PMID:21149452

Citation	Weatherspoon-Griffin, N, Zhao, G, Kong, W, Kong, Y, Morigen, H, Andrews-Polymenis, M, McClelland, Y and Shi, (2011) The CpxR/CpxA two-component system up-regulates two Tat-dependent peptidoglycan amidases to confer bacterial resistance to antimicrobial peptide.J. Biol. Chem. 286:5529-39
Abstract	We demonstrate that the twin arginine translocation (Tat) system contributes to bacterial resistance to cationic antimicrobial peptides (CAMPs). Our results show that a deletion at the tatC gene, which encodes a subunit of the Tat complex, caused Salmonella and Escherichia coli to become susceptible to protamine. We screened chromosomal loci that encode known and predicted Tat-dependent proteins and found that two N-acetylmuramoyl-l-alanine amidases, encoded by amiA and amiC, elevated bacterial resistance to protamine and α-helical peptides magainin 2 and melittin but not to β-sheet defensin HNP-1 and lipopeptide polymyxin B. Genetic analysis suggests that transcription of both amiA and amiC loci in Salmonella is up-regulated by the CpxR/CpxA two-component system when nlpE is overexpressed. A footprinting analysis reveals that CpxR protein can interact with amiA and amiC promoters at the CpxR box, which is localized between the predicted -10 and -35 regions but present on different strands in these two genes. In addition, our results show that activation of the CpxR/CpxA system can facilitate protamine resistance because nlpE overexpression elevates this resistance in the wild-type strain but not the cpxR deletion mutant. Thus, we uncover a new transcriptional regulation pathway in which the Cpx envelope stress response system modulates the integrity of the cell envelope in part by controlling peptidoglycan amidase activity, which confers bacterial resistance to protamine and α-helical CAMPs. Our studies have important implications for understanding transcriptional regulation of peptidoglycan metabolism and also provide new insights into the role of the bacterial envelope in CAMP resistance.
Links	PubMed Online version:10.1074/jbc.M110.200352
Keywords	Antimicrobial Cationic Peptides; Bacterial Proteins; Drug Resistance, Bacterial; Escherichia coli; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Genetic Loci; N-Acetylmuramoyl-L-alanine Amidase; Promoter Regions, Genetic; Protein Kinases; Salmonella typhimurium; Up-Regulation
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Phenotype of	Taxon Information	Genotype Information (if known)	Condition Information	OMP ID	OMP Term Name	ECO ID	ECO Term Name	Notes	Status
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: K-12 Substrain: BW25113 NCBI Taxon ID: 83333	Genotype of Reference Strain: tatC Genotype of Experimental Strain : tatC(del)	Reference Condition:					Strain carrying deletion at tatC locus which encodes a subunit of the twin argenine translocation complex (tat)used for protein secretion, exhibited increased susceptibility to protamine, Alpha helical CAMPs magainin 2 and melittin. Fig 1 and 2.
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: K-12 Substrain: NCBI Taxon ID: 83333	Genotype of Reference Strain: tatA Genotype of Experimental Strain : tatA(del)	Reference Condition:					Strain carrying deletion at tatA locus which encodes a subunit of the twin argenine translocation complex (tat)used for protein secretion, exhibited increased susceptibility to protamine, Alpha helical CAMPs magainin 2 and melittin. Fig 1 and 2
	Taxon: Escherichia coli Strain: K-12 Substrain: NCBI Taxon ID: 83333	Genotype of Reference Strain: tatB Genotype of Experimental Strain : tatB(del)	Reference Condition:					Strain carrying deletion at tatB locus which encodes a subunit of the twin argenine translocation complex (tat)used for protein secretion, exhibited increased susceptibility to protamine, Alpha helical CAMPs magainin 2 and melittin. Fig 1 and 2
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: K-12 Substrain: NCBI Taxon ID: 83333	Genotype of Reference Strain: amiA Genotype of Experimental Strain : ami(del)	Reference Condition:					Increase susceptibility to protamine when compared to wild-type. fig 2.
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: Substrain: NCBI Taxon ID: 83333	Genotype of Reference Strain: amiC Genotype of Experimental Strain : amiC(del)	Reference Condition:					Increase susceptibility to protamine when compared to wild-type. fig 2.
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