Staff Profile
Dr Phillip Aldridge
Senior Lecturer
- Email: [email protected]
- Telephone: +44 (0) 191 208 3218
- Address: Biosciences Institute
Faculty of Medical Sciences
Newcastle University
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom
Qualifications
BSc. - Leicester 1993
PhD. - Leicester and Heidelberg (Germany) 1998
Previous Positions
1996 to 2000 Division of Mol. Microbiology, Biozentrum, University of Basel, Basel, Switerland
2000 to 2003 Dept. of Microbiology, University of Washington, Seattle, WA, USA
Memberships
Society for General Microbiology
Society for Applied Microbiology
1) Urinary Tract Infections
Urinary tract infections (UTIs) are a common bacterial infection with symptoms that include urinary frequency, urgency to void, dysuria and abdominal pain. At present it is assumed that the relationship between an individual’s susceptibility and bacterial virulence determines the balance between tolerance of invading pathogens and the mounting of an immune response, which in turn dictates the course of infection and subsequent recurrence. The lack of specific genomic and phenotypic information makes it challenging to differentiate between uropathogenic E. coli (UPEC) and asymptomatic bacteriuria (ABU) E. coli strains. One outcome is that ABU patients, particularly the elderly, are often given antibiotics without justification due to clinical uncertainty.
This work on UTIs is a collaborative project between myself, a further university-based academic, a urological consultant surgeon and a uro-gynaecological consultant. Our partnership objectives focus on an unmet need to generate robust data on the clinical efficacy and underlying scientific mechanisms of antibiotic and non-antibiotic preventive interventions for UTIs directly in line with global antibiotic stewardship initiatives. We have developed a robust research framework integrating basic scientific research into clinical studies and trials to inform clinical decisions, impact antibiotic stewardship and importantly, improve patient well-being.
The team’s research strategy aims to:
- Utilise clinical studies and patient material to interrogate and understand recurrent UTI;
- Combine basic and clinical approaches for the benefit of patients suffering recurrent UTI;
- Educate and attract young scientists and clinicians to the study of urology and UTI.
2) The bacterial flagellum
The flagellum is a unique molecular machine driving bacterial movement through liquid environments. Bacteria are propelled forward by rotation of an external long whip-like flagellar filament. Rotation of the filament is achieved via the action of a universal joint known as the hook and a basal motor anchored into the bacterial cell envelope. The flagellar filament is a major antigen recognized by hosts during bacterial infections. A significant number of bacterial species encode multiple copies of the filament building block - flagellin. A complex regulatory network controls the assembly of the flagellum and the number per cell, which varies between different species.
Our research focuses on the fundamental understanding of how bacteria regulate flagellar assembly, how a cell coordinates the assembly of unrelated molecular machines and how hosts recognise this important antigen. We have studied how bacterial species such as the pathogen Salmonella enterica maintain a discrete number of flagellar per cell during cell growth and division. We complement our study on flagellar abundance with research to understanding how a filament is assembled from multiple flagellins, a trait maintained by many bacterial species. Our in-depth knowledge of flagellar assembly and its regulation allow us to investigate the interaction of the host innate immune system during UTIs.
Expertise
My expertise utilise bacterial genetics to study fundamental aspects of the bacterial life cycle and host-microbe interactions. My laboratory uses, bacterial genetics, protein biochemistry, structural biology, bioinformatics and microscopic techniques to validate our genetic findings.
I also have a strong background in bacterial pathogenesis of both Animal and Plant Hosts. During my career I have gained valuable experience working with a range of bacterial pathogens.
Postgraduate Supervision
A wide range of projects are available.
Undergraduate Teaching
BMS3025 - Module Leader
CMB3000 - Project Supervisor
Postgraduate Teaching
MMB8048 - Module Leader
MMB8098 - Deputy Module Leader
PhD. Supervisor for 1 student
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Articles
- Mowbray C, Tan A, Vallee M, Fisher H, Chadwick T, Brennand C, Walton KE, Pickard RS, Harding C, Aldridge PA, Hall J. Multidrug-resistant Uro-associated Escherichia coli Populations and Recurrent Urinary Tract Infections in Patients Performing Clean Intermittent Self-catheterisation. European Urology Open Science 2022, 37, 90-98.
