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The Streptococcus sanguinis competence regulon is not required for infective endocarditis virulence in a rabbit model.

Callahan JE, Munro CL, Kitten T - PLoS ONE (2011)

Bottom Line: Strains deleted for the comCDE or comX master regulatory genes were created.These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model.We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species.

View Article: PubMed Central - PubMed

Affiliation: VCU Philips Institute of Oral and Craniofacial Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America.

ABSTRACT
Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility in S. sanguinis. Strains deleted for the comCDE or comX master regulatory genes were created. Using a rabbit endocarditis model in conjunction with a variety of virulence assays, we determined that both mutants possessed infectivity equivalent to that of a virulent control strain, and that measures of disease were similar in rabbits infected with each strain. These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model. We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species.

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Assessment of IE pathology in rabbits inoculated with JFP36 or com mutants.Rabbits were inoculated with 108 CFU of JFP36, JFP49 (comCDE), or JFP45 (comX). Data were combined from two separate experiments, each of which included all three strains. (A) Survival curve. (B) Total weight loss 5 days post-infection. Horizontal dashed line represents no weight loss. (C) Mass of aortic valve vegetations 5 days post-infection. For B and C, each symbol represents the value from a single rabbit, and horizontal lines indicated median values. No significant differences among strains were observed in any of the analyses.
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pone-0026403-g002: Assessment of IE pathology in rabbits inoculated with JFP36 or com mutants.Rabbits were inoculated with 108 CFU of JFP36, JFP49 (comCDE), or JFP45 (comX). Data were combined from two separate experiments, each of which included all three strains. (A) Survival curve. (B) Total weight loss 5 days post-infection. Horizontal dashed line represents no weight loss. (C) Mass of aortic valve vegetations 5 days post-infection. For B and C, each symbol represents the value from a single rabbit, and horizontal lines indicated median values. No significant differences among strains were observed in any of the analyses.

Mentions: We also examined pathology resulting from infection by comparing mortality, weight loss, and vegetation mass among the groups of rabbits. As mentioned above, two rabbits each inoculated with comCDE and comX mutants died on day four, while all rabbits infected with JFP36 survived until day 5 (Fig. 2A). Kaplan-Meier survival analysis indicated there was no significant difference in mortality among the groups. Since weight loss has previously been shown to be a reliable indicator of IE severity in a rabbit model [27], infected rabbits were weighed daily throughout the study. As shown in Fig. 2B, total weight loss after five days of infection did not differ significantly among rabbits infected with each strain. Likewise, no significant differences among groups were observed on days 1–4 post-infection (data not shown). Fig. 2C shows the masses of vegetations recovered at the end of the five-day infection. Our results indicated no significant differences in vegetation mass for rabbits infected with each of the three strains. Further, no consistent morphological differences were observed upon gross examination of the vegetations (data not shown). Taken together, our results suggest that the S. sanguinis com regulon is not required for IE virulence or pathology in the rabbit model under a variety of assay conditions.


The Streptococcus sanguinis competence regulon is not required for infective endocarditis virulence in a rabbit model.

Callahan JE, Munro CL, Kitten T - PLoS ONE (2011)

Assessment of IE pathology in rabbits inoculated with JFP36 or com mutants.Rabbits were inoculated with 108 CFU of JFP36, JFP49 (comCDE), or JFP45 (comX). Data were combined from two separate experiments, each of which included all three strains. (A) Survival curve. (B) Total weight loss 5 days post-infection. Horizontal dashed line represents no weight loss. (C) Mass of aortic valve vegetations 5 days post-infection. For B and C, each symbol represents the value from a single rabbit, and horizontal lines indicated median values. No significant differences among strains were observed in any of the analyses.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198404&req=5

pone-0026403-g002: Assessment of IE pathology in rabbits inoculated with JFP36 or com mutants.Rabbits were inoculated with 108 CFU of JFP36, JFP49 (comCDE), or JFP45 (comX). Data were combined from two separate experiments, each of which included all three strains. (A) Survival curve. (B) Total weight loss 5 days post-infection. Horizontal dashed line represents no weight loss. (C) Mass of aortic valve vegetations 5 days post-infection. For B and C, each symbol represents the value from a single rabbit, and horizontal lines indicated median values. No significant differences among strains were observed in any of the analyses.
Mentions: We also examined pathology resulting from infection by comparing mortality, weight loss, and vegetation mass among the groups of rabbits. As mentioned above, two rabbits each inoculated with comCDE and comX mutants died on day four, while all rabbits infected with JFP36 survived until day 5 (Fig. 2A). Kaplan-Meier survival analysis indicated there was no significant difference in mortality among the groups. Since weight loss has previously been shown to be a reliable indicator of IE severity in a rabbit model [27], infected rabbits were weighed daily throughout the study. As shown in Fig. 2B, total weight loss after five days of infection did not differ significantly among rabbits infected with each strain. Likewise, no significant differences among groups were observed on days 1–4 post-infection (data not shown). Fig. 2C shows the masses of vegetations recovered at the end of the five-day infection. Our results indicated no significant differences in vegetation mass for rabbits infected with each of the three strains. Further, no consistent morphological differences were observed upon gross examination of the vegetations (data not shown). Taken together, our results suggest that the S. sanguinis com regulon is not required for IE virulence or pathology in the rabbit model under a variety of assay conditions.

Bottom Line: Strains deleted for the comCDE or comX master regulatory genes were created.These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model.We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species.

View Article: PubMed Central - PubMed

Affiliation: VCU Philips Institute of Oral and Craniofacial Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America.

ABSTRACT
Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility in S. sanguinis. Strains deleted for the comCDE or comX master regulatory genes were created. Using a rabbit endocarditis model in conjunction with a variety of virulence assays, we determined that both mutants possessed infectivity equivalent to that of a virulent control strain, and that measures of disease were similar in rabbits infected with each strain. These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model. We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species.

Show MeSH
Related in: MedlinePlus