Bacillus S-Layer-Mediated Innate Interactions During Endophthalmitis

Mursalin, Huzzatul; Coburn, Phillip S.; Livingston, Erin; Miller, Frederick C.; Astley, Roger; Flores-Mireles, Ana L.; Callegan, Michelle C.

doi:10.3389/fimmu.2020.00215

Cited by 23 publications

(41 citation statements)

References 140 publications

(245 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism for this effect was linked to activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and subsequent inflammatory mediator production from Muller cells [17]. Further investigation revealed that SlpA activated both TLR2 and TLR4 in vitro, and that administration of TLR2/4 inhibitors attenuated the severity of infection in our mouse model (18,24). These results…”

Section: Discussionsupporting

confidence: 53%

“…At 4 hours postinfection with a CerO-deficient B. cereus strain, TLR4dependent inflammatory mediators were significantly downregulated [33]. TLR4 contributed to the inflammatory response to B. cereus [22], and was activated by purified B. cereus SlpA protein [18]. In addition to direct cellular cytotoxicity, CerO as a CDC might interact with and/or activate TLR4 [34][35][36][37], inciting inflammation during B. cereus endophthalmitis.…”

Section: Discussionmentioning

confidence: 99%

“…SlpA, has been shown to play a key role in activation of both TLR-2 and -4 and in the severity of infection in a mouse model of Bacillus endophthalmitis [17,18,24]. The mean RPKM of slpA was 25 in vivo, and 36 after growth in BHI (Fig.…”

Section: Expression Of Surface Layer Protein (Slpa) In Vivo the Bacimentioning

confidence: 94%

“…Superoxide dismutase expression levels in vivo were also measured, as our previous data suggested an important role for this factor [20]. Finally, the expression of the surface layer protein gene (slpA) was evaluated as this protein is an important contributor to activation of TLR-2 and -4 receptors and initiation of the inflammatory response [18,24]. Principal component analysis of the RPKM values for each of these mRNAs isolated from B. cereus after 8 hours of growth in BHI or 8 hours after intravitreal injection was performed.…”

Section: Growth Of B Cereus In Bhi and In Vivomentioning

confidence: 99%

“…In the same model, a mutant strain of Bacillus deficient in the S-layer protein, SlpA, was less virulent relative to the wild type, parental strain [17]. Moreover, Bacillus SlpA stimulated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in human retinal Muller cells in vitro, interfered with phagocytosis by neutrophils and retinal cells, and served as an adhesin to retinal cells [18]. Bacillus flagella contribute to the intraocular virulence of B. cereus by facilitating migration throughout the eye [12].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

TheBacillusVirulome in Endophthalmitis

Coburn

Miller

Enty

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

AbstractBacillus cereus is recognized as a causative agent of gastrointestinal syndromes, but can also cause a devastating form of intraocular infection known as endophthalmitis. We have previously reported that the PlcR/PapR master virulence factor regulator system regulates intraocular virulence, and that the S-layer protein (SlpA) contributes to the severity of B. cereus endophthalmitis. To begin to better understand the role of other B. cereus virulence genes in endophthalmitis, expression levels of a subset of factors was measured at the midpoint of disease progression in a murine model of experimental endophthalmitis by RNA-Seq. Several cytolytic toxins were expressed at significantly higher levels in vivo than in BHI. The virulence regulators codY, gntR, and nprR were also expressed in vivo. However, at this timepoint, plcR/papR was not detectable, we previously reported that a B. cereus mutant deficient in PlcR was attenuated in the eye. The motility-related genes fla, fliF, and motB, and the chemotaxis-related gene cheA were detected during infection. We have shown previously that motility and chemotaxis phenotypes are important in B. cereus endophthalmitis. The sodA2 variant of manganese superoxide dismutase was the most highly expression gene in vivo, suggesting that this gene is criticial for intraocular survival, potentially through inhibition of neutrophil activity. Expression of the surface layer protein gene, slpA, an activator of Toll-like receptors (TLR) −2 and −4, and a potent contributor to intraocular inflammation and disease severvity, was also detected during infection, albeit at low levels. In summary, genes expressed in a mouse model of Bacillus endophthalmitis might prove to play crucial roles in the unique virulence of B. cereus endophthalmitis, and serve as candidates for novel therapies designed attenuate the severity of this often blinding infection.Impact statementB. cereus causes a potent and rapid infection of the eye that usually results in blindness or enucleation, even with the utilization of current treatment modalities. This necessitates the development of new treatment modalities based on new targets. To begin to better define those B. cereus factors with roles in intraocular infection, we analyzed the expression of genes with both known and hypothesized roles in intraocular infection at the midpoint of infection using a murine model of Bacillus endophthalmitis. Potentially targetable candidate genes were demonstrated to be expressed in vivo, which suggests that these genes might contribute to the unique virulence of B. cereus endophthalmitis. Importantly, our results begin to define the virulome of B. cereus in intraocular infections and identify previously uncharacterized factors with potential roles in the severity and outcome of Bacillus endophthalmitis.