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Journal of Bacteriology, June 1999, p. 3525-3535, Vol. 181, No. 11
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Control of Acid Resistance in
Escherichia coli
Marie-Pierre
Castanie-Cornet,1
Thomas A.
Penfound,1,
Dean
Smith,2,
John F.
Elliott,2 and
John W.
Foster1,*
Department of Microbiology and Immunology,
University of South Alabama College of Medicine, Mobile, Alabama
36688,1 and Department of Medical
Microbiology and Immunology, University of Alberta, Edmonton,
Alberta, Canada T6G 2S22
Received 3 February 1999/Accepted 26 March 1999
Acid resistance (AR) in Escherichia coli is defined as
the ability to withstand an acid challenge of pH 2.5 or less and is a
trait generally restricted to stationary-phase cells. Earlier reports
described three AR systems in E. coli. In the present study, the genetics and control of these three systems have been more
clearly defined. Expression of the first AR system (designated the
oxidative or glucose-repressed AR system) was previously shown to
require the alternative sigma factor RpoS. Consistent with glucose
repression, this system also proved to be dependent in many situations
on the cyclic AMP receptor protein. The second AR system required the
addition of arginine during pH 2.5 acid challenge, the structural gene
for arginine decarboxylase (adiA), and the regulator
cysB, confirming earlier reports. The third AR system
required glutamate for protection at pH 2.5, one of two genes encoding
glutamate decarboxylase (gadA or gadB), and the
gene encoding the putative glutamate:
-aminobutyric acid antiporter (gadC). Only one of the two glutamate decarboxylases was
needed for protection at pH 2.5. However, survival at pH 2 required
both glutamate decarboxylase isozymes. Stationary phase and acid pH regulation of the gad genes proved separable.
Stationary-phase induction of gadA and gadB
required the alternative sigma factor
S encoded by
rpoS. However, acid induction of these enzymes, which was
demonstrated to occur in exponential- and stationary-phase cells,
proved to be
S independent. Neither gad gene
required the presence of volatile fatty acids for induction. The data
also indicate that AR via the amino acid decarboxylase systems requires
more than an inducible decarboxylase and antiporter. Another surprising
finding was that the
S-dependent oxidative system,
originally thought to be acid induced, actually proved to be induced
following entry into stationary phase regardless of the pH. However, an
inhibitor produced at pH 8 somehow interferes with the activity of this
system, giving the illusion of acid induction. The results also
revealed that the AR system affording the most effective protection at
pH 2 in complex medium (either Luria-Bertani broth or brain heart
infusion broth plus 0.4% glucose) is the glutamate-dependent GAD
system. Thus, E. coli possesses three overlapping acid
survival systems whose various levels of control and differing
requirements for activity ensure that at least one system will be
available to protect the stationary-phase cell under naturally
occurring acidic environments.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, University of South Alabama College of
Medicine, Medical Sciences Building, Mobile, AL 36688. Phone: (334)
460-6323. Fax: (334) 460-7931. E-mail:
fosterj{at}sungcg.usouthal.edu.

Present address: Department of Infectious Diseases, St. Jude
Children's Research Hospital, Memphis, TN
38105.

Present address: Vaccine Design Group, Institute for Biological
Sciences, National Research Council, Ottawa, Ontario, Canada
K1A
0R6.
Journal of Bacteriology, June 1999, p. 3525-3535, Vol. 181, No. 11
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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