Smd. Bearson et al., ACID SHOCK INDUCTION OF RPOS IS MEDIATED BY THE MOUSE VIRULENCE GENE MVIA OF SALMONELLA-TYPHIMURIUM, Journal of bacteriology, 178(9), 1996, pp. 2572-2579
Salmonella typhimurium encounters a variety of acid stress situations
during growth in host and nonhost environments, The organism can survi
ve potentially lethal acid conditions (pH <4) if it is first able to a
dapt to mild or more moderate acid levels. The molecular events that o
ccur during this adaptive process are collectively referred to as the
acid tolerance response and vary depending on whether the cells are in
log- or stationary-phase growth. The acid tolerance response of logar
ithmically growing cells includes the participation of an alternate si
gma factor, sigma(S) (RpoS), commonly associated with stationary-phase
physiology. Of 51 acid shock proteins (ASPs) induced during shifts to
pH 4.4, 8 are clearly dependent on sigma(S) for production (I. S. Lee
, J. Lin, H. K. Hall, B. Bearson, and J. W. Foster, Mol. Microbiol. 17
:155-167, 1995). The acid shock induction of these proteins appears to
be the result of an acid shock-induced increase in the level of sigma
(S) itself. We have discovered that one component of a potential signa
l transduction system responsible for inducing rpoS expression is the
product of the mouse virulence gene mviA(+). MviA exhibits extensive h
omology to the regulatory components of certain two-component signal t
ransduction systems (W. H. Benjamin, Jr., and P. D. Hall, abstr. B-67,
p. 38, in Abstracts of the 93rd General Meeting of the American Socie
ty for Microbiology 1993, 1993), Mutations in mviA (mviA::Km) caused t
he overproduction of sigma(S) and sigma(S)-dependent ASPs in logarithm
ically growing cells, as well as increases in tolerances to acid, heat
, osmolarity, and oxidative stresses and significant decreases in grow
th rate and colony size. Mutations in rpoS suppressed the mviA::Km-ass
ociated defects in growth rate, colony size, ASP production, and stres
s tolerance, suggesting that the effects of MviA on cell physiology oc
cur via its control of sigma(S) levels. Western blot (immunoblot) anal
yses of sigma(S) produced from natural or arabinose-regulated promoter
s revealed that acid shock and MviA posttranscriptionally regulate sig
ma(S) levels. Turnover experiments suggest that MviA regulates the sta
bility of sigma(S) protein rather than the translation of rpoS message
. We propose a model in which MviA or its unknown signal transduction
partner senses some consequence of acid shock, and probably other stre
sses, and signals the release of sigma(S) from proteolysis. The increa
sed concentration of sigma(S) drives the elevated expression of the si
gma(S)-dependent ASPs, resulting in an increase in stress tolerance, T
he avirulent nature of mviA insertion mutants, therefore, appears to r
esult from inappropriate sigma(S)-dependent gene expression during pat
hogenesis.