Abstract:
:Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, plays a critical role in the orchestration of immune responses. S1P levels within the mammalian host are tightly regulated, in part through the activity of S1P lyase (S1PL) which catalyses its irreversible degradation. Herein, we describe the identification and characterization of secreted S1PL orthologues encoded by the facultative intracellular bacteria Burkholderia pseudomallei and Burkholderia thailandensis. These bacterial orthologues exhibited S1PL enzymatic activity, functionally complemented an S1PL-deficient yeast strain and conferred resistance to the antimicrobial sphingolipid D-erythro-sphingosine. We report that secretion of these bacterial S1PLs is pH-dependent, and is observed during intracellular infection. S1PL-deficient mutants displayed impaired intracellular replication in murine macrophages (associated with an inability to evade the maturing phagosome) and were significantly attenuated in murine and larval infection models. Furthermore, treatment of Burkholderia-infected macrophages with either S1P or a selective agonist of S1P receptor 1 enhanced bacterial colocalisation with LAMP-1 and reduced their intracellular survival. In summary, our studies confirm bacterial-encoded S1PL as a critical virulence determinant of B. pseudomallei and B. thailandensis, further highlighting the pivotal role of S1P in host-pathogen interactions. In addition, our data suggest that S1P pathway modulators have potential for the treatment of intracellular infection.
journal_name
Mol Microbioljournal_title
Molecular microbiologyauthors
Custódio R,McLean CJ,Scott AE,Lowther J,Kennedy A,Clarke DJ,Campopiano DJ,Sarkar-Tyson M,Brown ARdoi
10.1111/mmi.13531subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1004-1019issue
6eissn
0950-382Xissn
1365-2958journal_volume
102pub_type
杂志文章abstract::F plasmid traY protein binding to wild-type or deleted regions containing the TraY-binding site, sbyA, was studied in vitro. The principal DNA-protein complex was formed with DNA segments including the sbyA site defined by footprinting and (with lesser affinity) with truncated segments that retained the leftward two-t...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.1994.tb00327.x
更新日期:1994-02-01 00:00:00
abstract::Myxococcus xanthus is a Gram-negative bacterium capable of complex developmental processes involving vegetative swarming and fruiting body formation. Social (S-) gliding motility, one of the two motility systems used by M. xanthus, requires at least two cell surface structures: type IV pili (TFP) and extracellular pol...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2010.07180.x
更新日期:2010-06-01 00:00:00
abstract::A gene conferring low-level isoniazid (INH) resistance on Mycobacterium smegmatis was isolated from a cosmid library of the genome of an INH-resistant Mycobacterium bovis strain. The gene had good homology with ahpC, the product of which is a subunit of alkyl hydroperoxide reductase, and also with a family of thiol-sp...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.1996.449980.x
更新日期:1996-03-01 00:00:00
abstract::Mechanisms of hydrogen peroxide generation in Escherichia coli were investigated using a strain lacking scavenging enzymes. Surprisingly, the deletion of many abundant flavoenzymes that are known to autoxidize in vitro did not substantially lessen overall H(2)O(2) formation. However, H(2)O(2) production diminished by ...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2010.07059.x
更新日期:2010-03-01 00:00:00
abstract::Cytochrome c biogenesis describes the posttranslational pathway for the conversion of pre-apocytochrome c into the mature holocytochrome c. It involves an unknown number of consecutive biochemical steps, including translocation of the precursor polypeptide and haem into the periplasm and the covalent linkage between t...
