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
- Dr 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
Featured
2017
Journal Article
The Use of Plasmapheresis in Patients with Bronchiectasis with Pseudomonas aeruginosa Infection and Inhibitory Antibodies
Wells, Timothy J., Davison, John, Sheehan, Emma, Kanagasundaram, Suren, Spickett, Gavin, MacLennan, Calman A., Stockley, Robert A., Cunningham, Adam F., Henderson, Ian R. and De Soyza, Anthony (2017). The Use of Plasmapheresis in Patients with Bronchiectasis with Pseudomonas aeruginosa Infection and Inhibitory Antibodies. American Journal of Respiratory and Critical Care Medicine, 195 (7), 955-958. doi: 10.1164/rccm.201603-0599LE
2024
Journal Article
Dichotomous outcomes of TNFR1 and TNFR2 signaling in NK cell-mediated immune responses during inflammation
McCulloch, Timothy R., Rossi, Gustavo R., Alim, Louisa, Lam, Pui Yeng, Wong, Joshua K. M., Coleborn, Elaina, Kumari, Snehlata, Keane, Colm, Kueh, Andrew J., Herold, Marco J., Wilhelm, Christoph, Knolle, Percy A., Kane, Lawrence, Wells, Timothy J. and Souza-Fonseca-Guimaraes, Fernando (2024). Dichotomous outcomes of TNFR1 and TNFR2 signaling in NK cell-mediated immune responses during inflammation. Nature Communications, 15 (1) 9871, 9871. doi: 10.1038/s41467-024-54232-y
2024
Journal Article
Complete genome sequences of eight <i>Pasteurella multocida</i> isolates representing all lipopolysaccharide outer core loci
Hashish, Amro, Johnson, Timothy J., Ghanem, Mostafa, Sato, Yuko, Macedo, Nubia R., LeCount, Karen J. and El-Gazzar, Mohamed (2024). Complete genome sequences of eight Pasteurella multocida isolates representing all lipopolysaccharide outer core loci. Microbiology Resource Announcements, 13 (11). doi: 10.1128/mra.00604-24
2024
Journal Article
Type 5 secretion system antigens as vaccines against Gram-negative bacterial infections
Da Costa, Rochelle M., Rooke, Jessica L., Wells, Timothy J., Cunningham, Adam F. and Henderson, Ian R. (2024). Type 5 secretion system antigens as vaccines against Gram-negative bacterial infections. npj Vaccines, 9 (1) 159, 159. doi: 10.1038/s41541-024-00953-6
2024
Journal Article
Cloaking antibodies are prevalent in Burkholderia cepacia complex infection and their removal restores serum killing
Pham, Amy, Tan, Kellynn K. Y., Ledger, Emma L., Smith, Daniel J., Reid, David W., Burr, Lucy, Chambers, Daniel C. and Wells, Timothy J. (2024). Cloaking antibodies are prevalent in Burkholderia cepacia complex infection and their removal restores serum killing. Frontiers in Cellular and Infection Microbiology, 14 1426773. doi: 10.3389/fcimb.2024.1426773
2024
Journal Article
Mechanisms of antibody-dependent enhancement of infectious disease
Wells, Timothy J., Esposito, Tyron, Henderson, Ian R. and Labzin, Larisa I. (2024). Mechanisms of antibody-dependent enhancement of infectious disease. Nature Reviews Immunology. doi: 10.1038/s41577-024-01067-9
2024
Conference Publication
Does a leopard change its spots? Pseudomonas aeruginosa in cystic fibrosis after CFTR modulation
Ledger, Emma, Smith, Daniel, Teh, Jing Jie, Wood, Michelle, Whibley, Page, Morrison, Mark, Goldberg, Joanna, Reid, David and Wells, Timothy (2024). Does a leopard change its spots? Pseudomonas aeruginosa in cystic fibrosis after CFTR modulation. Abstracts of the 15th Australasian Cystic Fibrosis Conference, Brisbane, QLD, Australia, 2–4 August 2024. Richmond, VIC, Australia: John Wiley & Sons.
