PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance.
John S. Gunn,Samuel I. Miller +1 more
431
TL;DR: Data suggest that resistance to the polymyxin-CAP family is controlled by a cascade of regulatory protein expression that activates transcription upon environmental sensing.
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Abstract: Antimicrobial cationic peptides are a host defense mechanism of many animal species including mammals, insects, and amphibians. Salmonella typhimurium is an enteric and intracellular pathogen that interacts with antimicrobial peptides within neutrophil and macrophage phagosomes and at intestinal mucosal surfaces. The Salmonella spp. virulence regulators, PhoP and PhoQ, activate the transcription of genes (pag) within macrophage phagosomes necessary for resistance to cationic antimicrobial peptides. One PhoP-activated gene, pagB, forms an operon with pmrAB (5' pagB-pmrA-pmrB 3'), a two-component regulatory system involved in resistance to the antimicrobial peptides polymyxin, azurocidin (CAP37), bactericidal/permeability-increasing protein (BPI or CAP57), protamine, and polylysine. Expression of pmrAB increased transcription of pagB-pmrAB by activation of a promoter 5' to pagB. pmrAB is also expressed from a second promoter, not regulated by PhoP-PhoQ or PmrA-PmrB, located within the pagB coding sequence. S. typhimurium strains with increased pag locus expression were demonstrated to be polymyxin resistant because of induction of pagB-pmrAB; however, PmrA-PmrB was not responsible for the increased sensitivity of PhoP-null mutants to NP-1 defensin. Therefore, PhoP regulates at least two separate networks of genes responsible for cationic antimicrobial peptide resistance. These data suggest that resistance to the polymyxin-CAP family is controlled by a cascade of regulatory protein expression that activates transcription upon environmental sensing.
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References
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TL;DR: Autoregulation of the phoPQ operon provides several levels of control for the PhoP-PhoQ regulon, and was observed at the protein level with anti-PhOP antibodies.
Molecular genetic analysis of a locus required for resistance to antimicrobial peptides in Salmonella typhimurium.
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242
Characterization of the lipopolysaccharide from the polymyxin-resistant pmrA mutants of Salmonella typhimurium.
Martti Vaara,T. Vaara,Michael Jensen,Ilkka M. Helander,Marjatta Nurminen,E.Th. Rietschel,P.H. Mäkelä +6 more
TL;DR: Here it is shown that S. typhimurium mutants (pmrA mutants) represent a novel type of mutation affecting the lipid A structure: the esterlinked phosphate in their lipid A is almost completely substituted with 4-ARAN, and their LPS has also an increased content of ethanolamine.
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Spontaneous pmrA mutants of Salmonella typhimurium LT2 define a new two-component regulatory system with a possible role in virulence.
TL;DR: DNA sequence analysis of the pmrA505 clone revealed three open reading frames (ORFs) and deduced amino acid sequences indicated that ORF1 encodes a 548-amino-acid protein with a putative membrane-spanning domain and no significant homology to any known protein, while ORF2 and ORF3 show strong homology with the OmpR-EnvZ family of two-component regulatory systems.
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TL;DR: One aspect of research on oxygen-independent mechanisms, the antibiotic proteins of human neutrophils, comprises at least three structurally different families that share the capacity to kill bacteria independent of oxygen and evidently, contrary to Metchnikov's conjecture, to do so independent of enzymic action.