Assoc Prof Dena Lyras - Researcher Profile

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Address

Department of Microbiology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Biography

A superbug of our own creation

The rapid evolution of bacteria and the excessive use of antibiotics have turned our hospitals from institutions of healing to incubators of new breeds of superbugs. The challenge for researchers such as Dr Dena Lyras is to uncover the secrets and weaknesses of bacteria that are changing before their eyes.

Dena has spent her research career developing world-leading knowledge of the bacterium Clostridium difficile, a gut bacterium that causes disease in the intestines. The bacterium usually attacks hospital patients that are being treated with antibiotics for other, unrelated, infections. 

Over the past decade the bug has undergone a radical evolution that has allowed it to thrive in hospital environments and develop into the leading cause of death from hospital-acquired antibiotic associated intestinal infection.

Clostridium difficile has become so successful at exploiting our modern hospital practices that it is now found in every hospital in the world that uses antibiotics. And not only is the bactrium surviving medical science's best attempts to kill it, it is actually becoming more deadly.

"I'm interested in this bacterium because it has adapted so well to our modern hospital environments. It is really a product of our times," Dena says.

"It was not known to cause problems before antibiotics, but the introduction of antibiotics changed things and it found a new niche to occupy. As a consequence it has become a significant problem in hospitals worldwide.

"It has also changed genetically and now causes more severe disease. Where people would normally be treated and recover, now we have people who are far sicker, and more people are dying because they cannot recover from these infections.

"The reason for this is that the bacteria quickly adapt to the environment they are in – in this case hospitals – resulting in newer versions of the bacteria that are far better at causing disease. In other words, superbugs. I am interested in how that process happens."

Researchers in Dena's lab, the Clostridial Genetics Laboratory, are trying to understand how Clostridium difficile causes disease, and in particular why these new versions of the bacterium have become more potent.

Part of the bug's success lies in the use of antibiotics in hospitals. Not only have the bacteria developed increasing resistance to antibiotic treatments, but the devastating effect some drugs have on the good bacteria that protect our bodies is creating a space that harmful bacteria can exploit.

Dena's team have enjoyed some success in better understanding the bug through genetic manipulation. She was the lead author of a study published in the prestigious journal Nature, which shed new light on the essential role specific toxins play in causing disease, a discovery that disproved prevailing opinion.

More recently, Dena's team have discovered new genetic factors responsible for creating the increased virulence of the bacteria in research that has recently been accepted for publication in another prestigious journal.

Dena is now using this knowledge to develop new therapeutic strategies capable of tackling the ever-changing super bug. She heads an ARC Linkage project in collaboration with industry partners who are developing strategies for handling these infections.

But there are no promises of an easy fix.

"We think of these bacteria as lacking complexity, but when we see what they can do we see that they are incredibly complex and can change at a frighteningly fast rate," Dena says.

Qualifications

PHD
Institution: La Trobe University
Year awarded: 2005

Publications

Book Chapters

Carter, G.P., Lyras, D., Poon, R., Howarth, P., Rood, J.I., 2010, Methods for gene cloning and targeted mutagenesis, in Methods in Molecular Biology - Clostridium difficile: Methods and Protocols, eds Peter Mullany and Adam P Roberts, Humana Press, UK, pp. 183-201.

Lyras, D., Rood, J.I., 2006, Clostridial genetics, in Gram-Positive Pathogens, eds Vincent A Fischetti, Richard P Novick, Joseph J Ferretti, Daniel A Portnoy, Julian I Rood, ASM Press, USA, pp. 672-687.

Lyras, D., Rood, J.I., 2005, Transposable genetic elements of Clostridia, in Handbook on Clostridia, eds Peter Duerre, CRC Press, Boca Raton USA, pp. 631-643.

Lyras, D., Rood, J.I., 2000, Clostridial genetics, in Gram-positive pathogens, ASM Press, Washington USA, pp. 529-539.

Lyras, D., Rood, J.I., 1997, Transposable genetic elements and antibiotic resistance determinants from Clostridium perfringens and Clostridium difficile, in The clostridia: molecular biology and pathogenesis, Academic Press Limited, London UK, pp. 73-92.

Journal Articles

Porter, C.J., Bantwal, R., Bannam, T.L., Rosado, C.J., Pearce, M.C., Adams, V.M., Lyras, D., Whisstock, J.C., Rood, J.I., 2012, The conjugation protein TcpC from Clostridium perfringens is structurally related to the type IV secretion system protein VirB8 from Gram-negative bacteria, Molecular Microbiology [P], vol 83, issue 2, Wiley-Blackwell Publishing Ltd, UK, pp. 275-288.

Bantwal, R., Bannam, T.L., Porter, C.J., Quinsey, N.S., Lyras, D., Adams, V.M., Rood, J.I., 2012, The peptidoglycan hydrolase TcpG is required for efficient conjugative transfer of pCW3 in Clostridium perfringens, Plasmid [P], vol 67, issue 2, Academic Press, USA, pp. 139-147.

