A quorum sensing regulated small volatile molecule reduces acute virulence and promotes chronic infection phenotypes.

Abstract:

:A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals that contribute to a successful acute infection have been identified in a number of pathogens, the signals that mediate the onset and establishment of chronic infections have yet to be discovered. We identified a volatile, low molecular weight molecule, 2-amino acetophenone (2-AA), produced by the opportunistic human pathogen Pseudomonas aeruginosa that reduces bacterial virulence in vivo in flies and in an acute mouse infection model. 2-AA modulates the activity of the virulence regulator MvfR (multiple virulence factor regulator) via a negative feedback loop and it promotes the emergence of P. aeruginosa phenotypes that likely promote chronic lung infections, including accumulation of lasR mutants, long-term survival at stationary phase, and persistence in a Drosophila infection model. We report for the first time the existence of a quorum sensing (QS) regulated volatile molecule that induces bistability phenotype by stochastically silencing acute virulence functions in P. aeruginosa. We propose that 2-AA mediates changes in a subpopulation of cells that facilitate the exploitation of dynamic host environments and promote gene expression changes that favor chronic infections.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Kesarwani M,Hazan R,He J,Que YA,Apidianakis Y,Lesic B,Xiao G,Dekimpe V,Milot S,Deziel E,Lépine F,Rahme LG

doi

10.1371/journal.ppat.1002192

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

e1002192

issue

8

eissn

1553-7366

issn

1553-7374

pii

11-PLPA-RA-4256

journal_volume

7

pub_type

杂志文章
  • The herpes virus Fc receptor gE-gI mediates antibody bipolar bridging to clear viral antigens from the cell surface.

    abstract::The Herpes Simplex Virus 1 (HSV-1) glycoprotein gE-gI is a transmembrane Fc receptor found on the surface of infected cells and virions that binds human immunoglobulin G (hIgG). gE-gI can also participate in antibody bipolar bridging (ABB), a process by which the antigen-binding fragments (Fabs) of the IgG bind a vira...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003961

    authors: Ndjamen B,Farley AH,Lee T,Fraser SE,Bjorkman PJ

    更新日期:2014-03-06 00:00:00

  • Analysis of the SUMO2 Proteome during HSV-1 Infection.

    abstract::Covalent linkage to members of the small ubiquitin-like (SUMO) family of proteins is an important mechanism by which the functions of many cellular proteins are regulated. Sumoylation has roles in the control of protein stability, activity and localization, and is involved in the regulation of transcription, gene expr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005059

    authors: Sloan E,Tatham MH,Groslambert M,Glass M,Orr A,Hay RT,Everett RD

    更新日期:2015-07-22 00:00:00

  • Cross-serotype immunity induced by immunization with a conserved rhinovirus capsid protein.

    abstract::Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broa...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003669

    authors: Glanville N,McLean GR,Guy B,Lecouturier V,Berry C,Girerd Y,Gregoire C,Walton RP,Pearson RM,Kebadze T,Burdin N,Bartlett NW,Almond JW,Johnston SL

    更新日期:2013-01-01 00:00:00

  • Gain-of-sensitivity mutations in a Trim5-resistant primary isolate of pathogenic SIV identify two independent conserved determinants of Trim5α specificity.

    abstract::Retroviral capsid recognition by Trim5 blocks productive infection. Rhesus macaques harbor three functionally distinct Trim5 alleles: Trim5α(Q) , Trim5α(TFP) and Trim5(CypA) . Despite the high degree of amino acid identity between Trim5α(Q) and Trim5α(TFP) alleles, the Q/TFP polymorphism results in the differential re...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003352

    authors: McCarthy KR,Schmidt AG,Kirmaier A,Wyand AL,Newman RM,Johnson WE

    更新日期:2013-05-01 00:00:00

  • Mobile genetic element SCCmec-encoded psm-mec RNA suppresses translation of agrA and attenuates MRSA virulence.

    abstract::Community acquired-methicillin resistant Staphylococcus aureus (CA-MRSA) is a socially problematic pathogen that infects healthy individuals, causing severe disease. CA-MRSA is more virulent than hospital associated-MRSA (HA-MRSA). The underlying mechanism for the high virulence of CA-MRSA is not known. The transcript...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003269

    authors: Kaito C,Saito Y,Ikuo M,Omae Y,Mao H,Nagano G,Fujiyuki T,Numata S,Han X,Obata K,Hasegawa S,Yamaguchi H,Inokuchi K,Ito T,Hiramatsu K,Sekimizu K