journal_title:Molecular microbiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2958.1994.tb00988.x
更新日期:1994-04-01 00:00:00
abstract::The TonB system of Escherichia coli (TonB/ExbB/ExbD) transduces the protonmotive force (pmf) of the cytoplasmic membrane to drive active transport by high-affinity outer membrane transporters. In this study, chromosomally encoded ExbD formed formaldehyde-linked complexes with TonB, ExbB and itself (homodimers) in vivo...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2009.06785.x
更新日期:2009-08-01 00:00:00
abstract::Interpretation of the constantly expanding body of genomic information requires that the function of each gene be established. Here we report the genomic analysis and structural modelling of a previously uncharacterized redox-metabolism protein UrdA (SO_4620) of Shewanella oneidensis MR-1, which led to a discovery of ...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/mmi.12067
更新日期:2012-12-01 00:00:00
abstract::MarR, the negative regulator of the Escherichia coli multiple antibiotic resistance (marRAB) operon, is a member of a newly recognized family of regulatory proteins. The amino acid sequences of these proteins do not display any apparent homologies to the DNA binding domains of prokaryotic transcription regulators and ...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.2000.01802.x
更新日期:2000-03-01 00:00:00
abstract::The bacterium Burkholderia glumae causes rice grain rot by producing toxoflavin, whose expression is regulated by quorum sensing (QS). We report a major deviation from the current paradigm for the regulation of bacterial polar flagellum genes. The N-octanoyl homoserine lactone (C8-HSL)-deficient mutant of B. glumae is...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2007.05646.x
更新日期:2007-04-01 00:00:00
abstract::We report the identification and functional analysis of katN, a gene encoding a non-haem catalase of Salmonella enterica serotype Typhimurium. katN, which is not present in Escherichia coli, is located between the yciGFE and yciD E. coli homologues in the Salmonella genome. Its predicted protein product has a molecula...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.2001.02340.x
更新日期:2001-03-01 00:00:00
abstract::We have shown previously that some particular mutations in bacteriophage Mu repressor, the frameshift vir mutations, made the protein very sensitive to the Escherichia coli ATP-dependent Clp protease. This enzyme is formed by the association between a protease subunit (ClpP) and an ATPase subunit. ClpA, the best chara...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.1994.tb00387.x
更新日期:1994-03-01 00:00:00
abstract::The tetA(L) gene of Bacillus subtilis encodes a transmembrane protein that can function as a Tc-metal/H+ antiporter, conferring low-level resistance to tetracycline. The TetA(L) coding sequence is preceded by a leader region that contains a 20-amino-acid open reading frame and an appropriately spaced ribosome binding ...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.1998.01119.x
更新日期:1998-12-01 00:00:00
abstract::Copper ions are essential but also very toxic. Copper resistance in bacteria is based on export of the toxic ion, oxidation from Cu(I) to Cu(II), and sequestration by copper-binding metal chaperones, which deliver copper ions to efflux systems or metal-binding sites of copper-requiring proteins. In their publication i...
journal_title:Molecular microbiology
pub_type: 评论,杂志文章
doi:10.1111/mmi.12123
更新日期:2013-02-01 00:00:00
abstract::The endoribonuclease RNase E plays an important role in RNA processing and degradation in Escherichia coli. The construction of an E. coli strain in which the cellular concentration of RNase E can be precisely controlled has made it possible to examine and quantify the effect of RNase E scarcity on RNA decay, gene reg...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.2002.02808.x
更新日期:2002-02-01 00:00:00
abstract::The Bacillus subtilis GlnR transcription factor regulates gene expression in response to changes in nitrogen availability. Glutamine synthetase transmits the nitrogen regulatory signal to GlnR. The DNA-binding activity of GlnR is activated by a transient protein-protein interaction with feedback-inhibited glutamine sy...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2008.06162.x
更新日期:2008-04-01 00:00:00
abstract::Among players in neurobiology, ion channels are the demigods that underlie all our senses, behaviour and intelligence. In animals, these 'gated pores' detect ligands, voltage, heat or stretch forces and emit electric or ionic signals. Patch clamp and genome sequencing now show that nearly all microbes also have these ...
journal_title:Molecular microbiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2958.2004.04180.x
更新日期:2004-07-01 00:00:00
abstract::Cell division in most bacteria is directed by FtsZ, a conserved tubulin-like GTPase that assembles forming the cytokinetic Z-ring and constitutes a target for the discovery of new antibiotics. The developmental regulator MciZ, a 40-amino acid peptide endogenously produced during Bacillus subtilis sporulation, halts cy...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/mmi.14198
更新日期:2019-04-01 00:00:00
abstract::Progress towards understanding the molecular basis of virulence in Clostridium difficile has been hindered by the lack of effective gene transfer systems. We have now, for the first time, developed procedures that may be used to introduce autonomously replicating vectors into this organism through their conjugative, o...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.2002.03134.x
更新日期:2002-10-01 00:00:00
abstract::The identification, isolation and characterization of a new Aspergillus nidulans positive-acting gene metR, which encodes a transcriptional activator of sulphur metabolism, is reported. metR mutants are tight auxotrophs requiring methionine or homocysteine for growth. Mutations in the metR gene are epistatic to mutati...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.2003.03617.x
更新日期:2003-08-01 00:00:00
abstract::Sequence-inherent targeting information directs polypeptides synthesized in the cytosol to their respective cellular compartment. Some proteins use ambiguous sorting signals or specific folding properties to be dually distributed between the cytosol and mitochondria. A study published in this issue of Molecular Microb...
