1. Microbiology and Infectious Disease

A frameshift in Yersinia pestis rcsD alters canonical Rcs signalling to preserve flea-mammal plague transmission cycles

  1. Xiao-Peng Guo
  2. Hai-Qin Yan
  3. Wenhui Yang
  4. Zhe Yin
  5. Viveka Vadyvaloo  Is a corresponding author
  6. Dongsheng Zhou  Is a corresponding author
  7. Yi-Cheng Sun  Is a corresponding author
  1. Chinese Academy of Medical Sciences and Peking Union Medical College, China
  2. Bengbu Medical College, China
  3. Beijing Institute of Microbiology and Epidemiology, China
  4. Washington State University, United States
https://doi.org/10.7554/eLife.83946
Share this article
Cite this article
  1. Xiao-Peng Guo
  2. Hai-Qin Yan
  3. Wenhui Yang
  4. Zhe Yin
  5. Viveka Vadyvaloo
  6. Dongsheng Zhou
  7. Yi-Cheng Sun
(2023)
A frameshift in Yersinia pestis rcsD alters canonical Rcs signalling to preserve flea-mammal plague transmission cycles
eLife 12:e83946.
https://doi.org/10.7554/eLife.83946
  2. Download BibTeX
  3. Download .RIS

Abstract

Multiple genetic changes in the enteric pathogen Yersinia pseudotuberculosis have driven the emergence of Yesinia pestis, the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenisation of rcsA, encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating Y. pestis flea-borne transmission. Additionally, rcsD, another important gene in the Rcs system, harbours a frameshift mutation. Here, we demonstrated that this rcsD mutation resulted in production of a small protein composing the C-terminal RcsD histidine-phosphotransferase domain (designated RcsD-Hpt) and full-length RcsD. Genetic analysis revealed that the rcsD frameshift mutation followed the emergence of rcsA pseudogenisation. It further altered the canonical Rcs phosphorylation signal cascade, fine-tuning biofilm production to be conducive with retention of the pgm locus in modern lineages of Y. pestis. Taken together, our findings suggest that a frameshift mutation in rcsD, is an important evolutionary step that fine-tuned biofilm production to ensure perpetuation of flea-mammal plague transmission cycles.

Data availability

All data is available within the paper, its Supporting Information files, and the NCBI GenBank. RNA-seq sequencing data can be accessed in NCBI GenBank using BioProject ID: PRJNA876755.Source data files have been provided for Figures 2D, 4B, 4D, Figures 2- figure supplement 1F and 1G.

The following data sets were generated

Article and author information

Author details

  1. Xiao-Peng Guo

    Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5745-2866

  2. Hai-Qin Yan

    Department of Basic Medical Sciences, Bengbu Medical College, Bengbu, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Wenhui Yang

    State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Zhe Yin

    State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Viveka Vadyvaloo

    Paul G Allen School for Global Health, Washington State University, Pullman, United States
    For correspondence
    vvadyvaloo@wsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4842-0525

  6. Dongsheng Zhou

    State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
    For correspondence
    zhouds@bmi.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

  7. Yi-Cheng Sun

    Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    For correspondence
    sunyc@ipbcams.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5790-7071

Funding

National Major Science and Technology Projects of China (2022YFC2303202)

  • Xiao-Peng Guo

National Natural Science Foundation of China (31700072)

  • Xiao-Peng Guo

National Natural Science Foundation of China (31670139)

  • Yi-Cheng Sun

National Natural Science Foundation of China (31800120)

  • Hai-Qin Yan

the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Project 2019HY310001)

  • Yi-Cheng Sun

the CAMS Innovation Fund for Medical Sciences (Project 2021-I2M-1-043)

  • Yi-Cheng Sun

fundamental Research Funds for the Central University (3332021092)

  • Yi-Cheng Sun

NIH Research Project Grant (R01AI117016-01A1)

  • Viveka Vadyvaloo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The animal study of flea blockage, related to Figure 5A, 5B and 5C, was performed in strict accordance with the U.S. National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals (National Research Council Committee for the Update of the Guide for the and Use of Laboratory, 2011) and as approved by the Washington State University Institutional Animal Care and Use Committee, under the Animal Subject Approval Form (ASAF) 6641 and 6396.The animal study of murine infection, related to Figure 6A, 6B and 6C, was performed in strict accordance to the Guidelines for the Welfare and Ethics of Laboratory Animals of China and all the animal experiments were approved by the Institutional Animal Care Committee (IACUC) of Academy of Military Medical Sciences (AMMS), ethical approval number IACUC-DWZX-2021-057.