    更新日期:2013-01-01 00:00:00

  • Dual microRNA Screens Reveal That the Immune-Responsive miR-181 Promotes Henipavirus Entry and Cell-Cell Fusion.

    abstract::Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005974

    authors: Foo CH,Rootes CL,Cowley K,Marsh GA,Gould CM,Deffrasnes C,Cowled CJ,Klein R,Riddell SJ,Middleton D,Simpson KJ,Wang LF,Bean AG,Stewart CR

    更新日期:2016-10-26 00:00:00

  • Horizontal versus familial transmission of Helicobacter pylori.

    abstract::Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000180

    authors: Schwarz S,Morelli G,Kusecek B,Manica A,Balloux F,Owen RJ,Graham DY,van der Merwe S,Achtman M,Suerbaum S

    更新日期:2008-10-01 00:00:00

  • The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome.

    abstract::In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic el...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,随机对照试验

    doi:10.1371/journal.ppat.1006966

    authors: Azarian T,Grant LR,Arnold BJ,Hammitt LL,Reid R,Santosham M,Weatherholtz R,Goklish N,Thompson CM,Bentley SD,O'Brien KL,Hanage WP,Lipsitch M

    更新日期:2018-04-04 00:00:00

  • Antagonism of miR-328 increases the antimicrobial function of macrophages and neutrophils and rapid clearance of non-typeable Haemophilus influenzae (NTHi) from infected lung.

    abstract::Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-micro...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004549

    authors: Tay HL,Kaiko GE,Plank M,Li J,Maltby S,Essilfie AT,Jarnicki A,Yang M,Mattes J,Hansbro PM,Foster PS

    更新日期:2015-04-20 00:00:00

  • Unique biofilm signature, drug susceptibility and decreased virulence in Drosophila through the Pseudomonas aeruginosa two-component system PprAB.

    abstract::Bacterial biofilm is considered as a particular lifestyle helping cells to survive hostile environments triggered by a variety of signals sensed and integrated through adequate regulatory pathways. Pseudomonas aeruginosa, a Gram-negative bacterium causing severe infections in humans, forms biofilms and is a fantastic ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003052

    authors: de Bentzmann S,Giraud C,Bernard CS,Calderon V,Ewald F,Plésiat P,Nguyen C,Grunwald D,Attree I,Jeannot K,Fauvarque MO,Bordi C

    更新日期:2012-01-01 00:00:00

  • A Miniaturized Screen of a Schistosoma mansoni Serotonergic G Protein-Coupled Receptor Identifies Novel Classes of Parasite-Selective Inhibitors.

    abstract::Schistosomiasis is a tropical parasitic disease afflicting ~200 million people worldwide and current therapy depends on a single drug (praziquantel) which exhibits several non-optimal features. These shortcomings underpin the need for next generation anthelmintics, but the process of validating physiologically relevan...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005651

    authors: Chan JD,McCorvy JD,Acharya S,Johns ME,Day TA,Roth BL,Marchant JS

    更新日期:2016-05-17 00:00:00

  • Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli.

    abstract::Toxin-antitoxin (TA) systems are prevalent in many bacterial genomes and have been implicated in biofilm and persister cell formation, but the contribution of individual chromosomally encoded TA systems during bacterial pathogenesis is not well understood. Of the known TA systems encoded by Escherichia coli, only a su...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002954

    authors: Norton JP,Mulvey MA

    更新日期:2012-01-01 00:00:00

  • Viral and cellular proteins containing FGDF motifs bind G3BP to block stress granule formation.

    abstract::The Ras-GAP SH3 domain-binding proteins (G3BP) are essential regulators of the formation of stress granules (SG), cytosolic aggregates of proteins and RNA that are induced upon cellular stress, such as virus infection. Many viruses, including Semliki Forest virus (SFV), block SG induction by targeting G3BP. In this wo...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004659

    authors: Panas MD,Schulte T,Thaa B,Sandalova T,Kedersha N,Achour A,McInerney GM

    更新日期:2015-02-06 00:00:00

  • A complex extracellular sphingomyelinase of Pseudomonas aeruginosa inhibits angiogenesis by selective cytotoxicity to endothelial cells.

