Affiliation:
1. Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
Abstract
ABSTRACT
Bacterial pathogenesis depends on changes in metabolic and virulence gene expression in response to changes within a pathogen's environment. The plague-causing pathogen,
Yersinia pestis
, requires expression of the gene encoding the Pla protease for progression of pneumonic plague. The catabolite repressor protein Crp, a global transcriptional regulator, may serve as the activator of
pla
in response to changes within the lungs as disease progresses. By using gene reporter fusions, the spatial and temporal activation of the
crp
and
pla
promoters was measured in a mouse model of pneumonic plague. In the lungs,
crp
was highly expressed in bacteria found within large aggregates resembling biofilms, while
pla
expression increased over time independent of the aggregated state. Increased expression of
crp
and
pla
correlated with a reduction in lung glucose levels. Deletion of the glucose-specific phosphotransferase system EIIBC (PtsG) of
Y. pestis
rescued glucose levels in the lungs, resulting in reduced expression of both
crp
and
pla
. We propose that activation of
pla
expression during pneumonic plague is driven by an increase of both Crp and cAMP levels following consumption of available glucose in the lungs by
Y. pestis
. Thus, Crp operates as a sensor linking the nutritional environment of the host to regulation of virulence gene expression.
IMPORTANCE
Using
Yersinia pestis
as a model for pneumonia, we discovered that glucose is rapidly consumed, leading to a catabolite-repressive environment in the lungs. As a result, expression of the gene encoding the plasminogen activator protease, a target of the catabolite repressor protein required for
Y. pestis
pathogenesis, is activated. Interestingly, expression of the catabolite repressor protein itself was also increased in the absence of glucose but only in biofilms. The data presented here demonstrate how a bacterial pathogen senses changes within its environment to coordinate metabolism and virulence gene expression.
Funder
HHS | NIH | National Institute of Allergy and Infectious Diseases
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
7 articles.
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