Salmonella typhimurium responds to a variety of environmental stresses by a
ccumulating the alternative sigma factor sigma(S). The repertoire of sigma(
S)-dependent genes that are subsequently expressed confers tolerance to a v
ariety of potentially lethal conditions including low pH and stationary pha
se. The mechanism(s) responsible for triggering sigma(S) accumulation are o
f considerable interest, because they help to ensure survival of the organi
sm during encounters with suboptimal environments. Two genes associated wit
h regulating sigma(S) levels in S. typhimurium have been identified. The fi
rst is clpP, encoding the protease known to be responsible for degrading si
gma(S) in Escherichia coil. The second is dksA, encoding a protein of unkno
wn function not previously associated with regulating sigma(S) levels. As p
redicted, clpP mutants accumulated large amounts of sigma(S) even in log ph
ase. However, dksA mutants failed to accumulate sigma(S) in stationary phas
e and exhibited lower accumulation during acid shock in log phase. DksA app
ears to be required for the optimal translation of rpoS based upon dksA mut
ant effects on rpoS transcriptional and translational lacZ fusions. The reg
ion of rpoS mRNA between codons 8 and 73 is required to see the effects of
dksA mutations. This distinguishes the role of DksA from that of HF-I (hfq)
in rpoS translation, as the HF-I target area occurs well upstream of the r
poS start codon. DksA appears to be involved in the expression of several g
enes in addition to rpoS based on two-dimensional SDS-PAGE analysis of whol
e-cell proteins. As a result of their effects on gene expression, mutations
in clpP and dksA decreased the virulence of S. typhimurium in mice, consis
tent with a role for sigma(S) in pathogenesis.