Affiliation:
1. Department of Microbiology, University of Georgia, Athens, Georgia, USA
Abstract
ABSTRACT
Soil is a complex niche, where survival of microorganisms is at risk due to the presence of antimicrobial agents. Many microbes chemically modify cytotoxic compounds to block their deleterious effects. Streptothricin is a broad-spectrum antibiotic produced by streptomycetes that affects Gram-positive and Gram-negative bacteria alike. Here we identify the SatA (for
s
treptothricin
a
ce
t
yltransferase
A
, formerly YyaR) enzyme of
Bacillus subtilis
as the mechanism used by this soil bacterium to detoxify streptothricin.
B. subtilis
strains lacking
satA
were susceptible to streptothricin. Ectopic expression of
satA
+
restored streptothricin resistance to
B. subtilis
satA
(
Bs
SatA) strains. Purified
Bs
SatA acetylated streptothricin
in vitro
at the expense of acetyl-coenzyme A (acetyl-CoA). A single acetyl moiety transferred onto streptothricin by SatA blocked the toxic effects of the antibiotic. SatA bound streptothricin with high affinity (
K
d
[dissociation constant] = 1 μM), and did not bind acetyl-CoA in the absence of streptothricin. Expression of
B. subtilis
satA
+
in
Salmonella enterica
conferred streptothricin resistance, indicating that SatA was necessary and sufficient to detoxify streptothricin. Using this heterologous system, we showed that the SatA homologue from
Bacillus anthracis
also had streptothricin acetyltransferase activity. Our data highlight the physiological relevance of lysine acetylation for the survival of
B. subtilis
in the soil.
IMPORTANCE
Experimental support is provided for the functional assignment of gene products of the soil-dwelling bacilli
Bacillus subtilis
and
Bacillus anthracis
. This study focuses on one enzyme that is necessary and sufficient to block the cytotoxic effects of a common soil antibiotic. The enzyme alluded to is a member of a family of proteins that are broadly distributed in all domains of life but poorly studied in
B. subtilis
and
B. anthracis
. The initial characterization of the enzyme provides insights into its mechanism of catalysis.
Funder
HHS | NIH | National Institute of General Medical Sciences
Publisher
American Society for Microbiology
Subject
Ecology,Applied Microbiology and Biotechnology,Food Science,Biotechnology
Cited by
13 articles.
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