Bactericidal/permeability-increasing protein [BPI] is a cationic antim
icrobial protein from neutrophils that specifically binds to the surfa
ces of Gram-negative bacteria via the lipid A component of lipopolysac
charide. To obtain information about the responses of Salmonella typhi
murium to cell-surface damage by BPI, two-dimensional gel electrophore
sis and N-terminal microsequencing were used to identify proteins that
were induced or repressed following BPI treatment. The majority of th
e affected proteins are involved in central metabolic processes. Upon
addition of BPI, the beta-subunit of the F-1 portion of Escherichia co
il ATP synthase was repressed threefold whereas six proteins were indu
ced up to 11-fold. Three of the latter were identified as lipoamide de
hydrogenase, enoyl-acyl carrier protein reductase, and the heat-shock
protein HtpG. Additionally, a novel protein, BipA, was identified that
is induced over sevenfold by BPI; sequence analysis suggests that it
belongs to the GTPase superfamily and interacts with ribosomes. A cons
erved direct-repeat motif is present in the regulatory regions of seve
ral BPI-inducible genes, including the bipA gene. Only one of the BPI-
responsive proteins was induced when cells were treated with polymyxin
B, which also binds to lipid A. We therefore conclude that BPI and po
lymyxin B affect different global regulatory networks in S. typhimuriu
m even though they bind with high affinity to the same cell-surface co
mponent.