were harvested, homogenized and evaluated for the abundance of a panel of cytokines including interleukin 6 (IL6), interleukin 12 (IL12), and tumor necrosis factor alpha (TNFα) using standard sandwich ELISA assays. Three biological replicates were assayed for each strain and time point.

Results : IL-6 was significantly elevated in mice infected with S. aureus USA300ΔsaePQRS at 24 h post infection compared to USA300 (WT) or USA300Δagr (ANOVA, P = 0.005; Tukey-Kramer post hoc test, P = 0.021 and P = 0.005, respectively). Production of IL6 at 48 h post infection was not significantly different between the three strains (ANOVA, P = 0.34). No significant differences were detected between strains at 24 or 48 hours for IL12 (ANOVA, P = 0.1753 and P = 0.1951, respectively) or TNFα (ANOVA, P = 0.5440 and P = 0.3663, respectively).

Conclusions : Agr and Sae are well-known virulence factor regulators in S. aureus yet their downstream effectors and resulting host response is not well characterized in BK. Here we demonstrate that Sae significantly impacts IL-6 production in a murine model of BK in the early stages of infection. Targeting bacterial factors that modulate the host immune response may provide a therapeutic approach to treating this blinding disease.

This is a 2021 ARVO Annual Meeting abstract.

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