The Biology of the PmrA/PmrB Two-Component System: The Major Regulator of Lipopolysaccharide Modifications

Abstract

The ability of gram-negative bacteria to resist killing by antimicrobial agents and to avoid detection by host immune systems often entails modification to the lipopolysaccharide (LPS) in their outer membrane. In this review, we examine the biology of the PmrA/PmrB two-component system, the major regulator of LPS modifications in the enteric pathogen Salmonella enterica. We examine the signals that activate the sensor PmrB and the targets controlled by the transcriptional regulator PmrA. We discuss the PmrA/PmrB-dependent chemical decorations of the LPS and their role in resistance to antibacterial agents. We analyze the feedback mechanisms that modulate the activity and thus output of the PmrA/PmrB system, dictating when, where, and to what extent bacteria modify their LPS. Finally, we explore the qualitative and quantitative differences in gene expression outputs resulting from the distinct PmrA/PmrB circuit architectures in closely related bacteria, which may account for their differential survival in various ecological niches.

Transcriptional regulation of the Aggregatibacter actinomycetemcomitans ygiW–qseBC operon by QseB and integration host factor proteins

“…S2, the A. actinomycetemcomitans QseB is structurally highly similar to other members of the OmpR/ PhoB response regulators, and shares the phosphorylation domain, dimer interface and DNA contact motifs that are present in these transcriptional regulators. The DNA sequences recognized by the OmpR/PhoB subfamily have been determined for many members and all bind to specific DNA direct repeat sequences (Chen & Groisman, 2013;Liu & De Wulf, 2004;Yamamoto & Ishihama, 2006;Zwir et al, 2012;Rhee et al, 2008;Ritzefeld et al, 2013;Tung & McMahon, 2012), consistent with our finding that CTTAA direct repeats represent the QseB binding site of A. actinomycetemcomitans. Phosphorylation of this subfamily of response regulators induces the formation of dimers, which increase the binding affinity of the Cterminal DNA-binding domain with the tandem DNA direct repeat sequences on the promoters of target genes (Toro-Roman et al, 2005;Creager-Allen et al, 2013;Barbieri et al, 2013).…”

“…Interestingly, the sequence of this region of probe VIII contains two direct repeats separated by six nucleotides (CTTAA-N 6 -CTTAA) at nucleotides 278 to 293 (see Fig. S1) and this sequence resembles the DNA-binding site [CTTAA(G or T)-N 5 -CTTAA(G or T)] for the E. coli transcriptional activator PmrA, which is related to QseB (Chen & Groisman, 2013). To confirm that this putative QseB binding site regulates ygiW-qseBC expression, pDJR57 containing nucleotides 21 to 2122 (see Fig.…”

Deciphering the Metabolism of Undecaprenyl-Phosphate: The Bacterial Cell-Wall Unit Carrier at the Membrane Frontier

“…Under certain circumstances, such as the presence of a high concentration of Fe 3 + in the extracellular medium, the twocomponent system PmrA/PmrB induces the expression of ArnT and EptA, which in contrast to LpxT neutralize lipid A phosphate negative charges through the addition of positively charged amino groups. 17,77 Indeed, ArnT 107 and EptA 60 specifically catalyze the addition of 4-amino-4-deoxy-L-arabinose (L-Ara4N) and phosphoethanolamine (pEtN) to the monophosphate groups at the 4¢ and 1 positions of lipid A, respectively. These modifications confer resistance to Fe 3 + and cationic antibacterial peptides (CAMPs) such as polymyxin B by limiting their binding to the cell surface.…”

“…70 This led to the hypothesis that YbjG expressed in these conditions may compensate for the lack of LpxT in the (re)generation of the C 55 -P carrier lipid. 17 In Cupriavidus metallidurans CH34, a PAP2 phosphatase-encoding gene, named pbrB, was detected within a gene cluster known to participate in a lead resistance mechanism. 46 This cluster, pbrTRABCD, was carried on a megaplasmid and consisted of two divergently transcribed operons: pbrTR and pbrABCD.…”

Avaliação da relação genética e perfil de sensibilidade de <i>Klebsiella pneumoniae</i> resistentes à polimixina B

“…Encontra-se na figura 2 uma representação esquemática desse sistema de sinalização (CHEN; GROISMAN, 2013 Escherichia coli com sucesso na transmissão horizontal da resistência à colistina e com estabilidade mesmo sem a pressão seletiva das polimixinas (LIU et al, 2015). Observou-se a presença do mcr-1 em isolados de E. coli recolhidos de 15% de 523 amostras de carne para consumo humano, em 21% de 804 animais de corte (frango e suínos) durante 2011 a 2014, e 16 entre 1.322 amostras de pacientes com infecção, sendo três isolados de Klebsiella pneumoniae.…”