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Your search keyword '"Hancock, SJ"' showing total 3 results
Start Over Author "Hancock, SJ" Publisher nature pub. group
3 results on '"Hancock, SJ"'

1. A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria.

Author

Nhu NTK, Rahman MA, Goh KGK, Kim SJ, Phan MD, Peters KM, Alvarez-Fraga L, Hancock SJ, Ravi C, Kidd TJ, Sullivan MJ, Irvine KM, Beatson SA, Sweet MJ, Irwin AD, Vukovic J, Ulett GC, Hasnain SZ, and Schembri MA

Subjects
Mice, Animals, Rats, Humans, Virulence genetics, Escherichia coli metabolism, Virulence Factors genetics, Phylogeny, Escherichia coli Infections microbiology, Escherichia coli Proteins genetics, Escherichia coli Proteins metabolism, Meningitis
Abstract

Bacteria adapt to selective pressure in their immediate environment in multiple ways. One mechanism involves the acquisition of independent mutations that disable or modify a key pathway, providing a signature of adaptation via convergent evolution. Extra-intestinal pathogenic Escherichia coli (ExPEC) belonging to sequence type 95 (ST95) represent a global clone frequently associated with severe human infections including acute pyelonephritis, sepsis, and neonatal meningitis. Here, we analysed a publicly available dataset of 613 ST95 genomes and identified a series of loss-of-function mutations that disrupt cellulose production or its modification in 55.3% of strains. We show the inability to produce cellulose significantly enhances ST95 invasive infection in a rat model of neonatal meningitis, leading to the disruption of intestinal barrier integrity in newborn pups and enhanced dissemination to the liver, spleen and brain. Consistent with these observations, disruption of cellulose production in ST95 augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of urinary tract infection. Mutations that disrupt cellulose production were also identified in other virulent ExPEC STs, Shigella and Salmonella, suggesting a correlative association with many Enterobacteriaceae that cause severe human infection. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones., (© 2024. The Author(s).)

Published
2024
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2. Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria.

Author

Mu A, Klare WP, Baines SL, Ignatius Pang CN, Guérillot R, Harbison-Price N, Keller N, Wilksch J, Nhu NTK, Phan MD, Keller B, Nijagal B, Tull D, Dayalan S, Chua HHC, Skoneczny D, Koval J, Hachani A, Shah AD, Neha N, Jadhav S, Partridge SR, Cork AJ, Peters K, Bertolla O, Brouwer S, Hancock SJ, Álvarez-Fraga L, De Oliveira DMP, Forde B, Dale A, Mujchariyakul W, Walsh CJ, Monk I, Fitzgerald A, Lum M, Correa-Ospina C, Roy Chowdhury P, Parton RG, De Voss J, Beckett J, Monty F, McKinnon J, Song X, Stephen JR, Everest M, Bellgard MI, Tinning M, Leeming M, Hocking D, Jebeli L, Wang N, Ben Zakour N, Yasar SA, Vecchiarelli S, Russell T, Zaw T, Chen T, Teng D, Kassir Z, Lithgow T, Jenney A, Cole JN, Nizet V, Sorrell TC, Peleg AY, Paterson DL, Beatson SA, Wu J, Molloy MP, Syme AE, Goode RJA, Hunter AA, Bowland G, West NP, Wilkins MR, Djordjevic SP, Davies MR, Seemann T, Howden BP, Pascovici D, Tyagi S, Schittenhelm RB, De Souza DP, McConville MJ, Iredell JR, Cordwell SJ, Strugnell RA, Stinear TP, Schembri MA, and Walker MJ

Subjects
Humans, Anti-Bacterial Agents therapeutic use, Proteomics, Bacteria, Escherichia coli, Klebsiella, Microbial Sensitivity Tests, Sepsis microbiology, Staphylococcal Infections
Abstract

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research., (© 2023. The Author(s).)

