In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection

Sadaka, Ama; Palmer, Kelli L.; Suzuki, Takashi; Gilmore, Michael S.

doi:10.1371/journal.pone.0110872

Cited by 8 publications

(8 citation statements)

References 45 publications

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“…Another biofilm-related tissue infection that afflicts the eye is endophthalmitis. In 2014, Sadaka et al (2014) developed a mouse model in which biofilm-related anterior chamber infections characteristic of endophthalmitis could be studied. Interested in showing a link between the branched-chain amino acid responsive transcription regulator CodY and endophthalmitis, the study looked to investigate the impact of CodY deletion on S. aureus virulence within a murine anterior chamber model.…”

Section: Recently Developed In Vivo Biofilm Modelsmentioning

confidence: 99%

“…Interested in showing a link between the branched-chain amino acid responsive transcription regulator CodY and endophthalmitis, the study looked to investigate the impact of CodY deletion on S. aureus virulence within a murine anterior chamber model. Briefly, the anterior chamber of the right eye was inoculated with S. aureus using a 35G needle on a NanoFil syringe just anterior to the limbus without Recent in vivo biofilm models for tissue-related infection Endophthalmitis (Sadaka et al, 2014) The anterior chamber of the right eye is inoculated with S. aureus using a 35-G needle on a NanoFil syringe just anterior to the limbus without touching the iris.…”

Section: Recently Developed In Vivo Biofilm Modelsmentioning

confidence: 99%

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Mimicking biofilm formation and development: Recent progress in in vitro and in vivo biofilm models

et al. 2021

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Biofilm formation in living organisms is associated to tissue and implant infections, and it has also been linked to the contribution of antibiotic resistance. Thus, understanding biofilm development and being able to mimic such processes is vital for the successful development of antibiofilm treatments and therapies. Several decades of research have contributed to building the foundation for developing in vitro and in vivo biofilm models. However, no such thing as an ''all fit'' in vitro or in vivo biofilm models is currently available. In this review, in addition to presenting an updated overview of biofilm formation, we critically revise recent approaches for the improvement of in vitro and in vivo biofilm models.

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Section: Recently Developed In Vivo Biofilm Modelsmentioning

confidence: 99%

Section: Recently Developed In Vivo Biofilm Modelsmentioning

confidence: 99%

Mimicking biofilm formation and development: Recent progress in in vitro and in vivo biofilm models

et al. 2021

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“…The knockout strain lacking both SarA and Agr lost about three-fourths of its virulence [ 130 , 131 ]. In addition to the analysis of SarA and Agr, studies of another toxin regulator known as CodY were performed [ 132 ]. The repression of virulence genes by CodY is controlled by branched chain amino acids in the environment; the presence of these amino acids permit repression of virulence genes by CodY.…”

Section: Endophthalmitismentioning

confidence: 99%

The Pathogenesis of Staphylococcus aureus Eye Infections

O’Callaghan

2018

Pathogens

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Staphylococcus aureus is a major pathogen of the eye able to infect the tear duct, eyelid, conjunctiva, cornea, anterior and posterior chambers, and the vitreous chamber. Of these infections, those involving the cornea (keratitis) or the inner chambers of the eye (endophthalmitis) are the most threatening because of their potential to cause a loss in visual acuity or even blindness. Each of these ocular sites is protected by the constitutive expression of a variety of antimicrobial factors and these defenses are augmented by a protective host response to the organism. Such infections often involve a predisposing factor that weakens the defenses, such as the use of contact lenses prior to the development of bacterial keratitis or, for endophthalmitis, the trauma caused by cataract surgery or intravitreal injection. The structural carbohydrates of the bacterial surface induce an inflammatory response able to reduce the bacterial load, but contribute to the tissue damage. A variety of bacterial secreted proteins including alpha-toxin, beta-toxin, gamma-toxin, Panton-Valentine leukocidin and other two-component leukocidins mediate tissue damage and contribute to the induction of the inflammatory response. Quantitative animal models of keratitis and endophthalmitis have provided insights into the S. aureus virulence and host factors active in limiting such infections.

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“…CodY's role in controlling virulence during infection has been firmly established in multiple Gram-positive pathogens, including S. aureus, Listeria monocytogenes, and Bacillus anthracis (51)(52)(53)(54)(55)(56)(57)(58). Surprisingly, a comparison of the set of genes differentially regulated by S. aureus CodY in vitro with the gene targets identified using an in vitro DNA:CodY pulldown experiment revealed that fewer than half of the virulence genes under CodY control are directly regulated (36).…”

Section: Discussionmentioning

confidence: 99%

Nutritional Regulation of the Sae Two-Component System by CodY in Staphylococcus aureus

et al. 2018

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subverts innate defenses during infection in part by killing host immune cells to exacerbate disease. This human pathogen intercepts host cues and activates a transcriptional response via the exoprotein expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors critical for pathogenesis. We recently showed that the transcriptional repressor CodY adjusts nuclease () gene expression via SaeR/S, but the mechanism remained unknown. Here, we identified two CodY binding motifs upstream of the P1 promoter, which suggested direct regulation by this global regulator. We show that CodY shares a binding site with the positive activator SaeR and that alleviating direct CodY repression at this site is sufficient to abrogate stochastic expression, suggesting that CodY represses expression by blocking SaeR binding. Epistasis experiments support a model that CodY also controls indirectly through Agr and Rot-mediated repression of the P1 promoter. We also demonstrate that CodY repression of restrains production of secreted cytotoxins that kill human neutrophils. We conclude that CodY plays a previously unrecognized role in controlling virulence gene expression via SaeR/S and suggest a mechanism by which CodY acts as a master regulator of pathogenesis by tying nutrient availability to virulence gene expression. Bacterial mechanisms that mediate the switch from a commensal to pathogenic lifestyle are among the biggest unanswered questions in infectious disease research. Since the expression of most virulence genes is often correlated with nutrient depletion, this implies that virulence is a response to the lack of nourishment in host tissues and that pathogens like produce virulence factors in order to gain access to nutrients in the host. Here, we show that specific nutrient depletion signals appear to be funneled to the SaeR/S system through the global regulator CodY. Our findings reveal a strategy by which delays the production of immune evasion and immune-cell-killing proteins until key nutrients are depleted.

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In Vitro and In Vivo Models of Staphylococcus aureus Endophthalmitis Implicate Specific Nutrients in Ocular Infection

Cited by 8 publications

References 45 publications

Mimicking biofilm formation and development: Recent progress in in vitro and in vivo biofilm models

Mimicking biofilm formation and development: Recent progress in in vitro and in vivo biofilm models

The Pathogenesis of Staphylococcus aureus Eye Infections

Nutritional Regulation of the Sae Two-Component System by CodY in Staphylococcus aureus

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