
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
2021
Journal Article
Antibody-dependent enhancement of bacterial disease: prevalence, mechanisms and treatment
Torres, Von Vergel L., Coggon, Carrie F. and Wells, Timothy J. (2021). Antibody-dependent enhancement of bacterial disease: prevalence, mechanisms and treatment. Infection and Immunity, 89 (4) e00054-21, 1-15. doi: 10.1128/IAI.00054-21
2021
Journal Article
Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice
Moentadj, Rabia, Wang, Yiwen, Bowerman, Kate, Rehaume, Linda, Nel, Hendrik, O Cuiv, Paraic, Stephens, Juliette, Baharom, Amalina, Maradana, Muralidhara, Lakis, Vanessa, Morrison, Mark, Wells, Timothy, Hugenholtz, Philip, Benham, Helen, Le Cao, Kim-Anh and Thomas, Ranjeny (2021). Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice. Annals of the Rheumatic Diseases, 80 (5) annrheumdis-2020-219009, annrheumdis-2020. doi: 10.1136/annrheumdis-2020-219009
2020
Journal Article
Structure of dual-BON domain protein DolP identifies phospholipid binding as a new mechanism for protein localization
Bryant, Jack Alfred, Morris, Faye C., Knowles, Timothy J., Maderbocus, Riyaz, Heinz, Eva, Boelter, Gabriela, Alodaini, Dema, Colyer, Adam, Wotherspoon, Peter J., Staunton, Kara A., Jeeves, Mark, Browning, Douglas F., Sevastsyanovich, Yanina R., Wells, Timothy J., Rossiter, Amanda E., Bavro, Vassiliy N., Sridhar, Pooja, Ward, Douglas G., Chong, Zhi-Soon, Goodall, Emily C. A., Icke, Christopher, Teo, Alvin, Chng, Shu-Sin, Roper, David I., Lithgow, Trevor, Cunningham, Adam F., Banzhaf, Manuel, Overduin, Michael and Henderson, Ian R. (2020). Structure of dual-BON domain protein DolP identifies phospholipid binding as a new mechanism for protein localization. eLife, 9 e62614, 1-61. doi: 10.7554/elife.62614
2020
Conference Publication
A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation
Divithotawela, C., Pham, A., Ledger, E. L., Hopkins, P., Tan, M., Yerkovich, S., Wells, T. J. and Chambers, D. C. (2020). A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation. 40th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT), Montreal, Canada, 22-25 April 2020. New York, NY United States: Elsevier.
2020
Conference Publication
A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation
Divithotawela, C., Pham, A., Ledger, E. L., Hopkins, P., Tan, M., Yerkovich, S., Wells, T. J. and Chambers, D. C. (2020). A Novel Pseudomonas aeruginosa Virulence Factor Predicts CLAD and Death after Lung Transplantation. International Society for Heart and Lung Transplantation 40th Annual Meeting and Scientific Sessions, Online, 22 - 25 April 2020. Philadelphia, PA United States: Elsevier. doi: 10.1016/j.healun.2020.01.1265
2020
Journal Article
Treatment of life-threatening Pseudomonas aeruginosa infection by pheresis of inhibitory antibodies
Divithotawela, Chandima, Pham, Amy, Ledger, Emma L., Hopkins, Peter, Wells, Timothy J. and Chambers, Daniel (2020). Treatment of life-threatening Pseudomonas aeruginosa infection by pheresis of inhibitory antibodies. Journal of Heart and Lung Transplantation, 39 (1), 87-89. doi: 10.1016/j.healun.2019.10.001
2019
Journal Article
Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway
Benedikz, Elizabeth K., Bailey, Dalan, Cook, Charlotte N. L., Gonçalves-Carneiro, Daniel, Buckner, Michelle M. C., Blair, Jessica M. A., Wells, Timothy J., Fletcher, Nicola F., Goodall, Margaret, Flores-Langarica, Adriana, Kingsley, Robert A., Madsen, Jens, Teeling, Jessica, Johnston, Sebastian L., MacLennan, Calman A., Balfe, Peter, Henderson, Ian R., Piddock, Laura J. V., Cunningham, Adam F. and McKeating, Jane A. (2019). Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway. Scientific Reports, 9 (1) 7903. doi: 10.1038/s41598-019-44263-7
2018
Journal Article
YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium
Morris, Faye C., Wells, Timothy J., Bryant, Jack A., Schager, Anna E., Sevastsyanovich, Yanina R., Squire, Derrick J. P., Marshall, Jennifer, Isom, Georgia L., Rooke, Jessica, Maderbocus, Riyaz, Knowles, Timothy J., Overduin, Michael, Rossiter, Amanda E., Cunningham, Adam F. and Henderson, Ian R. (2018). YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium. Infection and Immunity, 86 (11) e00829-17. doi: 10.1128/IAI.00829-17
2018
Journal Article
A novel method of serum resistance by Escherichia coli that causes urosepsis
Coggon, Carrie F., Jiang, Andrew, Goh, Kelvin G. K., Henderson, Ian R., Schembri, Mark A. and Wells, Timothy J. (2018). A novel method of serum resistance by Escherichia coli that causes urosepsis. mBio, 9 (3) e00920-18, e00920-18. doi: 10.1128/mbio.00920-18
2018
Journal Article
Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella
Hammarlof, Disa L., Kroger, Carsten, Owen, Sian V., Canals, Rocio, Lacharme-Lora, Lizeth, Wenner, Nicolas, Schager, Anna E., Wells, Timothy J., Henderson, Ian R., Wigley, Paul, Hokamp, Karsten, Feasey, Nicholas A., Gordon, Melita A. and Hinton, Jay C. D. (2018). Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella. Proceedings of the National Academy of Sciences of the United States of America, 115 (11), E2614-E2623. doi: 10.1073/pnas.1714718115
2017
Journal Article
Antigen localization influences the magnitude and kinetics of endogenous adaptive immune response to recombinant Salmonella vaccines
Sevastsyanovich, Yanina R., Withers, David R., Marriott, Claire L., Morris, Faye C., Wells, Timothy J., Browning, Douglas F., Beriotto, Irene, Ross, Ewan, Ali, Hossam Omar, Wardius, Catherine A., Cunningham, Adam F., Henderson, Ian R. and Rossiter, Amanda E. (2017). Antigen localization influences the magnitude and kinetics of endogenous adaptive immune response to recombinant Salmonella vaccines. Infection and Immunity, 85 (12) e00593-17, e00593-17. doi: 10.1128/iai.00593-17
