Elsevier

Plasmid

Volume 80, July 2015, Pages 32-44
Plasmid

Nucleoid-associated proteins encoded on plasmids: Occurrence and mode of function

https://doi.org/10.1016/j.plasmid.2015.04.008Get rights and content

Highlights

  • Nucleoid-associated proteins (NAPs) are global transcriptional regulators in microbial cells.

  • Several NAPs (H-NS family proteins, FIS, HU, IHF, Lrp, and NdpA) are found on plasmids.

  • NAP genes are more frequently found in transferable plasmids.

  • Plasmid-borne H-NS family proteins can reduce the host fitness change.

  • NAP genes play key roles in the integration of plasmids into the host cell.

Abstract

Nucleoid-associated proteins (NAPs) play a role in changing the shape of microbial DNA, making it more compact and affecting the regulation of transcriptional networks in host cells. Genes that encode NAPs include H-NS family proteins (H-NS, Ler, MvaT, BpH3, Bv3F, HvrA, and Lsr2), FIS, HU, IHF, Lrp, and NdpA, and are found in both microbial chromosomes and plasmid DNA. In the present study, NAP genes were distributed among 442 plasmids out of 4602 plasmid sequences, and many H-NS family proteins, and HU, IHF, Lrp, and NdpA were found in plasmids of Alpha-, Beta-, and Gammaproteobacteria, while HvrA, Lsr2, HU, and Lrp were found in other classes including Actinobacteria and Bacilli. Larger plasmids frequently carried multiple NAP genes. In addition, NAP genes were more frequently found in conjugative plasmids than non-transmissible plasmids. Several host cells carried the same types of H-NS family proteins on both their plasmids and chromosome(s), while this was not observed for other NAPs. Recent studies have shown that NAP genes on plasmids and chromosomes play important roles in the physical and regulatory integration of plasmids into the host cell.

Introduction

Plasmids (extrachromosomal replicons) are one of the most important ‘vehicles’ of genes for resistance to antibiotics, metabolism of natural and synthetic compounds, pathogenicity, and host symbiosis. Plasmid transfer is involved in the rapid evolution and adaptation of microbes by transferring specific traits among different host microbes. After a host cell receives a plasmid, integration of the newly acquired genetic elements into the host cell (the successful survival of a plasmid in a host cell) is required to maintain host cell fitness. Several studies have shown that carrying a plasmid is a ‘burden’ on the host because the replication and maintenance of plasmids perturbs host transcriptional networks (Nojiri, 2013, Shintani, 2014). Two mechanisms of plasmid integration into host cells have been described as ‘physical integration’ and ‘regulatory integration’ (Dorman, 2014).

Over the last 10 years, nucleoid-associated proteins (NAPs) have been shown to be involved in folding chromosomal DNA to make it more compact through their DNA-binding ability, which is important for the regulation of transcriptional networks in hosts (Dillon, Dorman, 2010, Nojiri, 2012). One of the best studied NAPs is histone-like nucleoid structuring protein (H-NS) in enterobacteria. Other NAPs have been identified, including factor for inversion stimulation (FIS), histone-like protein from Escherichia coli strain U93 (HU), integration host factor (IHF), and leucine-responsive regulatory protein (Lrp) (Dillon and Dorman, 2010). NdpA (sometimes named YejK in E. coli) is a functionally unknown NAP included in the nucleoid of E. coli and Pseudomonas aeruginosa (Murphy, 1999, Ohniwa, 2011). Some of these NAP genes have been found on plasmids and are thought to play an important role in the integration and adaptation of plasmids into new host cells (Takeda et al., 2011). Recently, Dorman (2014) suggested that NAPs can be used to reduce fitness costs through physical and regulatory integration of plasmids into host cells. In the present study, the distributions of NAP genes on plasmids and their host chromosome(s) were determined as a follow-up to our previous study (Takeda et al., 2011). Recent studies on NAP genes found in plasmids and their (putative) roles in host cells are described.

