The Bacillus virulome in endophthalmitis

Abstract

Bacillus 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 better understand the role of other B. cereus virulence genes in endophthalmitis, expression of a subset of factors was measured at the midpoint of disease progression in a murine model of 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, although 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 expressed gene in vivo. Expression of the surface layer protein gene, slpA, an activator of Toll-like receptors (TLR)−2 and −4, was also detected during infection, albeit at low levels. Genes expressed in a mouse model of Bacillus endophthalmitis might play crucial roles in the unique virulence of B. cereus endophthalmitis, and serve as candidates for novel therapies designed to attenuate the severity of this often blinding infection.

An Investigation of Quorum Sensing Inhibitors against Bacillus cereus in The Endophytic Fungus Pithomyces sacchari of the Laurencia sp.

“…Upon the addition of demethylincisterol A3, both the swimming ability and the biofilm production of B. cereus decreased. Genes associated with flagella or mobility, including rpoN, codY, and sinR [38,40], showed significant downregulation after demethylincisterol A3 treatment.…”

Ocular Bacterial Infections: A Ten-Year Survey and Review of Causative Organisms Based on the Oklahoma Experience

“…In addition to its motility, B. cereus possesses adhesive pili [ 25 ] and produces numerous toxins and enzymes which are under the control of the quorum-sensing regulator PlcR [ 25 ]. Bacillus toxins produced in mouse eyes during experimental endophthalmitis include hemolysin BL, nonhemolytic enterotoxin, cereolysin O, and enterotoxins A, C, and FM [ 26 ]. Bacillus rapidly replicates in the ocular environment during an active infection [ 25 ].…”

Virulence-related genotypic differences among Bacillus cereus ocular and gastrointestinal isolates and the relationship to endophthalmitis pathogenesis

“…Endophthalmitis is an intraocular infection that poses a significant threat to vision. It can occur after ocular surgery (referred to as postoperative endophthalmitis or POE), following a traumatic penetrating injury to the globe (known as posttraumatic endophthalmitis or PTE), or as a result of microorganisms crossing the blood retinal barrier following hematogenous spread from another infection site in the body (referred to as endogenous endophthalmitis or EE) (Goldberg et al, 1991;Callegan et al, 1999a;Callegan et al, 2007;Lemley and Han, 2007;Coburn and Callegan, 2012;Durand, 2013;Jackson et al, 2014;Astley et al, 2016;Miller et al, 2019). Posttraumatic endophthalmitis (PTE) occurs in 3-17% of cases involving open globe injuries, and constitutes approximately 25%-30% of all cases of exogenous endophthalmitis (Bhagat et al, 2011).…”

“…Bc endophthalmitis is particularly difficult to treat due to the rapid progression of the infection (Miller et al, 2008;Dave et al, 2018). The significant damage to the eye and poor visual outcomes during Bc endophthalmitis likely results from a combination of mechanisms involving bacterial virulence-related factor production and host immune response to these factors (Callegan et al, 1999a;Callegan et al, 2007;Coburn and Callegan, 2012;Durand, 2013;Jackson et al, 2014;Astley et al, 2016;Miller et al, 2019). The importance of Bc virulence-related factors was evident in the observation that the absence of a subset of these factors, controlled by the PlcR/PapR transcriptional regulatory system, resulted in a marked reduction in the virulence of endophthalmitis (Callegan et al, 2003).…”