understanding-impact-temperate-bacteriophages-on-their-lysogens

Understanding the Impact of Temperate Bacteriophages on Their Lysogens Through Transcriptomics

Temperate phages are found integrated as prophages in the majority of bacterial genomes. Some prophages are cryptic and fixed in the bacterial chromosome, ...

University of salford

The pathogenicity of Shiga-like toxin (stx)-producing Escherichia coli (STEC), notably serotype O157, the causative agent of hemorrhagic colitis, hemolytic-uremic syndrome, and thrombotic thrombocytopenic purpura, is based partly on the presence of genes (stx(1) and/or stx(2)) that are known to be carried on temperate lambdoid bacteriophages. Stx phages were isolated from different STEC strains and found to have genome sizes in the range of 48 to 62 kb and to carry either stx(1) or stx(2) genes. Restriction fragment length polymorphism patterns and sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles were relatively uninformative, but the phages could be differentiated according to their immunity profiles. Furthermore, these were sufficiently sensitive to enable the identification and differentiation of two different phages, both carrying the genes for Stx2 and originating from the same STEC host strain. The immunity profiles of the different Stx phages did not conform to the model established for bacteriophage lambda, in that the pattern of individual Stx phage infection of various lysogens was neither expected nor predicted. Unexpected differences were also observed among Stx phages in their relative lytic productivity within a single host. Two antibiotic resistance markers were used to tag a recombinant phage in which the stx genes were inactivated, enabling the first reported observation of the simultaneous infection of a single host with two genetically identical Stx phages. The data demonstrate that, although Stx phages are members of the lambdoid family, their replication and infection control strategies are not necessarily identical to the archetypical bacteriophage lambda, and this could be responsible for the widespread occurrence of stx genes across a diverse range of E. coli serotypes.

Immunity profiles of wild-type and recombinant shiga-like toxin-encoding bacteriophages and characterization of novel double lysogens.

Infection of Escherichia coli by Shiga toxin-encoding bacteriophages (Stx phages) was the pivotal event in the evolution of the deadly Shiga toxin-encoding E. coli (STEC), of which serotype O157:H7 is the most notorious. The number of different bacterial species and strains reported to produce Shiga toxin is now more than 500, since the first reported STEC infection outbreak in 1982. Clearly, Stx phages are spreading rapidly, but the underlying mechanism for this dissemination has not been explained. Here we show that an essential and highly conserved gene product, YaeT, which has an essential role in the insertion of proteins in the gram-negative bacterial outer membrane, is the surface molecule recognized by the majority (ca. 70%) of Stx phages via conserved tail spike proteins associated with a short-tailed morphology. The yaeT gene was initially identified through complementation, and its role was confirmed in phage binding assays with and without anti-YaeT antiserum. Heterologous cloning of E. coli yaeT to enable Stx phage adsorption to Erwinia carotovora and the phage adsorption patterns of bacterial species possessing natural yaeT variants further supported this conclusion. The use of an essential and highly conserved protein by the majority of Stx phages is a strategy that has enabled and promoted the rapid spread of shigatoxigenic potential throughout multiple E. coli serogroups and related bacterial species. Infection of commensal bacteria in the mammalian gut has been shown to amplify Shiga toxin production in vivo, and the data from this study provide a platform for the development of a therapeutic strategy to limit this YaeT-mediated infection of the commensal flora.

Short-tailed stx phages exploit the conserved YaeT protein to disseminate Shiga toxin genes among enterobacteria.

Phage production in response to antibiotics varied among four isolates of a Pseudomonas aeruginosa cystic fibrosis (CF) epidemic strain. Whereas ciprofloxacin induced higher levels of phage production, other CF-relevant antibiotics led to reduced production. We detected free phages directly in CF patient sputum samples by both plaque (40% positive) and PCR (76% positive) assays. Our observations suggest that the choice of antibiotics could influence the number of free phages within the CF lung environment.

Effect of antibiotic treatment on bacteriophage production by a cystic fibrosis epidemic strain of Pseudomonas aeruginosa.

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Pseudomonas aeruginosa is a highly successful opportunistic pathogen that displays intrinsic multidrug resistance and has a tremendous capacity to acquire further resistance mechanisms. During chronic infection, the bacterium can form a protective biofilm therefore reducing the efficacy of existing antibiotics. P. aeruginosa also harbors an impressive range of virulence factors, many of which are controlled by the quorum-sensing system. Several novel therapeutics are under investigation such as those directed against biofilm formation and quorum-sensing systems along with bacteriophages and immunotherapies. Recent advances in next-generation sequencing and comparative genomics have opened the door to a new wave of smart drug design that could revolutionize P. aeruginosa treatment options.

Novel therapeutic strategies to counter Pseudomonas aeruginosa infections.