2024
Journal Article
The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy
McCulloch, Timothy R., Rossi, Gustavo R., Miranda‐Hernandez, Socorro, Valencia‐Hernandez, Ana Maria, Alim, Louisa, Belle, Clemence J., Krause, Andrew, Zacchi, Lucia F., Lam, Pui Yeng, Nakamura, Kyohei, Kupz, Andreas, Wells, Timothy J. and Souza‐Fonseca‐Guimaraes, Fernando (2024). The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy. Immunology and Cell Biology, 102 (8), 721-733. doi: 10.1111/imcb.12794
2024
Journal Article
Impact of CFTR modulation on Pseudomonas aeruginosa infection in people with cystic fibrosis
Ledger, Emma L., Smith, Daniel J., Teh, Jing Jie, Wood, Michelle E., Whibley, Page E., Morrison, Mark, Goldberg, Joanna B., Reid, David W. and Wells, Timothy J. (2024). Impact of CFTR modulation on Pseudomonas aeruginosa infection in people with cystic fibrosis. The Journal of Infectious Diseases, 230 (3), e536-e547. doi: 10.1093/infdis/jiae051
2024
Journal Article
Antibody-mediated serum resistance protects Pseudomonas aeruginosa during bloodstream infections
Hickson, Sarah M., Hoehensteiger, Johannes K., Mayer-Coverdale, Johanna, Torres, Von Vergel L., Feng, Wenkang, Monteith, Joshua N., Henderson, Ian R., McCarthy, Kate L. and Wells, Timothy J. (2024). Antibody-mediated serum resistance protects Pseudomonas aeruginosa during bloodstream infections. The Journal of Infectious Diseases, 230 (2), e221-e229. doi: 10.1093/infdis/jiad457
2023
Journal Article
Genomic analyses of Burkholderia respiratory isolates indicates two evolutionarily distinct B. anthina clades
Pham, Amy, Volmer, James G., Chambers, Daniel C., Smith, Daniel J., Reid, David W., Burr, Lucy and Wells, Timothy J. (2023). Genomic analyses of Burkholderia respiratory isolates indicates two evolutionarily distinct B. anthina clades. Frontiers in Microbiology, 14 1274280, 1-14. doi: 10.3389/fmicb.2023.1274280
2023
Conference Publication
Goblet cell specific anti-apoptotic role of interleukin-24 in spondyloarthritis-associated ileitis
Cameron, A., Giri, R., Begun, J., Wells, T., Bergot, A. S. and Thomas, R. (2023). Goblet cell specific anti-apoptotic role of interleukin-24 in spondyloarthritis-associated ileitis. EULAR 2023 European Congress of Rheumatology, Milan, Italy, 31 May-3 June 2023. London, United Kingdom: BMJ Group. doi: 10.1136/annrheumdis-2023-eular.1346
2023
Journal Article
Differential regulation of natural killer cells by tumor necrosis factor receptors 1 and 2
McCulloch, Timothy R., Rossi, Gustavo Rodrigues, Lam, Allie, Wong, Joshua, Kane, Lawrence P, Herold, Marco, Wells, Timothy and Souza-Fonseca-Guimaraes, Fernando (2023). Differential regulation of natural killer cells by tumor necrosis factor receptors 1 and 2. The Journal of Immunology, 210 (S1), 72.28-72.28. doi: 10.4049/jimmunol.210.supp.72.28
2023
Conference Publication
TIGIT limits anti-bacterial immunity and is a potential target for immunotherapy
Souza-Fonseca-Guimaraes, Fernando, Rossi, Gustavo Rodrigues, Wells, Timothy and McCulloch, Timothy Ryan (2023). TIGIT limits anti-bacterial immunity and is a potential target for immunotherapy. IMMUNOLOGY2023™ Meeting, Washington, DC, United States, 11 - 15 May 2023. Rockville, MD, United States: The American Association of Immunologists. doi: 10.4049/jimmunol.210.supp.64.14
2023
Journal Article
IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study
Shojaei, Maryam, Shamshirian, Amir, Monkman, James, Grice, Laura, Tran, Minh, Tan, Chin Wee, Teo, Siok Min, Rodrigues Rossi, Gustavo, McCulloch, Timothy R., Nalos, Marek, Raei, Maedeh, Razavi, Alireza, Ghasemian, Roya, Gheibi, Mobina, Roozbeh, Fatemeh, Sly, Peter D., Spann, Kirsten M., Chew, Keng Yih, Zhu, Yanshan, Xia, Yao, Wells, Timothy J., Senegaglia, Alexandra Cristina, Kuniyoshi, Carmen Lúcia, Franck, Claudio Luciano, dos Santos, Anna Flavia Ribeiro, Noronha, Lucia de, Motamen, Sepideh, Valadan, Reza, Amjadi, Omolbanin ... Tang, Benjamin (2023). IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study. Frontiers in Immunology, 13 1060438, 1-14. doi: 10.3389/fimmu.2022.1060438
2022
Journal Article
