Bacterial Pathogenesis and Immunity

The Kadioglu research group visit to the Peak District

Recent Publications

Dairy heifers naturally exposed to Fasciola hepatica develop a type-2 immune response and concomitant suppression of leukocyte proliferation. Graham-Brown, J., Hartley, C., Clough, H., Kadioglu, A., Baylis, M. and Williams, D. Infection and Immunity Oct 2017. doi: 10.1128/IAI.00607-17.

Comparative Genomic Analysis and In Vivo Modeling of Streptococcus pneumoniae ST3081 and ST618 Isolates Reveal Key Genetic and Phenotypic Differences Contributing to Clonal Replacement of Serotype 1 in The Gambia. Bricio-Moreno, L., Ebruke, C., Chaguza, C., Cornick, J., Kwambana-Adams, B., Yang, M., Mackenzie, G., Wren, B., Everett, D., Antonio, M. and Kadioglu, A. The Journal of Infectious Diseases Sept 2017. doi: 10.1093/infdis/jix472

The accessory Sec system (SecY2A2) in Streptococcus pneumoniae is involved in export of pneumolysin  toxin, adhesion and biofilm formation. Bandara M, Skehel JM, Kadioglu A, Collinson I, Nobbs AH, BlockerAJ, Jenkinson HF. Microbes Infect. 2017 Jul - Aug;19(7-8):402-412

Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi.Chaguza C, Cornick JE, Andam CP, Gladstone RA, Alaerts M, Musicha P, Peno C, Bar-Zeev N, Kamng'ona AW, Kiran AM, Msefula CL, McGee L, Breiman RF, Kadioglu A, French N, Heyderman RS, Hanage WP, Bentley SD, Everett DB.Vaccine. 2017 Jul 12. pii: S0264-410X(17)30905-2

Phage therapy is highly effective against chronic lung infections with Pseudomonas aeruginosa. Waters EM, Neill DR, Kaman B, Sahota JS, Clokie MR, Winstanley C, Kadioglu A. Thorax. 2017 Mar 6. pii: thoraxjnl-2016-209265. doi:10.1136/thoraxjnl-2016-209265.

The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1.Cornick JE, Tastan Bishop Ö, Yalcin F, Kiran AM, Kumwenda B, Chaguza C, Govindpershad S, Ousmane S, Senghore M, du Plessis M, Pluschke G, Ebruke C, McGee L, Sigaùque B, Collard JM, Bentley
SD, Kadioglu A, Antonio M, von Gottberg A, French N, Klugman KP, Heyderman RS, Alderson M, Everett DB; PAGe consortium. Vaccine. 2017 Feb 7;35(6):972-980. doi: 10.1016/j.vaccine.2016.12.037

Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections. Waters E, Rudkin JK, Coughlan S, Clair GC, Adkins JN, Gore S, Xia G, Black NS, Downing T, O'Neill E, Kadioglu A, O'Gara JP.J Infect Dis. 2017 Jan 1;215(1):80-87. doi: 10.1093/infdis/jiw461.

Understanding pneumococcal serotype 1 biology through population genomic analysis. Chaguza C, Cornick JE, Harris SR, Andam CP, Bricio-Moreno L, Yang M, Yalcin F, Ousmane S, Govindpersad S, Senghore M, Ebruke C, Du Plessis M, Kiran AM, Pluschke G, Sigauque B, McGee L, Klugman KP, Turner P, Corander J, Parkhill J, Collard JM, Antonio M, von Gottberg A, Heyderman RS, French N, Kadioglu A, Hanage WP, Everett DB, Bentley SD; PAGe Consortium. BMC Infect Dis. 2016 Nov 8;16(1):649.

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule.
Chaguza C, Andam CP, Harris SR, Cornick JE, Yang M, Bricio-Moreno L, Kamng'ona AW, Parkhill J, French N, Heyderman RS, Kadioglu A, Everett DB, Bentley SD, Hanage WP.MBio. 2016 Sep 27;7(5). pii: e01053-16. doi: 10.1128/mBio.01053-16.

Understanding pneumococcal serotype 1 biology through population genomic analysis.
Chaguza C, Cornick JE, Harris SR, Andam CP, Bricio-Moreno L, Yang M, Yalcin F, Ousmane S, Govindpersad S, Senghore M, Ebruke C, Du Plessis M, Kiran AM, Pluschke G, Sigauque B, McGee L, Klugman KP, Turner P, Corander J, Parkhill J, Collard JM, Antonio M, von Gottberg A, Heyderman RS, French N, Kadioglu A, Hanage WP, Everett DB, Bentley SD; PAGe Consortium..BMC Infect Dis. 2016 Nov 8;16(1):649.