- Vallee M, Harding C, Hall J, Aldridge P, Tan A. Exploring the in situ evolution of nitrofurantoin resistance in clinically derived uropathogenic Escherichia coli isolates. Journal of Antimicrobial Chemotherapy 2023, 78(2), 373-379.
- Wang X, Koirala S, Aldridge PD, Rao CV. Two Tandem Mechanisms Control Bimodal Expression of the Flagellar Genes in Salmonella enterica. Journal of Bacteriology 2020, 202(13), e00787-19.
- Hamed S, Wang X, Shawky RM, Emara M, Aldridge PD, Rao CV. Synergistic action of SPI-1 gene expression in Salmonella enterica serovar typhimurium through transcriptional crosstalk with the flagellar system. BMC Microbiology 2019, 19(1), 211.
- Mickiewicz KM, Kawai Y, Drage L, Gomes MC, Davison F, Pickard R, Hall J, Mostowy S, Aldridge PD, Errington J. Possible role of L-form switching in recurrent urinary tract infection. Nature Communications 2019, 10(1), 4379.
- Drage LKL, Robson W, Mowbray C, Ali A, Perry JD, Walton KE, Harding C, Pickard R, Hall J, Aldridge PD. Elevated urine IL-10 concentrations associate with Escherichia coli persistence in older patients susceptible to recurrent urinary tract infections. Immunity and Ageing 2019, 16(1).
- Byrne M, Singh A, Mowbray CA, Aldridge PD, Drage LKL, Ali ASM, Bates L, Hall J, Wilson C. Bladder-Drained Pancreas Transplantation: Urothelial Innate Defenses and UTI Susceptibility. Journal of Surgical Research 2019, 235, 288-297.
- Mowbray CA, Shams S, Chung G, Stanton A, Aldridge P, Suchenko A, Pickard RS, Ali ASM, Hall J. High molecular weight hyaluronic acid: a two-pronged protectant against infection of the urogenital tract?. Clinical & Translational Immunology 2018, 7(6), e1021.
- Albanna A, Sim M, Hoskisson PA, Gillespie C, Rao CV, Aldridge PD. Driving the expression of the Salmonella enterica sv Typhimurium flagellum using flhDC from Escherichia coli results in key regulatory and cellular differences. Scientific Reports 2018, 8(1), 16705.
- Ali ASM, Mowbray C, Lanz M, Stanton A, Bowen S, Varley CL, Hilton P, Brown K, Robson W, Southgate J, Aldridge P, Tyson-Capper A, Abraham S, Pickard RS, Hall J. Targeting Deficiencies in the TLR5 Mediated Vaginal Response to Treat Female Recurrent Urinary Tract Infection. Scientific Reports 2017, 7, 11039.
- Sim M, Koirala S, Picton D, Strahl H, Hoskissin PA, Rao CV, Gillespie CS, Aldridge PD. Growth rate control of flagellar assembly in Escherichai coli strain RP437. Scientific Reports 2017, 7, 41189.
- Minamino T, Morimoto YV, Hara N, Aldridge PD, Namba K. The Bacterial Flagellar Type III Export Gate Complex Is a Dual Fuel Engine That Can Use Both H+ and Na+ for Flagellar Protein Export. PLoS Pathogens 2016, 12(3), e1005495.
- Minamino T, Morimoto YV, Kinoshita M, Aldridge PD, Namba K. The bacterial flagellar protein export apparatus processively transports flagellar proteins even with extremely infrequent ATP hydrolysis. Scientific Reports 2014, 4, 7579.
- Cairns LS, Marlow VL, Kiley TB, Birchall C, Ostrowski A, Aldridge PD, Stanley-Wall NR. FlgN Is Required for Flagellum-Based Motility by Bacillus subtilis. Journal of Bacteriology 2014, 196(12), 2216-2226.
