Overview
Background
Dr Timothy Wells joined the Frazer Institute in 2016 as a Senior Research Fellow. His research aims to find novel methods of treating multi-drug resistant bacteria, by examing the interactions between the host immune system and Gram negative bacteria. His research largely focuses on Pseudomonas aeruginosa acute and chronic infections, espeically in people living with cystic fibrosis. Dr Wells is passionate about making his research as clinically relevant as possible, with his work previously having led to novel treatment of critically ill patients. His research uses a mixture of molecular microbiology, immunology and genomic approaches.
Availability
- Associate Professor Timothy Wells is:
- Available for supervision
- Media expert
Qualifications
- Bachelor (Honours) of Biotechnology, The University of Queensland
- Doctor of Philosophy, The University of Queensland
Research interests
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Pseudomonas aeruginosa
The T-Wells lab is interested in all infections by Pseudomonas aeruginosa whether that be chronic lung infection, wound and joint infections, acute pneumonia, UTIs and bacteremia.
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Bacterial chronic lung infections
The T-Wells lab is interested in bacterial infections in people with cystic fibrosis, bronchiectasis, COPD and post-lung transplant
Research impacts
Dr Wells’s original work in the field of host- pathogen interactions during chronic lung infection has led to several key insights and direct translation to the clinic.
Antibody dependent enhancement of bacterial infection: Antibodies usually protect against bacterial infection, however Dr Wells' work has identified ‘cloaking antibodies’ in patients who have Pseudomonas aeruginosa infections. Cloaking antibodies paradoxically prevent immune killing of patient's bacterial strains. Importantly, high titres of cloaking antibodies has been associated with worse lung function and patient outcomes in people with cystic fibrosis, bronchiectasis and post-lung transplant. These antibodies are also prevelant in actue Pseduomonas infections such as bacteremia.
Novel treatment of multi-drug resistant Pseudomonas aeruginosa lung infection: As cloaking antibodies (cAbs) protect bacteria from immune killing, we hypothesised that cAb removal would restore normal immune killing. Three patients with chronic P. aeruginosa infections and cAb, who had exhausted all standard treatment options have now been treated via plasmapheresis. This treatment removes all antibody, including cAbs from the patients. After treatment, P. aeruginosa was undetectable in all patients, inflammatory markers were normal and lung function increased. As these patients had strains displaying resistance to many antibiotics used clinically, this is a novel treatment method for multi-drug resistant infections.
Works
Search Professor Timothy Wells’s works on UQ eSpace
2016
Journal Article
Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies
Gohl, Daryl M., Vangay, Pajau, Garbe, John, MacLean, Allison, Hauge, Adam, Becker, Aaron, Gould, Trevor J., Clayton, Jonathan B., Johnson, Timothy J., Hunter, Ryan, Knights, Dan and Beckman, Kenneth B. (2016). Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies. Nature Biotechnology, 34 (9), 942-+. doi: 10.1038/nbt.3601
2016
Journal Article
Evolutionary History of the Global Emergence of the <i>Escherichia coli</i> Epidemic Clone ST131
Stoesser, Nicole, Sheppard, Anna E., Pankhurst, Louise, De Maio, Nicola, Moore, Catrin E., Sebra, Robert, Turner, Paul, Anson, Luke W., Kasarskis, Andrew, Batty, Elizabeth M., Kos, Veronica, Wilson, Daniel J., Phetsouvanh, Rattanaphone, Wyllie, David, Sokurenko, Evgeni, Manges, Amee R., Johnson, Timothy J., Price, Lance B., Peto, Timothy E. A., Johnson, James R., Didelot, Xavier, Walker, A. Sarah and Crook, Derrick W. (2016). Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131. Mbio, 7 (2) e02162-15. doi: 10.1128/mBio.02162-15
2015
Journal Article
Genome analysis and <i>in vivo</i> virulence of porcine extraintestinal pathogenic <i>Escherichia coli</i> strain PCN033
Liu, Canying, Zheng, Huajun, Yang, Minjun, Xu, Zhuofei, Wang, Xiangru, Wei, Liuya, Tang, Biao, Liu, Feng, Zhang, Yanyan, Ding, Yi, Tang, Xibiao, Wu, Bin, Johnson, Timothy J., Chen, Huanchun and Tan, Chen (2015). Genome analysis and in vivo virulence of porcine extraintestinal pathogenic Escherichia coli strain PCN033. Bmc Genomics, 16 717. doi: 10.1186/s12864-015-1890-9