Airborne dust and high temperatures are risk factors for invasive bacterial disease.
Jusot JF, Neill DR, Waters EM, Bangert M, Collins M, Bricio Moreno L, Lawan KG, Moussa MM, Dearing E, Everett DB, Collard JM, Kadioglu A.J Allergy Clin Immunol. 2016 Jul 14. pii: S0091-6749(16)30616-9. doi: 10.1016/j.jaci.2016.04.062

Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in Severe Sepsis.
Morton B, Mitsi E, Pennington SH, Reiné J, Wright AD, Parker R, Welters ID, Blakey JD, Rajam G, Ades EW, Ferreira DM, Wang D, Kadioglu A, Gordon SB.Shock. 2016 Dec;46(6):635-641.

Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection.
Alhamdi Y, Neill DR, Abrams ST, Malak HA, Yahya R, Barrett-Jolley R, Wang G, Kadioglu A, Toh CH.PLoS Pathog. 2015 May 14;11(5):e1004836. doi: 10.1371/journal.ppat.1004836.

Bacteriophage Delivery by Nebulization and Efficacy Against Phenotypically Diverse Pseudomonas aeruginosa from Cystic Fibrosis Patients.
Sahota JS, Smith CM, Radhakrishnan P, Winstanley C, Goderdzishvili M, Chanishvili N, Kadioglu A, O'Callaghan C, Clokie MR.J Aerosol Med Pulm Drug Deliv. 2015 Oct;28(5):353-60. doi: 10.1089/jamp.2014.1172.

Neutrophil IL-1β processing induced by pneumolysin is mediated by the NLRP3/ASC inflammasome and caspase-1 activation and is dependent on K+ efflux.
Karmakar M, Katsnelson M, Malak HA, Greene NG, Howell SJ, Hise AG, Camilli A, Kadioglu A, Dubyak GR, Pearlman E.J Immunol. 2015 Feb 15;194(4):1763-75. doi: 10.4049/jimmunol.1401624.

Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice.
Henry BD, Neill DR, Becker KA, Gore S, Bricio-Moreno L, Ziobro R, Edwards MJ, Mühlemann K, Steinmann J, Kleuser B, Japtok L, Luginbühl M, Wolfmeier H, Scherag A, Gulbins E, Kadioglu A, Draeger A, Babiychuk EB.Nat Biotechnol. 2015 Jan;33(1):81-8. doi: 10.1038/nbt.3037.

Ca²⁺-dependent repair of pneumolysin pores: A new paradigm for host cellular defense against bacterial pore-forming toxins.
Wolfmeier H, Schoenauer R, Atanassoff AP, Neill DR, Kadioglu A, Draeger A, Babiychuk EB.Biochim Biophys Acta. 2015 Sep;1853(9):2045-54. doi: 10.1016/j.bbamcr.2014.09.005.

Pseudomonas aeruginosa adaptation in the nasopharyngeal reservoir leads to migration and persistence in the lungs.
Fothergill JL, Neill DR, Loman N, Winstanley C, Kadioglu A.Nat Commun. 2014 Sep 2;5:4780. doi: 10.1038/ncomms5780.

Density and duration of experimental human pneumococcal carriage.
Gritzfeld JF, Cremers AJ, Ferwerda G, Ferreira DM, Kadioglu A, Hermans PW, Gordon SB.Clin Microbiol Infect. 2014 Dec;20(12):O1145-51. doi: 10.1111/1469-0691.12752.

A new protective role for S100A9 in regulation of neutrophil recruitment during invasive pneumococcal pneumonia.
De Filippo K, Neill DR, Mathies M, Bangert M, McNeill E, Kadioglu A, Hogg N. FASEB J. 2014 Aug;28(8):3600-8. doi: 10.1096/fj.13-247460. Epub 2014 Apr 28.

Density and duration of pnuemococcal carriage is maintained by transforming growth factor beta 1 and T regulatory cells
Neill DR, Coward WR, Gritzfeld JF, Richards L, Garcia-Garcia FJ, Dotor J, Gordon SB, Kadioglu A. Am J Respir Crit Care Med. 2014 May 15;189(10):1250-9. doi: 10.1164/rccm.201401-0128OC.