    abstract::The hemolytic phospholipase C (PlcHR) expressed by Pseudomonas aeruginosa is the original member of a Phosphoesterase Superfamily, which includes phosphorylcholine-specific phospholipases C (PC-PLC) produced by frank and opportunistic pathogens. PlcHR, but not all its family members, is also a potent sphingomyelinase ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000420

    authors: Vasil ML,Stonehouse MJ,Vasil AI,Wadsworth SJ,Goldfine H,Bolcome RE 3rd,Chan J

    更新日期:2009-05-01 00:00:00

  • Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells.

    abstract::HIV and other lentiviruses can productively infect nondividing cells, whereas most other retroviruses, such as murine leukemia virus, require cell division for efficient infection. However, the determinants for this phenotype have been controversial. Here, we show that HIV-1 capsid (CA) is involved in facilitating HIV...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030156

    authors: Yamashita M,Perez O,Hope TJ,Emerman M

    更新日期:2007-10-26 00:00:00

  • A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape.

    abstract::Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-β-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is mediated by am...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001072

    authors: Agudo R,Ferrer-Orta C,Arias A,de la Higuera I,Perales C,Pérez-Luque R,Verdaguer N,Domingo E

    更新日期:2010-08-26 00:00:00

  • Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction.

    abstract::Although invasive cytomegalovirus (CMV) disease is uncommon in the era of antiretroviral therapy (ART), asymptomatic CMV coinfection is nearly ubiquitous in HIV infected individuals. While microbial translocation and gut epithelial barrier dysfunction may promote persistent immune activation in treated HIV infection, ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006202

    authors: Maidji E,Somsouk M,Rivera JM,Hunt PW,Stoddart CA

    更新日期:2017-02-27 00:00:00

  • Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.

    abstract::Vibrio cholerae has evolved to adeptly transition between the human small intestine and aquatic environments, leading to water-borne spread and transmission of the lethal diarrheal disease cholera. Using a host model that mimics the pathology of human cholera, we applied high density transposon mutagenesis combined wi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003800

    authors: Kamp HD,Patimalla-Dipali B,Lazinski DW,Wallace-Gadsden F,Camilli A

    更新日期:2013-01-01 00:00:00

  • Identification of adipocyte plasma membrane-associated protein as a novel modulator of human cytomegalovirus infection.

    abstract::Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause disability in newborns and serious clinical diseases in immunocompromised patients. HCMV has a large genome with enormous coding potential; its viral particles are equipped with complicated glycoprotein complexes and can infect a wide range of human ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007914

    authors: Ye X,Gui X,Freed DC,Ku Z,Li L,Chen Y,Xiong W,Fan X,Su H,He X,Rustandi RR,Loughney JW,Ma N,Espeseth AS,Liu J,Zhu H,Wang D,Zhang N,Fu TM,An Z

    更新日期:2019-07-29 00:00:00

  • HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2- and CCL5- mediated recruitment of mast cells.

    abstract::Human Papillomavirus (HPV) 16 E7 protein promotes the transformation of HPV infected epithelium to malignancy. Here, we use a murine model in which the E7 protein of HPV16 is expressed as a transgene in epithelium to show that mast cells are recruited to the basal layer of E7-expressing epithelium, and that this recru...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004466

    authors: Bergot AS,Ford N,Leggatt GR,Wells JW,Frazer IH,Grimbaldeston MA

    更新日期:2014-10-23 00:00:00

  • A conserved NS3 surface patch orchestrates NS2 protease stimulation, NS5A hyperphosphorylation and HCV genome replication.

    abstract::Hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide. The HCV RNA genome is translated into a single polyprotein. Most of the cleavage sites in the non-structural (NS) polyprotein region are processed by the NS3/NS4A serine protease. The vital NS2-NS3 cleavage is catalyzed by the NS2 autopro...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004736

    authors: Isken O,Langerwisch U,Jirasko V,Rehders D,Redecke L,Ramanathan H,Lindenbach BD,Bartenschlager R,Tautz N

    更新日期:2015-03-16 00:00:00

  • Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection.

    abstract::The MHC class I D(k) molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds D(k), are required to control viral spread. The extent of D(k)-dependent host resistance, however, differs significa...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005419

    authors: Gillespie AL,Teoh J,Lee H,Prince J,Stadnisky MD,Anderson M,Nash W,Rival C,Wei H,Gamache A,Farber CR,Tung K,Brown MG

    更新日期:2016-02-04 00:00:00

  • Multiple translocation of the AVR-Pita effector gene among chromosomes of the rice blast fungus Magnaporthe oryzae and related species.