CIS and TGF ‐β regulatory pathways influence immunity to bacterial infection
McCulloch, Timothy R., Rossi, Gustavo R., Schreuder, Jaring, Belz, Gabrielle T., Wells, Timothy J. and Souza‐Fonseca‐Guimaraes, Fernando (2022). CIS and TGF ‐β regulatory pathways influence immunity to bacterial infection. Immunology, 167 (1), 54-63. doi: 10.1111/imm.13516
2022
Journal Article
Genomic diversity and antimicrobial resistance of Prevotella species isolated from chronic lung disease airways
Webb, Kasey A., Olagoke, Olusola, Baird, Timothy, Neill, Jane, Pham, Amy, Wells, Timothy J., Ramsay, Kay A., Bell, Scott C., Sarovich, Derek S. and Price, Erin P. (2022). Genomic diversity and antimicrobial resistance of Prevotella species isolated from chronic lung disease airways. Microbial Genomics, 8 (2) 000754. doi: 10.1099/mgen.0.000754
2022
Journal Article
Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
Tran, Thao Thanh, Mathmann, Carmen D., Gatica-Andrades, Marcela, Rollo, Rachel F., Oelker, Melanie, Ljungberg, Johanna K., Nguyen, Tam T. K., Zamoshnikova, Alina, Kummari, Lalith K., Wyer, Orry J. K., Irvine, Katharine M., Melo-Bolívar, Javier, Gross, Annette, Brown, Darren, Mak, Jeffrey Y. W., Fairlie, David P., Hansford, Karl A., Cooper, Matthew A., Giri, Rabina, Schreiber, Veronika, Joseph, Shannon R., Simpson, Fiona, Barnett, Timothy C., Johansson, Jörgen, Dankers, Wendy, Harris, James, Wells, Timothy J., Kapetanovic, Ronan, Sweet, Matthew J. ... Blumenthal, Antje (2022). Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages. PLoS Pathogens, 18 (1) e1010166, e1010166. doi: 10.1371/journal.ppat.1010166
2021
Journal Article
Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibodies
Divithotawela, Chandima, Pham, Amy, Bell, Peter T., Ledger, Emma L., Tan, Maxine, Yerkovich, Stephanie, Grant, Michelle, Hopkins, Peter M., Wells, Timothy J. and Chambers, Daniel C. (2021). Inferior outcomes in lung transplant recipients with serum Pseudomonas aeruginosa specific cloaking antibodies. The Journal of Heart and Lung Transplantation, 40 (9), 951-959. doi: 10.1016/j.healun.2021.05.016
2021
Journal Article
Anti-LPS IgA and IgG can inhibit serum killing of Pseudomonas aeruginosa in patients with cystic fibrosis
Pham, Amy, Ledger, Emma L., Coggon, Carrie F., Henderson, Ian R., Reid, David W., Bell, Scott C., Smith, Daniel J. and Wells, Timothy J. (2021). Anti-LPS IgA and IgG can inhibit serum killing of Pseudomonas aeruginosa in patients with cystic fibrosis. Infection and Immunity, 89 (12) e00412-21, e0041221. doi: 10.1128/iai.00412-21
Funding
Current funding
Past funding
Supervision
Availability
- Dr Timothy Wells is:
- Available for supervision
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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
The impact of helpful and harmful immune responses on infection in the cystic fibrosis lung
Principal Advisor
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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
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
Investigating Pseudomonas aeruginosa persistance 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 B cell responses to Pseudomonas O-Antigen
Principal Advisor
Other advisors: Professor Ian Henderson
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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 persistance in the cystic fibrosis lung
Principal Advisor
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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
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
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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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
Completed supervision
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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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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 Dr Timothy Wells directly for media enquiries about:
- cystic fibrosis infections
- Pseudomonas aeruginosa
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