Septicaemia models using Streptococcus pneumoniae and Listeria monocytogenes: understanding the role of complement properdin.
Dupont A, Mohamed F, Salehen N, Glenn S, Francescut L, Adib R, Byrne S, Brewin H, Elliott I, Richards L, Dimitrova P, Schwaeble W, Ivanovska N, Kadioglu A, Machado LR, Andrew PW, Stover C.Med Microbiol Immunol. 2014 Aug;203(4):257-71. doi: 10.1007/s00430-013-0324-z.

Streptococcus pneumoniae detects and responds to foreign bacterial peptide fragments in its environment.
Hathaway LJ, Bättig P, Reber S, Rotzetter JU, Aebi S, Hauser C, Heller M, Kadioglu A, Mühlemann K
Open Biol. 2014 Apr 9;4:130224. doi: 10.1098/rsob.130224.

The pneumococcal polysaccharide capsule and pneumolysin differentially affect CXCL8 and IL-6 release from cells of the upper and lower respiratory tract.
Küng E, Coward WR, Neill DR, Malak HA, Mühlemann K, Kadioglu A, Hilty M, Hathaway LJ. PLoS One. 2014 Mar 24;9(3):e92355. doi: 10.1371/journal.pone.0092355.

Spir2; a novel QTL on chromosome 4 contributes to susceptibility to pneumococcal infection in mice.
Wisby L, Fernandes VE, Neill DR, Kadioglu A, Andrew PW, Denny P. BMC Genomics. 2013 April 11; 14:242. doi:10.1186/1471-2164-14-242.

Immunoactivating peptide P4 augments alveolar macrophage phagocytosis in two diverse human population
Bangert M, Wright AK, Rylance J, Kelly M, Wright A, Carlone GM, Sampson JS, Rajam G, Ades EW, Kadioglu A, Gordon SB. Antimicrobial Agents and Chemotherapy. 2013 Sep; 57(9):4566-9. doi: 10.1128/AAC.00742-13.

The AgI/II family adhesion AspA is required for respiratory infection by Streptococcus pyogenes.
Franklin L, Nobbs A.H., Bricio-Moreno L, Wright C.J., Maddocks S.E., Singh-Sahota J, Ralph J, O’Connor M, Jenkinson H.F., and Kadioglu A.PlosOne. 2013 Apr 30;8(4):e62433. doi: 10.1371/journal.pone.0062433.

Experimental Human Carriage.
Gritzfeld JF, Wright AD, Collins AM, Pennington SH, Wright AK, Kadioglu A, Ferreira DM, Gordon SB. J Vis Exp. 2013 Feb 15;(72). pii: 50115. doi: 10.3791/50115.

Controlled Human Infection and Re-Challenge with Streptococcus Pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults.
Ferreira DM, Neill DR, Bangert M, Gritzfeld JF, Green N, Wright AK, Pennington SH, Moreno LB, Moreno AT, Miyaji EN, Wright AD, Collins AM, Goldblatt D, Kadioglu A, Gordon SB. Am J Respir Crit Care Med. 2013 Jan 31.

Nasopharyngeal carriage with Streptococcus pneumoniae augments the immunizingeffect of pneumolysin toxoid B.
Neill DR, Smeaton S, Bangert M, Kadioglu AJ Allergy Clin Immunol.  2012 Dec 18. doi:pii: S0091-6749(12)01779-4.

The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection.
Ali YM, Lynch NJ, Haleem KS, Fujita T, Endo Y, Hansen S, Holmskov U, Takahashi K, Stahl GL, Dudler T, Girija UV, Wallis R, Kadioglu A, Stover CM, Andrew PW, Schwaeble WJ. PLoS Pathog. 2012;8(7):e1002793. doi: 10.1371/journal.ppat.1002793. Epub 2012 Jul 5.

T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.
Neill DR, Fernandes VE, Wisby L, Haynes AR< Ferreira DM, Laher A, Strickland N, Gordon SB, Denny P, Kadioglu A, Andrew PW.  PloS Pathog. 2012 Apr:8(4):e1002660. Epub 2012 Apr 19.

Nicotinamide nucleotide transhydrogenase (NNT) acts as a novel modulator of macrophage inflammatory responses.
Ripoll VM, Meadows NA, Bangert M, Lee AW, Kadioglu, Cox RD. The FASEB Journal 2012, doi:10.1097/fj.11-199935

P4 Mediated antibody therapy in an acute model of invasive pneumococcal disease.
Bangert M, Bricio-Moreno L, Gore S, Rajam G, Ades EW, Gordon SB, Kadioglu A.J Infect Dis. 2012 March 29.