Carter, G.P., Rood, J.I., Lyras, D., 2012, The role of toxin A and toxin B in the virulence of clostridium difficile, Trends in Microbiology [P], vol 20, issue 1, Elsevier Ltd * Trends Journals, UK, pp. 21-29.

Walk, S., Jain, R., Trivedi, I., Grossman, S., Newton, D., Thelen, T., Hao, Y., Songer, J., Carter, G., Lyras, D., Young, V., Aronoff, D., 2011, Non-toxigenic Clostridium sordellii: Clinical and microbiological features of a case of cholangitis-associated bacteremia, Anaerobe [P], vol 17, issue 5, Elsevier Science Ltd, UK, pp. 252-256.

Richards, M., Knox, J., Elliott, B., Mackin, K., Lyras, D., Lynette, J., Riley, T., 2011, Severe infection with Clostridium difficile PCR ribotype 027 acquired in Melbourne, Australia, Medical Journal Of Australia [P], vol 194, issue 7, Australasian Medical Publishing Company Pty Ltd, Australia, pp. 369-371.

Carter, G.P., Awad, M.M., Kelly, M.L., Rood, J.I., Lyras, D., 2011, TcdB or not TcdB: a tale of two Clostridium difficile toxins, Future Microbiology [P], vol 6, issue 2, Future Medicine Ltd, UK, pp. 121-123.

Carter, G.P., Awad, M.M., Hao, Y., Thelen, T., Bergin, I.L., Howarth, P.M., Seemann, T., Rood, J.I., Aronoff, D.M., Lyras, D., 2011, TcsL Is an Essential Virulence Factor in Clostridium sordellii ATCC 9714, Infection And Immunity [P], vol 79, issue 3, American Society for Microbiology, USA, pp. 1025-1032.

Carter, G.P., Douce, G.R., Govind, R., Howarth, P.M., Mackin, K.E., Spencer, J., Buckley, A.M., Antunes, A., Kotsanas, D., Jenkin, G.A., Dupuy, B., Rood, J.I., Lyras, D., 2011, The anti-sigma factor TcdC modulates hypervirulence in an epidemic BI/NAP1/027 clinical isolate of Clostridium difficile, Plos Pathogens [P], vol 7, issue 10 (Art. No: e1002317), Public Library of Science, USA, pp. 1-11.

Chakravorty, A., Awad, M., Hiscox, T., Cheung, K., Carter, G., Choo, J., Lyras, D., Rood, J., 2011, The cysteine protease alpha-clostripain is not essential for the pathogenesis of Clostridium perfringens-mediated myonecrosis, PLoS ONE [P], vol 6, issue 7 (Art. No: e22762), Public Library of Science, USA, pp. 1-7.

Kotsanas, D., Carson, J., Awad, M.M., Lyras, D., Rood, J.I., Jenkin, G.A., Stuart, R., Korman, T., 2010, Novel use of tryptose sulfite cycloserine egg yolk agar for isolation of Clostridium perfringens during an outbreak of necrotizing enterocolitis in a neonatal unit, Journal Of Clinical Microbiology [P], vol 48, issue 11, American Society for Microbiology, USA, pp. 4263-4265.

Carter, G.P., Rood, J.I., Lyras, D., 2010, The role of toxin A and toxin B in Clostridium difficile-associated disease: Past and present perspectives, Gut Microbes [P], vol 1, issue 1, Landes Bioscience, USA, pp. 58-64.

Kennedy, C.L., Lyras, D., Cheung, K.J., Hiscox, T.J., Emmins, J.J., Rood, J.I., 2009, Cross-complementation of Clostridium perfringens PLC and Clostridium septicum alpha-toxin mutants reveals PLC is sufficient to mediate gas gangrene, Microbes and Infection, vol 11, issue 3, Elsevier Masson, France, pp. 413-418.

Kennedy, C.L., Lyras, D., Cordner, L.M., Melton-Witt, J., Emmins, J.J., Tweten, R.K., Rood, J.I., 2009, Pore-forming activity of alpha-toxin is essential for clostridium septicum-mediated myonecrosis, Infection and Immunity, vol 77, issue 3, American Society for Microbiology, USA, pp. 943-951.

Kennedy, C.L., Smith, D.J., Lyras, D., Chakravorty, A., Rood, J.I., 2009, Programmed cellular necrosis mediated by the pore-forming alpha-toxin from Clostridium septicum, Plos Pathogens [P], vol 5, issue 7 (e1000516), Public Library of Science, USA, pp. 1-11.

Chiarezza, M., Lyras, D., Pidot, S.J., Flores-Diaz, M., Awad, M.M., Kennedy, C.L., Cordner, L.M., Das, T.P., Poon, R., Hughes, M.L., Emmins, J.J., Alape-Giron, A., Rood, J.I., 2009, The NanI and NanJ sialidases of Clostridium perfringens are not essential for virulence, Infection And Immunity [P], vol 77, issue 10, American Society for Microbiology, USA, pp. 4421-4428.

