Effects of regulatory network organization and environment on PmrD connector activity and polymyxin resistance in Klebsiella pneumoniae and Escherichia coli.

Effects of regulatory network organization and environment on PmrD connector activity and polymyxin resistance in Klebsiella pneumoniae and Escherichia coli. Antimicrob Agents Chemother. 2020 Dec 23;: Authors: Chen AI, Albicoro FJ, Zhu J, Goulian M Abstract Polymyxins are a class of cyclic peptides with antimicrobial activity against Gram-negative bacteria. In Enterobacteriaceae, the PhoQ/PhoP and PmrB/PmrA two-component systems regulate many genes that confer resistance to both polymyxins and host antimicrobial peptides. The activities of these two-component systems are modulated by additional proteins that are conserved across Enterobacteriaceae, such as MgrB, a negative regulator of PhoQ, and PmrD, a "connector" protein that activates PmrB/PmrA in response to PhoQ/PhoP stimulation. Despite the conservation of many protein components of the PhoQ/PhoP-PmrD-PmrB/PmrA network, the specific molecular interactions and regulatory mechanisms vary across different genera. Here we explore the role of PmrD in modulating this signaling network in Klebsiella pneumoniae and Escherichia coli We show that in K. pneumoniae, PmrD is not required for polymyxin resistance arising from mutation of mgrB-the most common cause of spontaneous polymyxin resistance in this bacterium-suggesting that direct activation of polymyxin resistance genes by PhoQ/PhoP plays a critical role in this resistance pathway. However, for conditions of low pH or intermediate ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research