Affiliation:
1. Department of Microbiology, University of Georgia, Athens, Georgia, USA
2. Department of Bacteriology, University of Wisconsin, Madison, Wisconsin, USA
Abstract
ABSTRACT
In
Salmonella enterica
, the reversible lysine acetylation (RLA) system is comprised of the protein acetyltransferase (Pat) and sirtuin deacetylase (CobB). RLA controls the activities of many proteins, including the acetyl coenzyme A (acetyl-CoA) synthetase (Acs), by modulating the degree of Acs acetylation. We report that IolR, a
myo
-inositol catabolism repressor, activates the expression of genes encoding components of the RLA system.
In vitro
evidence shows that the IolR protein directly regulates
pat
expression. An
iolR
mutant strain displayed a growth defect in minimal medium containing 10 mM acetate, a condition under which RLA function is critical to control Acs activity. Increased levels of Pat, CobB, or Acs activity reversed the growth defect, suggesting the Pat/CobB ratio in an
iolR
strain is altered and that such a change affects the level of acetylated, inactive Acs. Results of quantitative reverse transcription-PCR (qRT-PCR) analyses of
pat
,
cobB
, and
acs
expression indicated that expression of the genes alluded to in the IolR-deficient strain was reduced 5-, 3-, and 2.6-fold, respectively, relative to the levels present in the strain carrying the
iolR
+
allele. Acs activity in cell-free extracts from an
iolR
mutant strain was reduced ~25% relative to that of the
iolR
+
strain. Glucose differentially regulated expression of
pat
,
cobB
, and
acs
. The catabolite repressor protein (Crp) positively regulated expression of
pat
while having no effect on
cobB
.
IMPORTANCE
Reversible lysine acylation is used by cells of all domains of life to modulate the function of proteins involved in diverse cellular processes. Work reported herein begins to outline the regulatory circuitry that integrates the expression of genes encoding enzymes that control the activity of a central metabolic enzyme in C2 metabolism. Genetic analyses revealed effects on reversible lysine acylation that greatly impacted the growth behavior of the cell. This work provides the first insights into the complexities of the system responsible for controlling reversible lysine acylation at the transcriptional level in the enteropathogenic bacterium
Salmonella enterica
.
Publisher
American Society for Microbiology
Cited by
19 articles.
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