Pseudomonas aeruginosa est un pathog&egrave;ne opportuniste tr&egrave;s r&eacute;ussi qui montre une r&eacute;sistance multidrogue intrins&egrave;que et a une &eacute;norme capacit&eacute; d&#39;acqu&eacute;rir davantage de m&eacute;canismes de r&eacute;sistance. Au cours de l&#39;infection chronique, la bact&eacute;rie peut se former un biofilm protecteur, ce qui r&eacute;duit l&#39;efficacit&eacute; des antibiotiques existants. P. aeruginosa rec&egrave;le &eacute;galement un &eacute;ventail impressionnant de facteurs de virulence, dont beaucoup sont contr&ocirc;l&eacute;s par le syst&egrave;me de quorum-sensing. Plusieurs nouvelles th&eacute;rapeutiques sont incrimin&eacute;s comme ceux dirig&eacute;s contre le biofilm formation et quorum-sensing systems ainsi que les bact&eacute;riophages et d&#39;immunoth&eacute;rapies. Les progr&egrave;s r&eacute;cents dans le s&eacute;quen&ccedil;age de la g&eacute;n&eacute;ration et la g&eacute;nomique comparative ont ouvert la porte &agrave; une nouvelle vague de conception de puce de drogue qui pourrait r&eacute;volutionner les options de traitement de P. aeruginosa.

Nouvelles strat&eacute;gies th&eacute;rapeutiques pour les infections &agrave; Pseudomonas aeruginosa compteur.

Pseudomonas Aeruginosa ist ein h&ouml;chst erfolgreiche opportunistische Erreger, die systeminterne erfolgt mit breiter Widerstand zeigt und hat eine enorme Kapazit&auml;t zur &Uuml;bernahme von weiteren Resistenzmechanismen. W&auml;hrend der chronischen Infektion kann das Bakterium einen sch&uuml;tzenden Biofilm, wodurch die Wirksamkeit der vorhandenen Antibiotika bilden. P. Aeruginosa birgt auch eine beeindruckende Palette von Virulenzfaktoren, von die viele &uuml;ber die Quorum-sensing-System gesteuert werden. Mehrere neuartige Therapeutika werden untersucht z. B. gegen Biofilm Formation und Quorum-sensing Systeme zusammen mit Bakteriophagen und Immuntherapien. J&uuml;ngste Fortschritte in der n&auml;chsten Generation-Sequenzierung und vergleichende Genomik haben die T&uuml;r zu einer neuen Welle der intelligente Wirkstoffdesign ge&ouml;ffnet, die p. Aeruginosa Behandlungsm&ouml;glichkeiten revolutionieren k&ouml;nnte.

Neuartige therapeutische Strategien zur Theke Pseudomonas Aeruginosa-Infektionen.

Pseudomonas aeruginosa &egrave; un patogeno opportunistico altamente riuscito che visualizza intrinseca resistenza di multidrug e ha una tremenda capacit&agrave; di acquisire ulteriori meccanismi di resistenza. Durante l&#39;infezione cronica, il batterio pu&ograve; formare un biofilm protettivo, riducendo l&#39;efficacia degli antibiotici esistenti. P. aeruginosa anche porti un&#39;impressionante gamma di fattori di virulenza, molti dei quali sono controllati dal sistema di quorum sensing. Diverse nuove terapie sono sotto inchiesta come quelli diretti contro il biofilm formazione e sistemi di quorum sensing con batteriofagi e immunoterapie. I recenti progressi nella next-generation sequencing e genomica comparativa hanno aperto le porte a una nuova ondata di smart drug design che potrebbe rivoluzionare le opzioni di trattamento di p. aeruginosa.

Nuove strategie terapeutiche per le infezioni di contatore Pseudomonas aeruginosa.