Section snippets

H-NS family proteins

H-NS, one of the best-characterized NAPs, was shown in the 1970s to be a heat-resistant protein that activates transcription in bacterial cells, and was ‘re-discovered’ as a histone-like protein in bacteria 10 years later (Lammi, 1984, Navarre, 2010). A large number of excellent reviews are available (Dorman, 2004, Dorman, 2014, Fang, Rimsky, 2008, Navarre, 2010, Stoebel, 2008). H-NS is found in the genera Escherichia and Salmonella, whose amino acid sequences show 95% identity. It is one of

Method used to analyze the distribution of NAP genes in genomes

We previously determined the distributions of NAP genes on plasmids and chromosomes (Takeda et al., 2011). Amino acid sequences of H-NS family proteins (H-NS, Ler, MvaT, BpH3, Bv3F, HvrA, Lsr2, XrvA, and Rok) and other NAPs (FIS, HU, IHF, Lrp, and NdpA) were used; their accession numbers in the DDBJ/EMBL/GenBank databases are provided in Table 1. Complete sequences of 4602 plasmids (plasmid database) listed in GenBank (Aug. 2014) and 3279 complete genome sequences of bacteria (genome database,

Functional analyses of NAPs encoded on plasmids

Most reports of NAPs encoded on plasmids have focused on H-NS family proteins, and there are no reports exploring the function of other NAPs encoded on plasmids except for our recent report (Suzuki-Minakuchi et al., 2015). Recent studies that included functional analyses of H-NS family proteins encoded on the plasmids of Enterobacteriaceae and Pseudomonas are described will be discussed later.

Concluding remarks

The present study focused on the roles of NAPs encoded on plasmids and their relationships with those in host chromosomes. H-NS family proteins are thought to be major factors for plasmid integration into host cells. Other NAPs are thought to be important for plasmid replication, maintenance, and transfer. There were many plasmids on which NAP genes were not found, despite their large size and high GC content (Fig. 2). There may be more unidentified NAP genes on plasmids such as H-NSIncA/C, and

Acknowledgments

This work was partially supported by JSPS KAKENHI grant number 24780087 to M.S. and 24380043 to H.N.

References (116)

  • C.J. Dorman

    H-NS-like nucleoid-associated proteins, mobile genetic elements and horizontal gene transfer in bacteria

    Plasmid

    (2014)
  • FangF.C. et al.

    New insights into transcriptional regulation by H-NS

    Curr. Opin. Microbiol

    (2008)
  • C. Fernandez-de-Alba

    On the origin of the selectivity of plasmidic H-NS towards horizontally acquired DNA: linking H-NS oligomerization and cooperative DNA binding

    J. Mol. Biol

    (2013)
  • S.P. Hung

    Global gene expression profiling in Escherichia coli K12. The effects of leucine-responsive regulatory protein

    J. Biol. Chem

    (2002)
  • W. Loftie-Eaton et al.

    Diversity, biology and evolution of IncQ-family plasmids

    Plasmid

    (2012)
  • M.S. Luijsterburg

    The architectural role of nucleoid-associated proteins in the organization of bacterial chromatin: a molecular perspective

    J. Struct. Biol

    (2006)
  • K. Maeda

    Complete nucleotide sequence of carbazole/dioxin-degrading plasmid pCAR1 in Pseudomonas resinovorans strain CA10 indicates its mosaicity and the presence of large catabolic transposon Tn4676

    J. Mol. Biol

    (2003)
  • H. Nojiri

    Impact of catabolic plasmids on host cell physiology

    Curr. Opin. Biotechnol

    (2013)
  • V. Pinson

    Differential binding of the Escherichia coli HU, homodimeric forms and heterodimeric form to linear, gapped and cruciform DNA

    J. Mol. Biol

    (1999)
  • S. Rimsky

    Structure of the histone-like protein H-NS and its role in regulation and genome superstructure

    Curr. Opin. Microbiol

    (2004)
  • D. Skoko

    Mechanism of chromosome compaction and looping by the Escherichia coli nucleoid protein Fis

    J. Mol. Biol

    (2006)
  • K.K. Swinger et al.

    IHF and HU: flexible architects of bent DNA

    Curr. Opin. Struct. Biol

    (2004)
  • M. Adamczyk et al.

