Temperature sensing in Yersinia pestis: translation of the LcrF activator protein is thermally regulated.

J Bacteriol

Department of Molecular Genetics and Microbiology, University of Masschusetts Medical Center, Worcester 01655.

Published: December 1993

The lcrF gene of Yersinia pestis encodes a transcription activator responsible for inducing expression of several virulence-related proteins in response to temperature. The mechanism of this thermoregulation was investigated. An lcrF clone was found to produce much lower levels of LcrF protein at 26 than at 37 degrees C in Y. pestis, although it was transcribed at similar levels at both temperatures. High-level T7 polymerase-directed transcription of the lcrF gene in Escherichia coli also resulted in temperature-dependent production of the LcrF protein. Pulse-chase experiments showed that the LcrF protein was stable at 26 and 37 degrees C, suggesting that translation rate or message degradation is thermally controlled. The lcrF mRNA appears to be highly unstable and could not be reliably detected in Y. pestis. Insertion of the lcrF gene into plasmid pET4a, which produces high levels of plasmid-length RNA, aided detection of lcrF-specific message in E. coli. Comparison of the amount of LcrF protein produced per unit of message at 26 and 37 degrees C indicated that the efficiency of translation of lcrF message increased with temperature. mRNA secondary structure predictions suggest that the lcrF Shine-Dalgarno sequence is sequestered in a stem-loop. A model in which decreased stability of this stem-loop with increasing temperature leads to increased efficiency of translation initiation of lcrF message is presented.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC206968PMC
http://dx.doi.org/10.1128/jb.175.24.7901-7909.1993DOI Listing

Publication Analysis

Top Keywords

lcrf protein
16
lcrf
13
lcrf gene
12
yersinia pestis
8
translation lcrf
8
efficiency translation
8
lcrf message
8
protein
5
message
5
temperature
4

Similar Publications

Despite the established use of immune checkpoint inhibitors (ICIs) to treat non-small cell lung cancer (NSCLC), only a subset of patients benefit from treatment and ∼50% of patients whose tumors respond eventually develop acquired resistance (AR). To identify novel drivers of AR, we generated murine Msh2 knock-out (KO) lung tumors that initially responded but eventually developed AR to anti-PD-1, alone or in combination with anti-CTLA-4. Resistant tumors harbored decreased infiltrating T cells and reduced cancer cell-intrinsic MHC-I and MHC-II levels, yet remained responsive to IFNγ.

View Article and Find Full Text PDF
Article Synopsis
  • SARS-CoV-2, responsible for COVID-19, has caused over 7 million deaths worldwide since its emergence, leading to trials of treatments like the anti-IL6 inhibitor tocilizumab, which failed to significantly improve survival rates.
  • Researchers isolated extracellular vesicles (EVs) from 39 severe COVID-19 patients to explore their potential as biomarkers, finding that specific viral proteins (spike and nucleocapsid) were dynamic in expression during treatment and recovery.
  • The study suggests that the changing levels of EV viral proteins could correlate with clinical outcomes, indicating that EVs might help identify long COVID and other complications in patients with severe cases.
View Article and Find Full Text PDF

Introduction: Identifying mutations in the epidermal growth factor receptor (EGFR) gene is crucial for individualized treatment of non-small cell lung cancer (NSCLC) patients. Accordingly, several methodologies and instruments are now commercially available to detect these alterations. The aim of this study was to examine the performance of next generation sequencing (NGS) in detecting both common and uncommon EGFR gene mutations in advanced NSCLC patients.

View Article and Find Full Text PDF

Purpose: The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma.

Patients And Methods: A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network.

View Article and Find Full Text PDF

Introduction: With multiple targeted therapies approved for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), it is increasingly important to understand outcomes with various sequences of next-generation ALK tyrosine kinase inhibitors (TKIs). We describe contemporary sequencing patterns and treatment effectiveness of first-line (1L) and second-line (2L) treatments in patients who received second-generation ALK TKIs in the 1L treatment of ALK-positive NSCLC in the United States.

Methods: A cohort of adults with ALK-positive advanced NSCLC who initiated treatment with 1L alectinib or brigatinib between June 2017 and April 2021 in the Flatiron Health electronic health record-derived de-identified database were followed through April 2023.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!