Relationship of
            <i>plcR</i>
            -Regulated Factors to
            <i>Bacillus</i>
            Endophthalmitis Virulence

Callegan, Michelle C.; Kane, Scott T.; Cochran, Daniel C.; Gilmore, Michael S.; Gominet, Myriam; Lereclus, Didier

doi:10.1128/iai.71.6.3116-3124.2003

Cited by 86 publications

(115 citation statements)

References 23 publications

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“…For B. cereus and B. thuringiensis, the quorum sensing transcriptional regulator plcR controls the expression of many extracellular virulence factors (Agaisse, et al, 1999). In an experimental rabbit model of endophthalmitis, B. cereus and B. thuringiensis were significantly less virulent when plcR was nonfunctional (Callegan, et al, 2003 Conf., 2005). In terms of individual toxins, those tested to date (hemolysin BL, phosphatidylinositol-specific phospholipase C, and phosphatidylcholine-specific phospholipase C) contributed little to the overall pathogenesis of experimental B. cereus endophthalmitis (Callegan, et al, 1999b(Callegan, et al, ,2002a.…”

Section: Bacillusmentioning

confidence: 99%

Bacterial endophthalmitis: Therapeutic challenges and host–pathogen interactions

Callegan

Gilmore

Gregory

et al. 2007

Progress in Retinal and Eye Research

156

153

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Endophthalmitis is an infection of the posterior segment of the eye that frequently results in loss of vision. This devastating result occurs despite prompt and often aggressive therapeutic and surgical intervention. Over the past decade, research has centered on determining the bacterial and host factors involved in this potentially blinding disease. The initial focus on the bacterial factors responsible for intraocular virulence has recently expanded into analysis the inflammatory response to infection, including the molecular and cellular interactions between the pathogen and host. This review discusses the epidemiology and therapeutic challenges posed by endophthalmitis, as well as recent findings from the analysis of interactions between the host and pathogen. Based on these findings, a model for the pathogenesis of endophthalmitis is presented. A more comprehensive understanding of the molecular and cellular interactions taking place between pathogen and host during endophthalmitis will expose possible therapeutic targets designed to arrest the infection and prevent vision loss.

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Section: Bacillusmentioning

confidence: 99%

Bacterial endophthalmitis: Therapeutic challenges and host–pathogen interactions

Callegan

Gilmore

Gregory

et al. 2007

Progress in Retinal and Eye Research

156

153

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“…It was shown to be a pleiotropic regulator controlling the expression of 45 genes including virulence factors, such as enterotoxins, cytotoxins, and hemolysins (5). Virulence of a plcR-deficient mutant is abolished in various animal models of infection (11,12). PlcR activates the transcription of its target genes by binding to a consensus sequence defined as wTATGnAwwwwTnCATAw (5,13).…”

mentioning

confidence: 99%

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

Grenha

Slamti

Nicaise

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The quorum-sensing regulator PlcR is the master regulator of most known virulence factors in Bacillus cereus. It is a helix-turn-helix (HTH)-type transcription factor activated upon binding of its cognate signaling peptide PapR on a tetratricopeptide repeat-type regulatory domain. The structural and functional properties of PlcR have defined a new family of sensor regulators, called the RNPP family (for Rap, NprR, PrgX, and PlcR), in Gram-positive bacteria. To fully understand the activation mechanism of PlcR, we took a closer look at the conformation changes induced upon binding of PapR and of its target DNA, known as PlcR-box. For that purpose we have determined the structures of the apoform of PlcR (Apo PlcR) and of the ternary complex of PlcR with PapR and the PlcR-box from the plcA promoter. Comparison of the apoform of PlcR with the previously published structure of the PlcR-PapR binary complex shows how a small conformational change induced in the C-terminal region of the tetratricopeptide repeat (TPR) domain upon peptide binding propagates via the linker helix to the N-terminal HTH DNA-binding domain. Further comparison with the PlcR-PapR-DNA ternary complex shows how the activation of the PlcR dimer allows the linker helix to undergo a drastic conformational change and subsequent proper positioning of the HTH domains in the major groove of the two half sites of the pseudopalindromic PlcR-box. Together with random mutagenesis experiments and interaction measurements using peptides from distinct pherogroups, this structural analysis allows us to propose a molecular mechanism for this functional switch

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“…When the bacteria enter the sporulation process, plcR transcription, and consequently PlcR-regulated gene expression, is repressed by the key sporulation regulator Spo0A (40). Deletion of plcR reduces, but does not abolish, the virulence of the bacteria in insects and mice, and during endophthalmitis in rabbits (6,52), suggesting that other factors may be involved. Moreover, B. anthracis does not express plcR, and introduction of a functional copy does not increase its virulence in a murine model (44).…”

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confidence: 99%

The InhA Metalloproteases ofBacillus cereusContribute Concomitantly to Virulence

et al. 2010

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The virulence of Bacillus cereus requires that bacteria have the capacity to colonize their host, degrade specific tissues, and circumvent the host immune system. To study this aspect of pathogenesis, we focused on three metalloproteases, InhA1, InhA2, and InhA3, which share more than 66% identity. The expression of these metalloprotease genes was assessed by transcriptional fusions with a lacZ reporter gene. The expression profiles suggest a complementary time course of InhA production. Indeed, the genes are simultaneously expressed but are oppositely controlled during stationary phase. We constructed single and multiple inhA mutants and assessed the bacterial locations of the proteins as well as their individual or additive roles in macrophage escape and toxicity, antibacterial-peptide cleavage, and virulence. InhA1, a major component of the spore exosporium, is the only InhA metalloprotease involved in bacterial escape from macrophages. A mutant lacking inhA1, inhA2, and inhA3 shows a strong decrease in the level of virulence for insects. Taken together, these results show that the InhA metalloproteases of B. cereus are important virulence factors that may allow the bacteria to counteract the host immune system.

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Relationship of plcR -Regulated Factors to Bacillus Endophthalmitis Virulence

Cited by 86 publications

References 23 publications

Bacterial endophthalmitis: Therapeutic challenges and host–pathogen interactions

Bacterial endophthalmitis: Therapeutic challenges and host–pathogen interactions

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

The InhA Metalloproteases ofBacillus cereusContribute Concomitantly to Virulence

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