    Spread and survival of promiscuous IncP-1 plasmids

    Acta Biochim. Pol

    (2003)
  • T.A. Azam

    Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid

    J. Bacteriol

    (1999)
  • S. Aznar

    The Hha protein facilitates incorporation of horizontally acquired DNA in enteric bacteria

    Microbiology

    (2013)
  • R.C. Baños

    Differential regulation of horizontally acquired and core genome genes by the bacterial modulator H-NS

    PLoS Genet

    (2009)
  • C. Beloin

    Shigella flexneri 2a strain 2457T expresses three members of the H-NS-like protein family: characterization of the Sfh protein

    Mol. Genet. Genomics

    (2003)
  • P. Bertin

    The structural and functional organization of H-NS-like proteins is evolutionarily conserved in gram-negative bacteria

    Mol. Microbiol

    (1999)
  • E. Bouffartigues

    H-NS cooperative binding to high-affinity sites in a regulatory element results in transcriptional silencing

    Nat. Struct. Mol. Biol

    (2007)
  • M.D. Bradley

    Effects of Fis on Escherichia coli gene expression during different growth stages

    Microbiology

    (2007)
  • A.D. Cameron et al.

    A fundamental regulatory mechanism operating through OmpR and DNA topology controls expression of Salmonella pathogenicity islands SPI-1 and SPI-2

    PLoS Genet

    (2012)
  • A. Carattoli

    Resistance plasmid families in Enterobacteriaceae

    Antimicrob. Agents Chemother

    (2009)
  • S. Castang

    H-NS family members function coordinately in an opportunistic pathogen

    Proc. Natl. Acad. Sci. U.S.A.

    (2008)
  • B.K. Cho

    Genome-scale reconstruction of the Lrp regulatory network in Escherichia coli

    Proc. Natl. Acad. Sci. U.S.A.

    (2008)
  • B.K. Cho

    Genome-wide analysis of Fis binding in Escherichia coli indicates a causative role for A-/AT-tracts

    Genome Res

    (2008)
  • S. Chodavarapu

    Escherichia coli DnaA interacts with HU in initiation at the E. coli replication origin

    Mol. Microbiol

    (2008)
  • CuiY.

    A consensus sequence for binding of Lrp to DNA

    J. Bacteriol

    (1995)
  • R.T. Dame

    DNA bridging: a property shared among H-NS-like proteins

    J. Bacteriol

    (2005)
  • P. Deighan

    Three-way interactions among the Sfh, StpA and H-NS nucleoid-structuring proteins of Shigella flexneri 2a strain 2457T

    Mol. Microbiol

    (2003)
  • S.P. Diggle

    Advancing the qorum in Pseudomonas aeruginosa: MvaT and the rgulation of N-acylhomoserine lactone production and virulence gene expression

    J. Bacteriol

    (2002)
  • S.C. Dillon et al.

    Bacterial nucleoid-associated proteins, nucleoid structure and gene expression

    Nat. Rev. Microbiol

    (2010)
  • S.C. Dillon et al.

    Genome-wide analysis of the H-NS and Sfh regulatory networks in Salmonella Typhimurium identifies a plasmid-encoded transcription silencing mechanism

    Mol. Microbiol

    (2010)
  • M.D. Ditto

    Growth phase variation of integration host factor level in Escherichia coli

    J. Bacteriol

    (1994)
  • C.J. Dorman

    H-NS: a universal regulator for a dynamic genome

    Nat. Rev. Microbiol

    (2004)
  • C.J. Dorman

    Regulation of transcription by DNA supercoiling in Mycoplasma genitalium: global control in the smallest known self-replicating genome

    Mol. Microbiol

    (2011)
  • M. Doyle et al.

    Reciprocal transcriptional and posttranscriptional growth-phase-dependent expression of sfh, a gene that encodes a paralogue of the nucleoid-associated protein H-NS

    J. Bacteriol

    (2006)
  • M. Doyle

    An H-NS-like stealth protein aids horizontal DNA transmission in bacteria

    Science

    (2007)
  • S.J. Elliott

    The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli

    Infect. Immun

    (2000)
  • M. Falconi

    Proteins from the prokaryotic nucleoid: primary and quaternary structure of the 15-kD Escherichia coli DNA binding protein H-NS

    Mol. Microbiol

    (1988)
  • FengJ.X.

    The xrvA gene of Xanthomonas oryzae pv. oryzae, encoding an H-NS-like protein, regulates virulence in rice

    Microbiology

    (2009)
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