Disruption of the NlpD lipoprotein of the plague pathogen Yersinia pestis affects iron acquisition and the activity of the twin-arginine translocation system

Abstract

We have previously shown that the cell morphogenesis NlpD lipoprotein is essential for virulence of the plague bacteria, Yersinia pestis . To elucidate the role of NlpD in Y . pestis pathogenicity, we conducted a whole-genome comparative transcriptome analysis of the wild-type Y . pestis strain and an nlpD mutant under conditions mimicking early stages of infection. The analysis suggested that NlpD is involved in three phenomena: (i) Envelope stability/integrity evidenced by compensatory up-regulation of the Cpx and Psp membrane stress-response systems in the mutant; (ii) iron acquisition, supported by modulation of iron metabolism genes and by limited growth in iron-deprived medium; (iii) activity of the twin-arginine (Tat) system, which translocates folded proteins across the cytoplasmic membrane. Virulence studies of Y . pestis strains mutated in individual Tat components clearly indicated that the Tat system is central in Y . pestis pathogenicity and substantiated the assumption that NlpD essentiality in iron utilization involves the activity of the Tat system. This study reveals a new role for NlpD in Tat system activity and iron assimilation suggesting a modality by which this lipoprotein is involved in Y . pestis pathogenesis.

The lipoprotein NlpD in Cronobacter sakazakii responds to acid stress and regulates macrophage resistance and virulence by maintaining membrane integrity

“…Recently, the mip -like gene fkpA of C. sakazakii has been shown to play a role in macrophage resistance, but its role in virulence has not been elucidated [ 10 ]. Previous studies have mostly considered that nlpD is related to envelop integrity and iron acquisition [ 44–46 ]. However, a few studies reported that nlpD affects virulence in the phytopathogens Xanthomonas [ 47 ] and Yersinia pestis [ 48 ].…”

Novel RNA Extraction Method for Dual RNA-seq Analysis of Pathogen and Host in the Early Stages of Yersinia pestis Pulmonary Infection

“…The bacterial strain examined in this study was the virulent Y. pestis strain Kimberley53 (Kim53) [ 11 ]. The bacteria were used for intranasal infections, as described previously [ 12 ]. Briefly, Y. pestis bacteria were grown on BHIA plates (BD, Franklin Lakes, MD, USA) for 48 h at 28 °C, and several colonies were suspended in HIB (BD, Franklin Lakes, MD, USA) supplemented with 0.2% (+) xylose and 2.5 mM CaCl 2 (Sigma-Aldrich, St. Louis, MO, USA) and incubated overnight at 28 °C.…”

“…Prior to infection, mice were anaesthetized by intraperitoneal injection of a mixture of 0.5% ketamine HCl and 0.1% xylazine, then subjected to intranasal infection with 35 μL/mouse of the bacterial suspension. Under these conditions, the LD 50 of Y. pestis Kim53 is ~550 CFU [ 11 , 12 ]. Mice were infected with 1000 LD 50 (550,000 CFU).…”

Screening of an FDA-Approved Library for Novel Drugs against Y. pestis

“…The Y. pestis strains used in this study included the live vaccine strain EV76 ( pgm -[Girard’s strain]) and two antibiotic-resistant Y. pestis strains, ciprofloxacin-resistant strain #66-6 [ 19 ] and doxycycline-resistant strain #36-4-18 [ 18 ] derived from the avirulent parental pCD1 and pPCP1-cured Kim53 strain [ 28 , 29 ].…”