- Koirala A, Mears P, Sim M, Golding I, Chemla YR, Aldridge PD, Rao CV. A Nutrient-Tunable Bistable Switch Controls Motility in Salmonella enterica Serovar Typhimurium. mBio 2014, 5(5), e01611-14.
- Minamino T, Kinoshita M, Hara N, Takeuchi S, Hida A, Koya S, Glenwright H, Imada K, Aldridge PD, Namba K. Interaction of a bacterial flagellar chaperone FlgN with FlhA is required for efficient export of its cognate substrates. Molecular Microbiology 2012, 83(4), 775-788.
- Faulds-Pain A, Birchall C, Aldridge C, Smith WD, Grimaldi G, Nakamura S, Miyata T, Gray J, Li GL, Tang JX, Namba K, Minamino T, Aldridge PD. Flagellin Redundancy in Caulobacter crescentus and Its Implications for Flagellar Filament Assembly. Journal of Bacteriology 2011, 193(11), 2695-2707.
- Saini S, Floess E, Aldridge C, Brown J, Aldridge PD, Rao CV. Continuous control of flagellar gene expression by the σ28–FlgM regulatory circuit in Salmonella enterica. Molecular Microbiology 2011, 79(1), 264-278.
- Pohl S, Tu WY, Aldridge PD, Gillespie C, Hahne H, Mäder U, Read TD, Harwood CR. Combined proteomic and transcriptomic analysis of the response of Bacillus anthracis to oxidative stress. Proteomics 2011, 11(15), 3036-3055.
- Aldridge C, Poonchareon K, Saini S, Ewen T, Soloyva A, Rao CV, Imada K, Minamino T, Aldridge PD. The interaction dynamics of a negative feedback loop regulates flagellar number in Salmonella enterica serovar Typhimurium. Molecular Microbiology 2010, 78(6), 1416-1430.
- Saini S, Koirala S, Floess E, Mears PJ, Chemla TR, Golding I, Aldridge C, Aldridge PD, Rao CV. FliZ induces a kinetic switch in flagellar gene expression. Journal of Bacteriology 2010, 192(24), 6477-6481.
- Scharf BE, Aldridge PD, Kirby JR, Crane BR. Upward mobility and alternative lifestyles: a report from the 10th biennial meeting on Bacterial Locomotion and Signal Transduction. Molecular Microbiology 2009, 73(1), 5-19.
- Brown JD, Saini S, Aldridge C, Herbert J, Rao CV, Aldridge PD. The rate of protein secretion dictates the temporal dynamics of flagellar gene expression. Molecular Microbiology 2008, 70(4), 924-937.
- Saini S, Brown JD, Aldridge PD, Rao CV. FliZ is a posttranslational activator of FlhD4C 2-dependent flagellar gene expression. Journal of Bacteriology 2008, 190(14), 4979-4988.
- Aldridge P, Gnerer J, Karlinsey JE, Hughes KT. Transcriptional and translational control of the Salmonella fliC gene. Journal of Bacteriology 2006, 188(12), 4487-4496.
- Aldridge PD, Karlinsey JE, Aldridge C, Birchall C, Thompson D, Yagasaki J, Hughes KT. The flagellar-specific transcription factor, σ28, is the Type III secretion chaperone for the flagellar-specific anti- σ28 factor FlgM. Genes & Development 2006, 20(16), 2315-2326.
- Aldridge PD, Wu C, Gnerer J, Karlinsey JE, Hughes KT, Sachs MS. Regulatory protein that inhibits both synthesis and use of the target protein controls flagellar phase variation in Salmonella enterica. Proceedings of the National Academy of Sciences of the United States of America 2006, 103(30), 11340-11345.
- Aldridge P, Karlinsey JE, Becker E, Chevance FFV, Hughes KT. Flk prevents premature secretion of the anti-σ factor FlgM into the periplasm. Molecular Microbiology 2006, 60(3), 630-642.
