We have recently established that the PhoP-activated ugtL gene is required for resistance to the antimicrobial peptides magainin 2 and polymyxin B .
The ugtL gene is part of a Salmonella-specific gene cluster that includes the PhoP-activated pcgL gene ( 22 ) and the sifB gene , which is expressed in response to the low Mg2 conditions that normally activate the PhoP/PhoQ system ( 23 ) .
Transcriptional Activation of the ugtL Promoter -- The majority of PhoP-activated promoters described to date harbor a conserved hexanucleotide repeat separated by 5 nucleotides , termed the PhoP box , located 12 bp upstream of the 10 region ( 14 ) .
We have demonstrated recently that the PhoP-activated ugtL gene is required for a modification of the lipid-A mediating resistance to the antimicrobial peptides magainin 2 and poly-myxin B ( 21 ) .
the ugtL promoter _ performed with increasing amounts of PhoP proteins
the ugtL promoter _ performed with increasing amounts of the PhoP protein
One of the clones harboured the PhoP-activated ugtL gene , deletion of which rendered Salmonella susceptible to magainin 2 and polymyxin B , but not defensin HNP-1 .
Three of the plasmids harboured two complete Salmonella-specific open reading frames ( ORFs ) : ugtL , a PhoP-activated gene of unknown function ( Hilbert et al. , 1999 ) ; and STM1600 , an uncharacterized ORF .
The PhoP-activated ugtL , pagP and yqjA genes are required for resistance to the alpha-helical peptides magainin 2 and cecropin A but not to the b-sheet defensin HNP-1 .
Cumulatively , these results demonstrate that yqjA is a PhoP-activated gene required for magainin 2 resistance and that yqjA confers magainin resistance by a pathway that is different from those mediated by the ugtL and pagP genes .
The ugtL gene was first identified as part of a Salmonella-specific DNA region harbouring the PhoP-activated pcgL gene , which encodes a D-Ala-D-Ala dipeptidase ( Hilbert et al. , 1999 ) .
We determined that a ugtL pmrA double mutant was as susceptible to polymyxin B as a phoP mutant ( Fig. 3C ) , which suggests that both types of lipid-A modifications may operate at the same time and argues against the participation of other PhoP-regulated genes in resistance to polymxyin B. Thus , the increased polymyxin B susceptibility reported for mutants defective in the PhoP-activated mig-14 , virK and somA genes may be characteristic of the SL1344 genetic background used in those studies ( Brodsky et al. , 2002 ; Detweiler et al. , 2003 ) because derivatives of the 14028s strain deleted for the mig-14 gene or harbouring a MudJ transposon insertion in the virK gene retained wild-type resistance to both polymxyin B and magainin 2 ( our unpublished results ) .
We establish that the PhoP-activated ugtL gene is required for resistance to magainin 2 and poly-myxin B , and determine that it encodes an inner membrane protein needed for the modification of the lipid-A .
both ugtL is post-tran-scriptionally activated by the PhoP
To activate transcription of ugtL , both PhoP must bind to its promoter simultaneously .
otes time-dependent resistance to polymyxin B MgtA prom The PhoP-activated pmrD and ugtL genes encode products mediating the chemical modification of negatively charged residues in the lipopolysaccharide ( LPS ) , thereby conferring resistance to the cationic peptide antibiotic polymyxin B ( Kox et al. , 2000 ; Shi et al. , 2004 ) .