2017
Journal Article
Inactivation of Transcriptional Regulators during Within-Household Evolution of <i>Escherichia coli</i>
Kisiela, Dagmara I., Radey, Matthew, Paul, Sandip, Porter, Stephen, Polukhina, Kseniya, Tchesnokova, Veronika, Shevchenko, Sofiya, Chan, Diana, Aziz, Maliha, Johnson, Timothy J., Price, Lance B., Johnson, James R. and Sokurenko, Evgeni V. (2017). Inactivation of Transcriptional Regulators during Within-Household Evolution of Escherichia coli. Journal of Bacteriology, 199 (13) e00036. doi: 10.1128/JB.00036-17
2017
Conference Publication
Chlamydia-Infected Macrophages: "Trojan Horses" for Dissemination of IL-23 and TNF-Mediated Inflammation in SKG Mouse Reactive Arthritis
Baillet, Athan, Bhuyan, Zaied Ahmed, Douillard, Claire, Bozon, Aurelie, Armitage, Charles, Romand, Xavier, Minh Vu Chuong Nguyen,, Favier, Bertrand, Wells, Timothy, Beagley, Kenneth and Thomas, Ranjeny (2017). Chlamydia-Infected Macrophages: "Trojan Horses" for Dissemination of IL-23 and TNF-Mediated Inflammation in SKG Mouse Reactive Arthritis. 2017 ACR/ARHP Pediatric Rheumatology Symposium, San Diego, CA, United States, 3-8 November 2017. Hoboken, NJ, United States: John Wiley & Sons.
2016
Journal Article
Captivity humanizes the primate microbiome
Clayton, Jonathan B., Vangay, Pajau, Hu Huang, , Ward, Tonya, Hillmann, Benjamin M., Al-Ghalith, Gabriel A., Travis, Dominic A., Ha Thang Long, , Bui Van Tuan, , Vo Van Minh, , Cabana, Francis, Nadler, Tilo, Toddes, Barbara, Murphy, Tami, Glander, Kenneth E., Johnson, Timothy J. and Knights, Dan (2016). Captivity humanizes the primate microbiome. Proceedings of the National Academy of Sciences of the United States of America, 113 (37), 10376-10381. doi: 10.1073/pnas.1521835113
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
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
Funding
Current funding
Past funding
Supervision
Availability
- Associate Professor Timothy Wells is:
- Available for supervision
Before you email them, read our advice on how to contact 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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Master Philosophy
Antibody-mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds
Principal Advisor
Other advisors: Professor Kiarash Khosrotehrani
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Doctor Philosophy
The impact of helpful and harmful immune responses on infection in the cystic fibrosis lung
Principal Advisor
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Doctor Philosophy
The role of Two Partner Secretion proteins in the virulence of Pseudomonas aeruginosa
Principal Advisor
Other advisors: Professor Ian Henderson, Dr Jessica Rooke
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Doctor Philosophy
Investigating Pseudomonas aeruginosa persistance in the cystic fibrosis lung
Principal Advisor
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Doctor Philosophy
Investigating the gram-negative bacterial and host factors that drive sepsis outcomes
Principal Advisor
Other advisors: Dr Kate McCarthy
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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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Master Philosophy
Antibody mediated exacerbation of Pseudomonas aeruginosa infected chronic wounds
Principal Advisor
Other advisors: Professor Kiarash Khosrotehrani
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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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Doctor Philosophy
Investigating Pseudomonas aeruginosa persistance in the cystic fibrosis lung
Principal Advisor
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Doctor Philosophy
The role of cloaking antibodies in the pathophysiology, diagnosis, and treatment of inflammatory diseases
Principal Advisor
Other advisors: Professor Mark Morrison
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Doctor Philosophy
Investigating Pseudomonas aeruginosa persistence in the cystic fibrosis lung
Principal Advisor
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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
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Doctor Philosophy
Investigating B cell responses to Pseudomonas O-Antigen
Principal Advisor
Other advisors: Professor Ian Henderson
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Doctor Philosophy
Characterisation of the anti-mycobacterial activity of wollamide cyclic hexapeptides against Mycobacterium tuberculosis
Associate Advisor
Other advisors: Professor Antje Blumenthal
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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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Doctor Philosophy
The role of endoplasmic reticulum stress in spondyloarthropathy
Associate Advisor
Other advisors: Professor Ranjeny Thomas, Dr Anne-Sophie Bergot
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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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Doctor Philosophy
Deciphering the protective program of innate and adaptive cells in pathogen infection
Associate Advisor
Other advisors: Professor Gabrielle Belz
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Doctor Philosophy
High Mobility Group Box Family Member TOX2 in Innate Lymphoid Cell Development and Maintenance
Associate Advisor
Other advisors: Professor Gabrielle Belz
Completed supervision
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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
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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