2015
Journal Article
Cross-species chimeras reveal BamA POTRA and β-barrel domains must be fine-tuned for efficient OMP insertion
Browning, Douglas F., Bavro, Vassiliy N., Mason, Jessica L., Sevastsyanovich, Yanina R., Rossiter, Amanda E., Jeeves, Mark, Wells, Timothy J., Knowles, Timothy J., Cunningham, Adam F., Donald, James W., Palmer, Tracy, Overduin, Michael and Henderson, Ian R. (2015). Cross-species chimeras reveal BamA POTRA and β-barrel domains must be fine-tuned for efficient OMP insertion. Molecular Microbiology, 97 (4), 646-659. doi: 10.1111/mmi.13052
2014
Journal Article
Chaperone-usher fimbriae in a diverse selection of <i>Gallibacterium</i> genomes
Kudirkiene, Egle, Bager, Ragnhild J., Johnson, Timothy J. and Bojesen, Anders M. (2014). Chaperone-usher fimbriae in a diverse selection of Gallibacterium genomes. Bmc Genomics, 15 1093. doi: 10.1186/1471-2164-15-1093
2014
Journal Article
Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing
Wells, Timothy J., Whitters, Deborah, Sevastsyanovich, Yanina R., Heath, Jennifer N., Pravin, John, Goodall, Margaret, Browning, Douglas F., O'Shea, Matthew K., Cranston, Amy, De Soyza, Anthony, Cunningham, Adam F., MacLennan, Calman A., Henderson, Ian R. and Stockley, Robert A. (2014). Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing. Journal of Experimental Medicine, 211 (9), 1893-1904. doi: 10.1084/jem.20132444
2014
Journal Article
Effects of tylosin administration on C-reactive protein concentration and carriage of <i>Salmonella enterica</i> in pigs
Kim, Hyeun Bum, Singer, Randall S., Borewicz, Klaudyna, White, Bryan A., Sreevatsan, Srinand, Johnson, Timothy J., Espejo, Luis A. and Isaacson, Richard E. (2014). Effects of tylosin administration on C-reactive protein concentration and carriage of Salmonella enterica in pigs. American Journal of Veterinary Research, 75 (5), 460-467. doi: 10.2460/ajvr.75.5.460
2013
Journal Article
Mutational and topological analysis of the Escherichia coli BamA protein
Browning, Douglas F., Matthews, Sophie A., Rossiter, Amanda E., Sevastsyanovich, Yanina R., Jeeves, Mark, Mason, Jessica L., Wells, Timothy J., Wardius, Catherine A., Knowles, Timothy J., Cunningham, Adam F., Bavro, Vassiliy N., Overduin, Michael and Henderson, Ian R. (2013). Mutational and topological analysis of the Escherichia coli BamA protein. PLoS ONE, 8 (12) e84512, e84512. doi: 10.1371/journal.pone.0084512
2013
Journal Article
Genotypic and phenotypic characterisation of enteroaggregative Escherichia coli from children in Rio de Janeiro, Brazil
Franca, Fernanda L. S., Wells, Timothy J., Browning, Douglas F., Nogueira, Raquel Tayar, Sarges, Felipe Silva, Pereira, Ana Claudia, Cunningham, Adam F., Lucheze, Kely, Paula Rosa, Ana Claudia, Henderson, Ian R. and de Luna, Maria das Gracas (2013). Genotypic and phenotypic characterisation of enteroaggregative Escherichia coli from children in Rio de Janeiro, Brazil. PLoS ONE, 8 (7) e69971, e69971. doi: 10.1371/journal.pone.0069971
2013
Journal Article
Laboratory adapted Escherichia coli K-12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis
Browning, Douglas F., Wells, Timothy J., Franca, Fernanda L. S., Morris, Faye C., Sevastsyanovich, Yanina R., Bryant, Jack A., Johnson, Matthew D., Lund, Peter A., Cunningham, Adam F., Hobman, Jon L., May, Robin C., Webber, Mark A. and Henderson, Ian R. (2013). Laboratory adapted Escherichia coli K-12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis. Molecular Microbiology, 87 (5), 939-950. doi: 10.1111/mmi.12144
2013
Book Chapter
Type 1 and 5 secretion systems and associated toxins
Wells, Timothy J. and Henderson, Ian R. (2013). Type 1 and 5 secretion systems and associated toxins. Escherichia coli: pathotypes and principles of pathogenesis. (pp. 499-532) edited by Michael S. Donnenberg. Cambridge, MA, United States: Academic Press. doi: 10.1016/B978-0-12-397048-0.00016-4
2012
Journal Article
Expansion of the IncX plasmid family for improved identification and typing of novel plasmids in drug-resistant <i>Enterobacteriaceae</i>
Johnson, Timothy J., Bielak, Eliza M., Fortini, Daniela, Hansen, Lars Hestbjerg, Hasman, Henrik, Debroy, Chitrita, Nolan, Lisa K. and Carattoli, Alessandra (2012). Expansion of the IncX plasmid family for improved identification and typing of novel plasmids in drug-resistant Enterobacteriaceae. Plasmid, 68 (1), 43-50. doi: 10.1016/j.plasmid.2012.03.001