Lyras, D., O'Connor, J.R., Howarth, P.M., Sambol, S.P., Carter, G.P., Phumoonna, T., Poon, R., Adams, V.M., Vedantam, G., Johnson, S., Gerding, D., Rood, J.I., 2009, Toxin B is essential for virulence of Clostridium difficile, Nature, vol 458, issue 7242, Nature Publishing Group, UK, pp. 1176-1179.

Lyras, D., Adams, V.M., Ballard, S.A., Teng, W.L., Howarth, P., Crellin, P., Bannam, T.L., Songer, J., Rood, J.I., 2009, tISCpe8, an IS1595-family lincomycin resistance element located on a conjugative plasmid in Clostridium perfringens, Journal Of Bacteriology [P], vol 191, issue 20, American Society for Microbiology, USA, pp. 6345-6351.

Tennant, S.M., Hartland, E.L., Phumoonna, T., Lyras, D., Rood, J.I., Robins-Browne, R.M., van Driel, I.R., 2008, Influence of gastric acid on susceptibility to infection with ingested bacterial pathogens, Infection and Immunity, vol 76, American Society of Microbiology, Washington, DC, USA, pp. 639-645.

Hickey, M.J., Kwan, R., Awad, M.M., Kennedy, C.L., Young, L.F., Hall, P.H., Cordner, L.M., Lyras, D., Emmins, J.J., Rood, J.I., 2008, Molecular and cellular basis of microvascular perfusion deficits induced by clostridium perfringens and clostridium septicum, P L o S Pathogens, vol 4, issue 4, Public Library of Science, United States, pp. 1-9.

Carter, G.P., Lyras, D., Allen, D.L., Mackin, K., Howarth, P., O'Connor, J.R., Rood, J.I., 2007, Binary toxin production in Clostridium difficile is regulated by CdtR, a LytTR family response regulator, Journal of Bacteriology, vol 189, issue 10, American Society of Microbiology, Washington, DC, USA, pp. 7290-7301.

O'Connor, J.R., Lyras, D., Farrow, K.A., Adams, V.M., Powell, D.R., Hinds, J., Cheung, K.J., Rood, J.I., 2006, Construction and analysis of chromosomal Clostridium difficile mutants, Molecular Microbiology, vol 61, issue 5, Blackwell Publishing, UK, pp. 1335-1351.

Bannam, T.L., Teng, W.L., Bulach, D.M., Lyras, D., Rood, J.I., 2006, Functional identification of conjugation and replication regions of the tetracycline resistance plasmid pCW3 from Clostridium perfringens, Journal of Bacteriology, vol 188, issue 13, Amer Soc Microbiology, WASHINGTON DC USA, pp. 4942-4951.

Adams, V.M., Lucet, I., Tynan, F.E., Chiarezza, M., Howarth, P., Kim, J., Rossjohn, J., Lyras, D., Rood, J.I., 2006, Two distinct regions of the large serine recombinase TnpX are required for DNA binding and biological function, Molecular Microbiology, vol 60, issue 3, Blackwell Publishing, UK, pp. 591-601.

Lucet, I.S., Tynan, F.E., Adams, V.M., Rossjohn, J., Lyras, D., Rood, J.I., 2005, Identification of the structural and functional domains of the large serine recombinase TnpX from Clostridium perfringens, The Journal of Biological Chemistry, vol 280, issue 4, American Society for Biochemistry and Molecular Biology, Inc., Bethesda USA, pp. 2503-2511.

Kennedy, C.L., Krejany, E.O., Young, L.F., O'Connor, J.R., Awad, M.M., Boyd, R.L., Emmins, J.J., Lyras, D., Rood, J.I., 2005, The alpha-toxin of Clostridium septicum is essential for virulence, Molecular Microbilology, vol 57, issue 5, Blackwell Publishing Ltd, UK, pp. 1357-1366.

Adams, V.M., Lucet, I.S., Lyras, D., Rood, J.I., 2004, DNA binding properties of TnpX indicate that different synapses are formed in the excision and integration of the Tn4451 family, Molecular Microbiology, vol 53, issue 4, Blackwell Publishing Ltd, Oxford UK, pp. 1195-1207.

Lyras, D., Adams, V.M., Lucet, I., Rood, J.I., 2004, The large resolvase TnpX is the only transposon-encoded protein required for transposition of the Tn4451/3 family of integrative mobilizable elements, Molecular Microbiology, vol 51, issue 6, Blackwell Publishing Ltd, Oxford UK, pp. 1787-1800.

Shultz, T.R., Tapsall, J.W., White, P.A., Ryan, C.S., Lyras, D., Rood, J.I., Binotto, E.W., Richardson, C.J.L., 2003, Chloramphenicol-resistant Neisseria meningitidis containing catP isolated in Australia, