A comparison of the early inflammatory effects of an agr-/sar- versus a wild type strain of Staphylococcus aureus in a rat model of endophthalmitis

Giese, Michael J.; Berliner, Judith A.; Riesner, Alissa; Wagar, Elizabeth A.; Mondino, Bartly J.

doi:10.1076/ceyr.18.3.177.5370

Cited by 23 publications

(23 citation statements)

References 11 publications

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“…Furthermore, Cheung et al were unable to demonstrate significantly attenuated virulence for an agr mutant in a rabbit model of endocarditis, although a sar agr double mutant was diminished in both infectivity and intravegetation bacterial densities (2). Additional studies have found that although agr mutants are somewhat attenuated in virulence, they remain clearly capable of causing infection in a rabbit model of osteomyelitis (8) and a rat model of endophthalmitis (7). These studies, combined with the data presented here, suggest a much more complicated picture of staphylococcal virulence than that modeled with agr as a global regulator of virulence factors.…”

Section: Discussionmentioning

confidence: 99%

Repression of the Staphylococcus aureus Accessory Gene Regulator in Serum and In Vivo

et al. 2002

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Subgenomic DNA microarrays were employed to evaluate the expression of the accessory gene regulator (agr locus) as well as multiple virulence-associated genes in Staphylococcus aureus. Gene expression was examined during growth of S. aureus in vitro in standard laboratory medium and rabbit serum and in vivo in subcutaneous chambers implanted in either nonimmune rabbits or rabbits immunized with staphylococcal enterotoxin B. Expression of RNAIII, the effector molecule of the agr locus, was dramatically repressed in serum and in vivo, despite the increased expression of secreted virulence factors sufficient to cause toxic shock syndrome (TSS) in the animals. Statistical analysis and clustering of virulence genes based on their expression profiles in the various experimental conditions demonstrated no positive correlation between the expression of agr and any staphylococcal virulence factors examined. Disruption of the agr locus had only a minimal effect on the expression in vivo of the virulence factors examined. An effect of immunization on the expression of agr and virulence factors was also observed. These results suggest that agr activation is not necessary for development of staphylococcal TSS and that regulatory circuits responding to the in vivo environment override agr activity.A leading cause of nosocomial infections worldwide, Staphylococcus aureus is the etiologic agent of numerous diseases, ranging from relatively benign skin infections to life-threatening illnesses, such as toxic shock syndrome (TSS), septicemia, and osteomyelitis (reviewed in reference 25). Its ability to cause this range of disease is due, in part, to the expression of a wide array of secreted and cell surface-associated virulence factors. The expression of most of these virulence factors has been described as being regulated by the quorum-dependent accessory gene regulator (agr locus). The present model of agr activity and its effect on virulence factor expression is well reviewed elsewhere (15,19). Briefly, the agr locus expresses two primary, divergent transcripts. RNAII (agrBDCA) encodes a two-component system (AgrA-AgrC), recognizing the agrDencoded secreted autoinducing octapeptide (AIP), and AgrB, which is thought to act in the posttranslational processing and secretion of the AIP. The second transcript, RNAIII, acts as the effector molecule of the agr locus. A third, short transcript, RNAI, has been described as encoding AgrA. Upon accumulation in the growth medium of sufficient quantities of the AIP, usually during the transition from the exponential to the stationary phase of growth, signaling via AgrA-AgrC acts to increase transcription of both RNAII and RNAIII. In vitro, this results in the increased expression of secreted virulence factors, including the pyrogenic toxin superantigens and hemolysins, and the repression of numerous surface-associated virulence factors, typified by protein A, which binds the Fc component of immunoglobulin G.Since the identification of agr (20), models of staphylococcal virulence have assig...

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Section: Discussionmentioning

confidence: 99%

Repression of the Staphylococcus aureus Accessory Gene Regulator in Serum and In Vivo

et al. 2002

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“…The global regulators agr and sar, which control the density-dependent production of S. aureus adhesins and toxins, are critical for the intraocular virulence of S. aureus. Infections in eyes inoculated with strains deficient in agr, sar, or both global regulators were highly attenuated (Booth, et al, 1995(Booth, et al, ,1997Giese, et al, 1999), more so than that observed during infection with staphylococcal strains deficient individual toxins.…”

Section: Staphylococcusmentioning

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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“…Evidence concerning the contribution of bacterial toxins to endophthalmitis demonstrates that in some cases, single toxins are the primary virulence factors (e.g., the Enterococcus faecalis cytolysin [21]). In other cases, multiple toxins work synergistically to achieve virulence (e.g., S. aureus toxins governed by the agr-sar quorum-sensing system [6,16]). In a manner similar to S. aureus virulence factor regulation, production of a number of Bacillus toxins is controlled by the transcriptional regulator plcR.…”

Section: Discussionmentioning

confidence: 99%

Relationship of plcR -Regulated Factors to Bacillus Endophthalmitis Virulence

Callegan

Kane²,

Cochran³

et al. 2003

Infect Immun

100

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The explosive, destructive course of Bacillus endophthalmitis has been attributed to the production of toxins during infection. In this study we analyzed the contribution of toxins controlled by the global regulator plcR to the pathogenesis of experimental Bacillus endophthalmitis. Isogenic plcR-deficient mutants of Bacillus cereus and Bacillus thuringiensis were constructed by insertional inactivation of plcR by the kanamycin resistance cassette, aphA3. Rabbit eyes were injected intravitreally with approximately 100 CFU of wild-type B. cereus or B. thuringiensis or a plcR-deficient mutant. The evolution of endophthalmitis resulting from each plcR-deficient mutant was considerably slower than that caused by each wild-type strain. Retinal function was not eliminated until 42 h postinfection in rabbits with endophthalmitis caused by the plcR-deficient mutants, whereas wild-type infections resulted in a complete loss of retinal function within 18 h. The intraocular inflammatory cell influx and retinal destruction in plcR-deficient endophthalmitis approached the severity observed in wild-ype infections, but not until 36 h postinfection. Gross and histological examinations of eyes infected with plcR mutants demonstrated that the anterior and posterior segment changes were muted compared to the changes observed in eyes infected with the wild types. The loss of plcR-regulated factors significantly attenuated the severity of Bacillus endophthalmitis. The results therefore suggest that plcR may represent a target for which adjunct therapies could be designed for the prevention of blindness during Bacillus endophthalmitis.

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A comparison of the early inflammatory effects of an agr-/sar- versus a wild type strain of Staphylococcus aureus in a rat model of endophthalmitis

Cited by 23 publications

References 11 publications

Repression of the Staphylococcus aureus Accessory Gene Regulator in Serum and In Vivo

Repression of the Staphylococcus aureus Accessory Gene Regulator in Serum and In Vivo

Bacterial endophthalmitis: Therapeutic challenges and host–pathogen interactions

Relationship of plcR -Regulated Factors to Bacillus Endophthalmitis Virulence

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