    abstract::Magnaporthe oryzae is the causal agent of rice blast disease, a devastating problem worldwide. This fungus has caused breakdown of resistance conferred by newly developed commercial cultivars. To address how the rice blast fungus adapts itself to new resistance genes so quickly, we examined chromosomal locations of AV...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002147

    authors: Chuma I,Isobe C,Hotta Y,Ibaragi K,Futamata N,Kusaba M,Yoshida K,Terauchi R,Fujita Y,Nakayashiki H,Valent B,Tosa Y

    更新日期:2011-07-01 00:00:00

  • Rapid pathogen-induced apoptosis: a mechanism used by dendritic cells to limit intracellular replication of Legionella pneumophila.

    abstract::Dendritic cells (DCs) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites, and then migrate to lymphatic organs to display foreign peptides to naïve T cells. There are several examples where DCs have been shown to be more efficient at restricting the intracellular replicatio...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000478

    authors: Nogueira CV,Lindsten T,Jamieson AM,Case CL,Shin S,Thompson CB,Roy CR

    更新日期:2009-06-01 00:00:00

  • Retention and loss of RNA interference pathways in trypanosomatid protozoans.

    abstract::RNA interference (RNAi) pathways are widespread in metaozoans but the genes required show variable occurrence or activity in eukaryotic microbes, including many pathogens. While some Leishmania lack RNAi activity and Argonaute or Dicer genes, we show that Leishmania braziliensis and other species within the Leishmania...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001161

    authors: Lye LF,Owens K,Shi H,Murta SM,Vieira AC,Turco SJ,Tschudi C,Ullu E,Beverley SM

    更新日期:2010-10-28 00:00:00

  • Dengue Virus Nonstructural Protein 5 (NS5) Assembles into a Dimer with a Unique Methyltransferase and Polymerase Interface.

    abstract::Flavivirus nonstructural protein 5 (NS5) consists of methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, which catalyze 5'-RNA capping/methylation and RNA synthesis, respectively, during viral genome replication. Although the crystal structure of flavivirus NS5 is known, no data about the quater...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005451

    authors: Klema VJ,Ye M,Hindupur A,Teramoto T,Gottipati K,Padmanabhan R,Choi KH

    更新日期:2016-02-19 00:00:00

  • Utilising animal models to evaluate oseltamivir efficacy against influenza A and B viruses with reduced in vitro susceptibility.

    abstract::The neuraminidase (NA) inhibitor (NAI) oseltamivir (OST) is the most widely used influenza antiviral drug. Several NA amino acid substitutions are reported to reduce viral susceptibility to OST in in vitro assays. However, whether there is a correlation between the level of reduction in susceptibility in vitro and the...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008592

    authors: Farrukee R,Tai CM,Oh DY,Anderson DE,Gunalan V,Hibberd M,Lau GY,Barr IG,Messling VV,Maurer-Stroh S,Hurt AC

    更新日期:2020-06-18 00:00:00

  • Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid.

    abstract::The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a pau...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005981

    authors: Ball NJ,Nicastro G,Dutta M,Pollard DJ,Goldstone DC,Sanz-Ramos M,Ramos A,Müllers E,Stirnnagel K,Stanke N,Lindemann D,Stoye JP,Taylor WR,Rosenthal PB,Taylor IA

    更新日期:2016-11-09 00:00:00

  • Irf8-regulated genomic responses drive pathological inflammation during cerebral malaria.

    abstract::Interferon Regulatory Factor 8 (IRF8) is required for development, maturation and expression of anti-microbial defenses of myeloid cells. BXH2 mice harbor a severely hypomorphic allele at Irf8 (Irf8(R294C)) that causes susceptibility to infection with intracellular pathogens including Mycobacterium tuberculosis. We re...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003491

    authors: Berghout J,Langlais D,Radovanovic I,Tam M,MacMicking JD,Stevenson MM,Gros P

    更新日期:2013-01-01 00:00:00

  • Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the cell surface.

    abstract::Helicobacter pylori (Hp) injects the CagA effector protein into host epithelial cells and induces growth factor-like signaling, perturbs cell-cell junctions, and alters host cell polarity. This enables Hp to grow as microcolonies adhered to the host cell surface even in conditions that do not support growth of free-sw...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002050

    authors: Tan S,Noto JM,Romero-Gallo J,Peek RM Jr,Amieva MR

    更新日期:2011-05-01 00:00:00