- Aldridge P, Karlinsey J, Hughes KT. The type III secretion chaperone FlgN regulates flagellar assembly via a negative feedback loop containing its chaperone substrates FlgK and FlgL. Molecular Microbiology 2003, 49(5), 1333-1345.
- Aldridge P, Paul R, Goymer P, Rainey P, Jenal U. Role of the GGDEF regulator PleD in polar development of Caulobacter crescentus. Molecular Microbiology 2003, 47(6), 1695-1708.
- Fischer B, Rummel G, Aldridge P, Jenal U. The FtsH protease is involved in development, stress response and heat shock control in Caulobacter crescentus. Molecular Microbiology 2002, 44(2), 461-478.
- Aldridge P, Hughes KT. Regulation of flagellar assembly. Current Opinion in Microbiology 2002, 5(2), 160-165.
- Hughes KT, Aldridge PD. Putting a lid on it. Nature Structural and Molecular Biology 2001, 8(2), 96-97.
- Aldridge P, Hughes KT. How and when are substrates selected for type III secretion?. Trends in Microbiology 2001, 9(5), 209-214.
- Aldridge P, Jenal U. Cell cycle-dependent degradation of a flagellar motor component requires a novel-type response regulator. Molecular Microbiology 1999, 32(2), 379-391.
- P. Aldridge,F. Bernhard,P. Bugert,D. L. Coplin,K. Geider. Characterization of a gene locus from Erwinia amylovora with regulatory functions in exopolysaccharide synthesis of Erwinia spp. Can J Microbiol 1998, 44(7), 657-66.
- S. Bereswill,P. Aldridge,J.G. Janse,K. Geider. Partial characterization of natural levan deficient Erwinia amylovora strains. 51: 215-225. Physiological and Molecular Plant Pathology 1997, 51, 215-225.
- P. Aldridge,M. Metzger,K. Geider. Genetics of sorbitol metabolism in Erwinia amylovora and its influence on bacterial virulence. Mol Gen Genet 1997, 256(6), 611-9.
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Book Chapter
- Brown J, Faulds-Pain A, Aldridge P. The Coordination of Flagellar Gene Expression and the Flagellar Assembly Pathway. In: Jarrell KF, ed. Pili and Flagellar: Current Research and Future Trends. Norwich: Caister Academic Press, 2009, pp.99-120.
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Conference Proceedings (inc. Abstracts)
- Drage L, Lanz M, Ali A, Birchall C, Hall J, Pickard R, Aldridge P. Uropathogenic Escherichia coli behaviour in different growth mediums and avoidance of the innate immune response. In: Annual Meeting of the Society-of-Academic-and-Research-Surgery. 2014, Univ Cambridge, Robinson Coll, Cambridge, ENGLAND: John Wiley & Sons Ltd.
- Lanz ML, Aldridge P, Birchall C, Ali A, Townes C, Walton K, Lim LY, Pickard RS, Hall J. Comparison of the motility and NF-Kappab activating properties of clinical isolates associated with urinary tract infections. In: Annual Meeting of the Society of Academic and Research Surgery. 2013, Royal Soc Med (RSM), London, ENGLAND: John Wiley & Sons Ltd.
- Aldridge PD, Gray MA, Hirst BH, Khan CMA. Who's talking to whom? Epithelial-bacterial pathogen interactions. In: International Symposium on Epithelial-Bacterial Pathogen Interactions. 2004, Newcastle upon Tyne, UK: Molecular Microbiology: Wiley-Blackwell.
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Note
- Mickiewicz KM, Kawai Y, Drage L, Gomes MC, Davison F, Pickard R, Hall J, Mostowy S, Aldridge PD, Errington J. Author Correction: Possible role of L-form switching in recurrent urinary tract infection (Nature Communications, (2019), 10, 1, (4379), 10.1038/s41467-019-12359-3). Nature Communications 2019, 10, 5254.