2012
Journal Article
A generalised module for the selective extracellular accumulation of recombinant proteins
Sevastsyanovich, Yanina R., Leyton, Denisse L., Wells, Timothy J., Wardius, Catherine A., Tveen-Jensen, Karina, Morris, Faye C., Knowles, Timothy J., Cunningham, Adam F., Cole, Jeffrey A. and Henderson, Ian R. (2012). A generalised module for the selective extracellular accumulation of recombinant proteins. Microbial Cell Factories, 11 (69) 69. doi: 10.1186/1475-2859-11-69
2012
Journal Article
Discovery of an archetypal protein transport system in bacterial outer membranes
Selkrig, Joel, Mosbahi, Khedidja, Webb, Chaille T., Belousoff, Matthew J., Perry, Andrew J., Wells, Timothy J., Morris, Faye, Leyton, Denisse L., Totsika, Makrina, Phan, Minh-Duy, Celik, Nermin, Kelly, Michelle, Oates, Clare, Hartland, Elizabeth L., Robins-Browne, Roy M., Ramarathinam, Sri Harsha, Purcell, Anthony W., Schembri, Mark A., Strugnell, Richard A., Henderson, Ian R., Walker, Daniel and Lithgow, Trevor (2012). Discovery of an archetypal protein transport system in bacterial outer membranes. Nature Structural and Molecular Biology, 19 (5), 506-510. doi: 10.1038/nsmb.2261
2012
Journal Article
Molecular characterization of the EhaG and UpaG trimeric autotransporter proteins from pathogenic Escherichia coli
Totsika, Makrina, Wells, Timothy J., Beloin, Christophe, Valle, Jaione, Allsopp, Luke P., King, Nathan P., Ghigo, Jean-Marc and Schembri, Mark A. (2012). Molecular characterization of the EhaG and UpaG trimeric autotransporter proteins from pathogenic Escherichia coli. Applied and Environmental Microbiology, 78 (7), 2179-2189. doi: 10.1128/AEM.06680-11
2011
Journal Article
Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins
Leyton, Denisse L., Sevastsyanovich, Yanina R., Browning, Douglas F., Rossiter, Amanda E., Wells, Timothy J., Fitzpatrick, Rebecca E., Overduin, Michael, Cunningham, Adam F. and Henderson, Ian R. (2011). Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins. Journal of Biological Chemistry, 286 (49), 42283-42291. doi: 10.1074/jbc.M111.306118
2011
Journal Article
SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection
Raghunathan, Dhaarini, Wells, Timothy J., Morris, Faye C., Shaw, Robert K., Bobat, Saeeda, Peters, Sarah E., Paterson, Gavin K., Jensen, Karina Tveen, Leyton, Denisse L., Blair, Jessica M. A., Browning, Douglas F., Pravin, John, Flores-Langarica, Adriana, Hitchcock, Jessica R., Moraes, Claudia T. P., Piazza, Roxane M. F., Maskell, Duncan J., Webber, Mark A., May, Robin C., MacLennan, Calman A., Piddock, Laura J., Cunningham, Adam F. and Henderson, Ian R. (2011). SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection. Infection and Immunity, 79 (11), 4342-4352. doi: 10.1128/IAI.05592-11
2011
Journal Article
Spleen transcriptome response to infection with avian pathogenic <i>Escherichia coli</i> in broiler chickens
Sandford, Erin E., Orr, Megan, Balfanz, Emma, Bowerman, Nate, Li, Xianyao, Zhou, Huaijun, Johnson, Timothy J., Kariyawasam, Subhashinie, Liu, Peng, Nolan, Lisa K. and Lamont, Susan J. (2011). Spleen transcriptome response to infection with avian pathogenic Escherichia coli in broiler chickens. Bmc Genomics, 12 469. doi: 10.1186/1471-2164-12-469
2011
Journal Article
Comparative Genomics of Multidrug Resistance-Encoding IncA/C Plasmids from Commensal and Pathogenic <i>Escherichia coli</i> from Multiple Animal Sources
Fernandez-Alarcon, Claudia, Singer, Randall S. and Johnson, Timothy J. (2011). Comparative Genomics of Multidrug Resistance-Encoding IncA/C Plasmids from Commensal and Pathogenic Escherichia coli from Multiple Animal Sources. Plos One, 6 (8) e23415. doi: 10.1371/journal.pone.0023415
2011
Journal Article
Complete Genome Sequence of <i>Gallibacterium anatis</i> Strain UMN179, Isolated from a Laying Hen with Peritonitis
Johnson, Timothy J., Fernandez-Alarcon, Claudia, Bojesen, Anders Miki, Nolan, Lisa K., Trampel, Darrell W. and Seemann, Torsten (2011). Complete Genome Sequence of Gallibacterium anatis Strain UMN179, Isolated from a Laying Hen with Peritonitis. Journal of Bacteriology, 193 (14), 3676-3677. doi: 10.1128/JB.05177-11
Funding
Current funding
Past funding
Supervision
Availability
- Associate Professor Timothy Wells is:
- Available for supervision
Looking for a supervisor? Read our advice on how to choose a supervisor.