Published
2023
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3. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Author

Pattaro C, Teumer A, Gorski M, Chu AY, Li M, Mijatovic V, Garnaas M, Tin A, Sorice R, Li Y, Taliun D, Olden M, Foster M, Yang Q, Chen MH, Pers TH, Johnson AD, Ko YA, Fuchsberger C, Tayo B, Nalls M, Feitosa MF, Isaacs A, Dehghan A, d'Adamo P, Adeyemo A, Dieffenbach AK, Zonderman AB, Nolte IM, van der Most PJ, Wright AF, Shuldiner AR, Morrison AC, Hofman A, Smith AV, Dreisbach AW, Franke A, Uitterlinden AG, Metspalu A, Tonjes A, Lupo A, Robino A, Johansson Å, Demirkan A, Kollerits B, Freedman BI, Ponte B, Oostra BA, Paulweber B, Krämer BK, Mitchell BD, Buckley BM, Peralta CA, Hayward C, Helmer C, Rotimi CN, Shaffer CM, Müller C, Sala C, van Duijn CM, Saint-Pierre A, Ackermann D, Shriner D, Ruggiero D, Toniolo D, Lu Y, Cusi D, Czamara D, Ellinghaus D, Siscovick DS, Ruderfer D, Gieger C, Grallert H, Rochtchina E, Atkinson EJ, Holliday EG, Boerwinkle E, Salvi E, Bottinger EP, Murgia F, Rivadeneira F, Ernst F, Kronenberg F, Hu FB, Navis GJ, Curhan GC, Ehret GB, Homuth G, Coassin S, Thun GA, Pistis G, Gambaro G, Malerba G, Montgomery GW, Eiriksdottir G, Jacobs G, Li G, Wichmann HE, Campbell H, Schmidt H, Wallaschofski H, Völzke H, Brenner H, Kroemer HK, Kramer H, Lin H, Leach IM, Ford I, Guessous I, Rudan I, Prokopenko I, Borecki I, Heid IM, Kolcic I, Persico I, Jukema JW, Wilson JF, Felix JF, Divers J, Lambert JC, Stafford JM, Gaspoz JM, Smith JA, Faul JD, Wang JJ, Ding J, Hirschhorn JN, Attia J, Whitfield JB, Chalmers J, Viikari J, Coresh J, Denny JC, Karjalainen J, Fernandes JK, Endlich K, Butterbach K, Keene KL, Lohman K, Portas L, Launer LJ, Lyytikäinen LP, Yengo L, Franke L, Ferrucci L, Rose LM, Kedenko L, Rao M, Struchalin M, Kleber ME, Cavalieri M, Haun M, Cornelis MC, Ciullo M, Pirastu M, de Andrade M, McEvoy MA, Woodward M, Adam M, Cocca M, Nauck M, Imboden M, Waldenberger M, Pruijm M, Metzger M, Stumvoll M, Evans MK, Sale MM, Kähönen M, Boban M, Bochud M, Rheinberger M, Verweij N, Bouatia-Naji N, Martin NG, Hastie N, Probst-Hensch N, Soranzo N, Devuyst O, Raitakari O, Gottesman O, Franco OH, Polasek O, Gasparini P, Munroe PB, Ridker PM, Mitchell P, Muntner P, Meisinger C, Smit JH, Kovacs P, Wild PS, Froguel P, Rettig R, Mägi R, Biffar R, Schmidt R, Middelberg RP, Carroll RJ, Penninx BW, Scott RJ, Katz R, Sedaghat S, Wild SH, Kardia SL, Ulivi S, Hwang SJ, Enroth S, Kloiber S, Trompet S, Stengel B, Hancock SJ, Turner ST, Rosas SE, Stracke S, Harris TB, Zeller T, Zemunik T, Lehtimäki T, Illig T, Aspelund T, Nikopensius T, Esko T, Tanaka T, Gyllensten U, Völker U, Emilsson V, Vitart V, Aalto V, Gudnason V, Chouraki V, Chen WM, Igl W, März W, Koenig W, Lieb W, Loos RJ, Liu Y, Snieder H, Pramstaller PP, Parsa A, O'Connell JR, Susztak K, Hamet P, Tremblay J, de Boer IH, Böger CA, Goessling W, Chasman DI, Köttgen A, Kao WH, and Fox CS

Subjects
Gene Expression Regulation, Genome-Wide Association Study, Genotype, Humans, Genetic Predisposition to Disease, Renal Insufficiency, Chronic genetics
Abstract

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Published
2016
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