&#x7DD1;&#x81BF;&#x83CC;&#x306F;&#x7D44;&#x307F;&#x8FBC;&#x307F;&#x306E;&#x591A;&#x5264;&#x8010;&#x6027;&#x3092;&#x8868;&#x793A;&#x3057;&#x3001;&#x3055;&#x3089;&#x306B;&#x62B5;&#x6297;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x3092;&#x53D6;&#x5F97;&#x9014;&#x65B9;&#x3082;&#x306A;&#x3044;&#x80FD;&#x529B;&#x3092;&#x6301;&#x3063;&#x3066;&#x3044;&#x307E;&#x3059;&#x975E;&#x5E38;&#x306B;&#x6210;&#x529F;&#x3057;&#x305F;&#x65E5;&#x548C;&#x898B;&#x75C5;&#x539F;&#x4F53;&#x3067;&#x3059;&#x3002;&#x6162;&#x6027;&#x306E;&#x611F;&#x67D3;&#x4E2D;&#x306B;&#x7D30;&#x83CC;&#x3057;&#x305F;&#x304C;&#x3063;&#x3066;&#x65E2;&#x5B58;&#x306E;&#x6297;&#x751F;&#x7269;&#x8CEA;&#x306E;&#x6709;&#x52B9;&#x6027;&#x3092;&#x6E1B;&#x3089;&#x3059;&#x4FDD;&#x8B77;&#x30D0;&#x30A4;&#x30AA; &#x30D5;&#x30A3;&#x30EB;&#x30E0;&#x3092;&#x5F62;&#x6210;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x7DD1;&#x81BF;&#x83CC;&#x306F;&#x307E;&#x305F;&#x591A;&#x6570;&#x304C;&#x3001;&#x30AF;&#x30AA;&#x30E9;&#x30E0;&#x30BB;&#x30F3;&#x30B7;&#x30F3;&#x30B0; &#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x306B;&#x3088;&#x3063;&#x3066;&#x5236;&#x5FA1;&#x3055;&#x308C;&#x308B;&#x3001;&#x75C5;&#x539F;&#x56E0;&#x5B50;&#x306E;&#x5370;&#x8C61;&#x7684;&#x306A;&#x7BC4;&#x56F2;&#x3092;&#x96A0;&#x3057;&#x6301;&#x3063;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3044;&#x304F;&#x3064;&#x304B;&#x306E;&#x65B0;&#x3057;&#x3044;&#x6CBB;&#x7642;&#x5B66;&#x306E;&#x3042;&#x308B;&#x30D0;&#x30A4;&#x30AA; &#x30D5;&#x30A3;&#x30EB;&#x30E0;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x76E3;&#x7763;&#x306A;&#x3069;&#x306E;&#x8ABF;&#x67FB;&#x306E;&#x4E0B;&#x5F62;&#x6210;&#x3068;&#x30AF;&#x30A9;&#x30FC;&#x30E9;&#x30E0; &#x30BB;&#x30F3;&#x30B7;&#x30F3;&#x30B0; &#x30B7;&#x30B9;&#x30C6;&#x30E0; &#x30D0;&#x30AF;&#x30C6;&#x30EA;&#x30AA;&#x30D5;&#x30A1;&#x30FC;&#x30B8;&#x3068;&#x514D;&#x75AB;&#x7642;&#x6CD5;&#x3068;&#x4E00;&#x7DD2;&#x306B;&#x3002;&#x6B21;&#x4E16;&#x4EE3;&#x30B7;&#x30FC;&#x30B1;&#x30F3;&#x30B7;&#x30F3;&#x30B0;&#x304A;&#x3088;&#x3073;&#x6BD4;&#x8F03;&#x30B2;&#x30CE;&#x30DF;&#x30AF;&#x30B9;&#x306E;&#x6700;&#x8FD1;&#x306E;&#x9032;&#x6B69;&#x306F;&#x7DD1;&#x81BF;&#x83CC;&#x306E;&#x6CBB;&#x7642;&#x306E;&#x9078;&#x629E;&#x80A2;&#x306B;&#x9769;&#x547D;&#x3092;&#x3082;&#x305F;&#x3089;&#x3059;&#x30B9;&#x30DE;&#x30FC;&#x30C8;&#x85AC;&#x5264;&#x8A2D;&#x8A08;&#x306E;&#x65B0;&#x3057;&#x3044;&#x6CE2;&#x3078;&#x306E;&#x6249;&#x3092;&#x958B;&#x3044;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