Available projects
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Synergistic drugs to counteract cloaking antibodies
Some patients infected with P. aeruginosa produce antibodies that, instead of fighting infection, actively protect P. aeruginosa from killing by the immune system. These ‘cloaking antibodies’ (cAb) target a lipopolysaccharide on the bacterial surface, known as O-antigen and form a physical barrier that stops the membrane attack complex (MAC) from reaching the bacterial outer membrane. Importantly, patients with cAb had greater disease severity and worse outcomes than patients with no cAb. Previous treatment for cAbs has focused on removal of the antibody, however a second attractive target is the infecting bacteria itself. We have recently investigated the bacterial requirements for the cloaking phenotype by creating strains with variable amounts and lengths of O-antigen expression. Serum bactericidal assays revealed that the serum-inhibition phenotype requires long and dense O-antigen We hypothesise that existing bacterial outer membrane modifying drugs can overcome the effect of cAbs, without cAb removal. This project will investigate potential synergistic drugs that could counteract cAbs, leading to bacterial killing.
Supervision history
Current supervision
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Doctor Philosophy
Pseudomonas aeruginosa Pathogenesis Mechanisms in Bacteraemia and Infective Endocarditis
Principal Advisor
Other advisors: Dr Kate McCarthy
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Doctor Philosophy
The role of cloaking antibodies in the pathophysiology and diagnosis of Crohn's Disease
Principal Advisor
Other advisors: Professor Mark Morrison
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Doctor Philosophy
Targeting the outer membrane of Pseudomonas aeruginosa to disrupt the action of cloaking antibodies in cystic fibrosis
Principal Advisor
Completed supervision
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2025
Doctor Philosophy
The Role of PlpD in the Virulence of P. aeruginosa
Principal Advisor
Other advisors: Professor Ian Henderson, Dr Jessica Rooke
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2025
Master Philosophy
Antibody-mediated exacerbation of chronic wounds colonised with Pseudomonas aeruginosa
Principal Advisor
Other advisors: Professor Kiarash Khosrotehrani
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2025
Doctor Philosophy
Improving Plasmapheresis: Investigating specific removal of cloaking antibodies to treat Pseudomonas aeruginosa
Principal Advisor
Other advisors: Professor Ian Henderson
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2025
Doctor Philosophy
Investigating Pseudomonas aeruginosa persistence in the cystic fibrosis lung
Principal Advisor
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2023
Doctor Philosophy
Antibody-Dependent Serum Resistance of Intractable Lung Bacteria
Principal Advisor
Other advisors: Professor Dan Chambers
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2021
Doctor Philosophy
Mechanisms Underpinning Antibody-Mediated Serum Resistance of Gram-Negative Bacteria
Principal Advisor
Other advisors: Professor Mark Morrison
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2025
Doctor Philosophy
High mobility group box family member TOX2 in innate lymphoid cell development and maintenance
Associate Advisor
Other advisors: Professor Gabrielle Belz
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2025
Doctor Philosophy
The Role of Endoplasmic Reticulum Stress in Autoimmune Inflammatory Arthritis
Associate Advisor
Other advisors: Professor Ranjeny Thomas, Dr Anne-Sophie Bergot
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2024
Doctor Philosophy
Characterisation of the anti-mycobacterial activity of wollamide cyclic hexapeptides against Mycobacterium tuberculo sis
Associate Advisor
Other advisors: Professor Antje Blumenthal
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2023
Doctor Philosophy
Investigating immunosuppression and immunotherapy in bacterial infection
Associate Advisor
Other advisors: Associate Professor Fernando Guimaraes
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2023
Doctor Philosophy
Immune functions of WNT production and signalling in the host response to infection with pathogenic E. coli.
Associate Advisor
Other advisors: Dr Janin Chandra, Professor Antje Blumenthal
Media
Enquiries
Contact Associate Professor Timothy Wells directly for media enquiries about:
- cystic fibrosis infections
- Pseudomonas aeruginosa
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