T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.
Neill DR, Fernandes VE, Wisby L, Jaynes A, Ferreira D, Laher A, Strickland N, Gordon SB, Denny P, Kadioglu A, Andrew PW.PLoS Pathog. 2012, 2012;8(4):e1002660.

Death is associated with complement c3 depletion in cerebrospinal fluid of patients with pneumococcal meningitis.
Goonetilleke UR, Scarborough M, Ward SA, Hussain S, Kadioglu A, Gordon SB. MBio. 2012 March 13;3(2). pii: e00272-11. doi: 10.1128/mBio.00272-11.

Capsule type of streptococcus pneumoniae determines growth phenotype.
Hathaway LJ, Brugger SD, Morand B, Bangert M, Rotzetter JU, Hauser C, Graber WA, Gore S, Kadioglu A, Mühlemann K.
PLoS Pathog. 2012 Mar; 8(3): e1002574. Epub 2012 Mar.8

Novel applications of P4 mediated antibody therapy in an acute setting of invasive pneumococcal disease.
Bangert M, Bricio-Moreno L, Gore S, Rajam G, Ades EW, Gordon SB, Kadioglu A
J Infect Dis. 2012 In Press

Persistence of Pneumolysin in the Cerebrospinal Fluid of Patients With Pneumococcal Meningitis Is Associated With Mortality.
Wall EC, Gordon SB, Hussain S, Goonetilleke UR, Grizfield J, Scarborough M, Kadioglu A.
Clin Infect Dis. 2012 Jan 11

Absence of the lectin activation pathway of complement does not increase susceptibility to Pseudomonas aeruginosa infections.
Kenawy HI, Ali YM, Rajakumar K, Lynch NJ, Kadioglu A, Stover CM, Schwaeble WJ.
Immunobiology. 2012 Feb;217(2):272-80.


Selected Previous Publications

Sex-based differences in susceptibility to respiratory and systemic pneumococcal disease in mice.
Kadioglu A, Cuppone AM, Trappetti C, List T, Spreafico A, Pozzi G, Andrew PW, Oggioni MR.
J Infect Dis. 2011 Dec 15;204(12):1971-9.

Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4.
McNeela EA, Burke A, Neill DR, Baxter C, Fernandes VE, Ferreira D, Smeaton S, El-Rachkidy R, McLoughlin RM, Mori A, Moran B, Fitzgerald KA, Tschopp J, Pétrilli V, Andrew PW, Kadioglu A, Lavelle EC.
PLoS Pathog. 2010 Nov 11;6(11):e1001191

The immunising effect of pneumococcal nasopharyngeal colonisation; protection against future colonisation and fatal invasive disease.
Richards L, Ferreira DM, Miyaji EN, Andrew PW, Kadioglu A.
Immunobiology. 2010 Apr;215(4):251-63

The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease.
Kadioglu A, Weiser JN, Paton JC, Andrew PW.
Nat Rev Microbiol. 2008 Apr;6(4):288-301. Review.

Pneumococcal neuraminidases A and B both have essential roles during infection of the respiratory tract and sepsis.
Manco S, Hernon F, Yesilkaya H, Paton JC, Andrew PW, Kadioglu A.
Infect Immun. 2006 Jul;74(7):4014-20

CD4-T-lymphocyte interactions with pneumolysin and pneumococci suggest a crucial protective role in the host response to pneumococcal infection.
Kadioglu A, Coward W, Colston MJ, Hewitt CR, Andrew PW.
Infect Immun. 2004 May;72(5):2689-97

The innate immune response to pneumococcal lung infection: the untold story.
Kadioglu A, Andrew PW.
Trends Immunol. 2004 Mar;25(3):143-9.

Upper and lower respiratory tract infection by Streptococcus pneumoniae is affected by pneumolysin deficiency and differences in capsule type.
Kadioglu A, Taylor S, Iannelli F, Pozzi G, Mitchell T, Andrew PW
Infect Immun. 2002 70:2886-90

Role of genetic resistance in invasive pneumococcal infection: identification and study of susceptibility and resistance in inbred mouse strains.
Gingles NA, Alexander JE, Kadioglu A, Andrew PW, Kerr A, Mitchell TJ, Hopes E, Denny P, Brown S, Jones HB, Little S, Booth GC, McPheat WL.
Infect Immun. 2001 Jan;69(1):426-34.

Host cellular immune response to pneumococcal lung infection in mice.
Kadioglu A, Gingles NA, Grattan K, Kerr A, Mitchell TJ, Andrew PW.
Infect Immun. 2000 Feb;68(2):492-501