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&#xB179; &#xB18D; &#xADE0; &#xD558; &#xD45C;&#xC2DC; &#xB0B4;&#xC7A5; multidrug &#xC800;&#xD56D; &#xACE0; &#xC800;&#xD56D; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xB354; &#xC5BB;&#xC73C;&#xB824;&#xACE0; &#xC5C4;&#xCCAD;&#xB09C; &#xC6A9;&#xB7C9;&#xC774; &#xB9E4;&#xC6B0; &#xC131;&#xACF5;&#xC801;&#xC778; &#xAE30;&#xD68C; &#xBCD1;&#xC6D0; &#xCCB4; &#xC774;&#xB2E4;. &#xB9CC;&#xC131; &#xAC10;&#xC5FC; &#xC2DC; &#xC138;&#xADE0; &#xBCF4;&#xD638; biofilm &#xB530;&#xB77C;&#xC11C; &#xAE30;&#xC874; &#xD56D;&#xC0DD;&#xC81C;&#xC758; &#xD6A8;&#xB2A5;&#xC744; &#xAC10;&#xC18C;&#xB97C; &#xD615;&#xC131;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. P. &#xB18D; &#xADE0;&#xB3C4; &#xB2E4;&#xC591; &#xD55C; &#xB3C5;&#xC131; &#xC694;&#xC778;, &#xCFFC;&#xB7FC; &#xC13C; &#xC2F1; &#xC2DC;&#xC2A4;&#xD15C;&#xC5D0; &#xC758;&#xD574; &#xC81C;&#xC5B4; &#xB418;&#xB294; &#xB9CE;&#xC740; &#xD56D;&#xB9CC;. &#xBA87; &#xAC00;&#xC9C0; &#xC0C8;&#xB85C;&#xC6B4; &#xCE58;&#xB8CC; &#xD559; biofilm&#xC5D0; &#xB300; &#xD55C; &#xAC10;&#xB3C5; &#xB4F1; &#xC870;&#xC0AC;&#xB97C; &#xBC1B;&#xACE0; &#xC788;&#xB2E4; &#xD615;&#xC131; &#xBC0F; &#xCFFC;&#xB7FC; &#xC13C; &#xC2F1; &#xC2DC;&#xC2A4;&#xD15C; bacteriophages &#xBC0F; immunotherapies. &#xCC28;&#xC138;&#xB300; &#xC2DC;&#xD000;&#xC2F1; &#xBC0F; &#xBE44;&#xAD50; &#xC720;&#xC804;&#xCCB4;&#xD559;&#xC758; &#xCD5C;&#xADFC; &#xBC1C;&#xC804; P. &#xB18D; &#xADE0; &#xCE58;&#xB8CC; &#xBC29;&#xBC95;&#xC5D0; &#xD601;&#xBA85;&#xC744; &#xC77C;&#xC73C;&#xD0AC; &#xC218; &#xC788;&#xB294; &#xC2A4;&#xB9C8;&#xD2B8; &#xC57D;&#xBB3C; &#xB514;&#xC790;&#xC778;&#xC758; &#xC0C8;&#xB85C;&#xC6B4; &#xBB3C;&#xACB0;&#xC5D0; &#xBB38;&#xC744; &#xC5F4;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xCE74;&#xC6B4;&#xD130; &#xB179; &#xB18D; &#xADE0; &#xAC10;&#xC5FC;&#xC5D0; &#xC0C8;&#xB85C;&#xC6B4; &#xCE58;&#xB8CC; &#xC804;&#xB7B5;&#xC785;&#xB2C8;&#xB2E4;.

Pseudomonas aeruginosa es un pat&oacute;geno oportunista exitoso que muestra la multirresistencia intr&iacute;nseca y tiene una enorme capacidad para adquirir otros mecanismos de resistencia. Durante la infecci&oacute;n cr&oacute;nica, la bacteria puede formar un biofilm protector, por lo tanto reduciendo la eficacia de los antibi&oacute;ticos existentes. P. aeruginosa tambi&eacute;n alberga una impresionante gama de factores de virulencia, muchos de los cuales son controlados por el sistema de detecci&oacute;n de qu&oacute;rum. Varias terapias novedosas est&aacute;n bajo investigaci&oacute;n como las que se dirigen contra el biofilm formaci&oacute;n y sistemas de detecci&oacute;n de qu&oacute;rum junto con bacteri&oacute;fagos e inmunoterapias. Avances recientes en la secuencia de pr&oacute;xima generaci&oacute;n y gen&oacute;mica comparativa han abierto la puerta a una nueva ola de dise&ntilde;o inteligente de medicamentos que podr&iacute;a revolucionar los tratamientos de p. aeruginosa.

Article	Year
Immunity profiles of wild-type and recombinant shiga-like toxin-encoding bacteriophages and characterization of novel double lysogens. Infection and immunity\| PubMed ID: 12761125	2003
FEMS microbiology letters\| PubMed ID: 15837394	2005
Molecular microbiology\| PubMed ID: 16556225	2006
Infection and immunity\| PubMed ID: 16790755	2006
Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 16832066	2006
FEMS microbiology letters\| PubMed ID: 16907740	2006
Cellular microbiology\| PubMed ID: 17419719	2007
Antimicrobial agents and chemotherapy\| PubMed ID: 17606680	2007
Short-tailed stx phages exploit the conserved YaeT protein to disseminate Shiga toxin genes among enterobacteria. Journal of bacteriology\| PubMed ID: 17693515	2007
Current drug targets\| PubMed ID: 18781921	2008
Nature reviews. Microbiology\| PubMed ID: 18997824	2008
PloS one\| PubMed ID: 19434239	2009
Pharmacogenetics and genomics\| PubMed ID: 20051929	2010
Effect of antibiotic treatment on bacteriophage production by a cystic fibrosis epidemic strain of Pseudomonas aeruginosa. Antimicrobial agents and chemotherapy\| PubMed ID: 20974862	2011
Novel therapeutic strategies to counter Pseudomonas aeruginosa infections. Expert review of anti-infective therapy\| PubMed ID: 22339195	2012

Chloë E. James

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