Copyright

© 2023, Guo et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 697
    views
  • 148
    downloads
  • 5
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Xiao-Peng Guo
  2. Hai-Qin Yan
  3. Wenhui Yang
  4. Zhe Yin
  5. Viveka Vadyvaloo
  6. Dongsheng Zhou
  7. Yi-Cheng Sun
(2023)
A frameshift in Yersinia pestis rcsD alters canonical Rcs signalling to preserve flea-mammal plague transmission cycles
eLife 12:e83946.
https://doi.org/10.7554/eLife.83946

Share this article

https://doi.org/10.7554/eLife.83946

Categories and tags

Further reading

    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Secondary structure of the SARS-CoV-2 genome is predictive of nucleotide substitution frequency

    Zach Hensel
    Short Report

    Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern. Recently, Lan et al. reported a model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate reactivity data (Lan et al., 2022). I investigated whether base reactivities and secondary structure models derived from them can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated ‘mutational fitness’ of substitutions, a measurement of the difference between a substitution’s observed and expected frequency that is correlated with other estimates of viral fitness (Bloom and Neher, 2023). This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C→U, the most common type of substitution, I describe C→U substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.

    1. Microbiology and Infectious Disease

    Aeromonas hydrophila CobQ is a new type of NAD+- and Zn2+-independent protein lysine deacetylase

    Yuqian Wang, Guibin Wang ... Xiangmin Lin
    Research Article

    Protein NƐ-lysine acetylation (Kac) modifications play crucial roles in diverse physiological and pathological functions in cells. In prokaryotic cells, there are only two types of lysine deacetylases (KDACs) that are Zn2+- or NAD+-dependent. In this study, we reported a protein, AhCobQ, in Aeromonas hydrophila ATCC 7966 that presents NAD+- and Zn2+-independent KDAC activity. Furthermore, its KDAC activity is located in an unidentified domain (from 195 to 245 aa). Interestingly, AhCobQ has no homology with current known KDACs, and no homologous protein was found in eukaryotic cells. A protein substrate analysis showed that AhCobQ has specific protein substrates in common with other known KDACs, indicating that these KDACs can dynamically co-regulate the states of Kac proteins. Microbiological methods employed in this study affirmed AhCobQ’s positive regulation of isocitrate dehydrogenase (ICD) enzymatic activity at the K388 site, implicating AhCobQ in the modulation of bacterial enzymatic activities. In summary, our findings present compelling evidence that AhCobQ represents a distinctive type of KDAC with significant roles in bacterial biological functions.

    1. Microbiology and Infectious Disease

    A statistical framework for quantifying the nuclear export rate of influenza viral mRNAs

    Michi Miura, Naho Kiuchi ... Mineki Saito
    Research Article

    Influenza A virus transcribes viral mRNAs from the eight segmented viral genome when it infects. The kinetics of viral transcription, nuclear export of viral transcripts, and their potential variation between the eight segments are poorly characterised. Here, we introduce a statistical framework for estimating the nuclear export rate of each segment from a snapshot of in situ mRNA localisation. This exploits the cell-to-cell variation at a single time point observed by an imaging-based in situ transcriptome assay. Using our model, we revealed the variation in the mRNA nuclear export rate of the eight viral segments. Notably, the two influenza viral antigens hemagglutinin and neuraminidase were the slowest segments in the nuclear export, suggesting the possibility that influenza A virus uses the nuclear retention of viral transcripts to delay the expression of antigenic molecules. Our framework presented in this study can be widely used for investigating the nuclear retention of nascent transcripts produced in a transcription burst.