journal_title:Molecular microbiology
pub_type: 评论,杂志文章
doi:10.1111/j.1365-2958.2009.06660.x
更新日期:2009-04-01 00:00:00
abstract::Transmission of Plasmodium species from a mammalian host to the mosquito vector requires the uptake, during an infected blood meal, of gametocytes, the precursor cells of the gametes. Relatively little is known about the molecular mechanisms involved in the developmental switch from asexual development to sexual diffe...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2011.07767.x
更新日期:2011-09-01 00:00:00
abstract::The development of new drugs for treating Pneumocystis carinii infections in AIDS patients is hampered by the lack of long-term culture systems, and by our generally limited knowledge of this organism. Recently, however, we observed significant activity of various benzimidazoles against growth of this organism in shor...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.1992.tb02204.x
更新日期:1992-11-01 00:00:00
abstract::The group A streptococcal emm-like genes, which encode the cell-surface M and M-like proteins, are divided into distinct mrp, emm and enn subdivisions and are clustered together in a region of the chromosome called the vir regulon. In order to understand the mechanisms involved in the evolution of emm-like genes, a 18...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.1995.tb02279.x
更新日期:1995-03-01 00:00:00
abstract::Originally annotated as the initiator of fatty acid synthesis (FAS), β-ketoacyl-acyl carrier protein synthase III (KAS III) is a unique component of the bacterial FAS system. Novel variants of KAS III have been identified that promote the de novo use of additional extracellular fatty acids by FAS. These KAS III varian...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/mmi.13950
更新日期:2018-06-01 00:00:00
abstract::The [NiFe]hydrogenase of the photosynthetic bacterium Rhodobacter capsulatus is encoded by the structural hupSLC operon, the expression of which is induced by H2. H2 activation was no longer observable in chromosomal hupR mutants, an indication that HupR is implicated directly in the activation by H2 of hupS gene expr...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.1997.6291996.x
更新日期:1997-12-01 00:00:00
abstract::ToxR of Vibrio cholerae directly activates the ompU promoter, but requires a second activator, TcpP to activate the toxT promoter. ompU encodes a porin, while toxT encodes the transcription factor, ToxT, which activates V. cholerae virulence genes including cholera toxin and the toxin co-regulated pilus. Using an ompU...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2011.07681.x
更新日期:2011-07-01 00:00:00
abstract::In Escherichia coli, initiation of chromosome replication requires that DnaA binds to R boxes (9-mer repeats) in oriC, the unique chromosomal replication origin. At the time of initiation, integration host factor (IHF) also binds to a specific site in oriC. IHF stimulates open complex formation by DnaA on supercoiled ...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.2000.01755.x
更新日期:2000-02-01 00:00:00
abstract::SecA is the dissociable ATPase subunit of the Escherichia coli preprotein translocase, and cycles in a nucleotide-modulated manner between the cytosol and the membrane. Overproduction of the integral subunits of the translocase, the SecY, SecE and SecG polypeptides, results in an increased level of membrane-bound SecA...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1046/j.1365-2958.1996.d01-1712.x
更新日期:1996-11-01 00:00:00
abstract::Pseudomonas putida WCS358 can transport iron complexed to a wide variety of pseudobactins produced by other Pseudomonas strains. The pupB gene encoding an outer membrane ferric-pseudobactin receptor was isolated from a genomic library of P. putida WCS358. The PupB receptor facilitated iron transport via two distinct h...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.1993.tb01603.x
更新日期:1993-05-01 00:00:00
abstract::Alternaria brassicicola is an important, necrotrophic fungal pathogen that causes black spot disease on Brassicas. In order to study pathogenicity mechanisms, gene deletion mutants were generated for 21 putative regulatory genes including kinases and transcription factors subjectively selected from the annotated A. br...
journal_title:Molecular microbiology
pub_type: 杂志文章
doi:10.1111/j.1365-2958.2009.06689.x
更新日期:2009-06-01 00:00:00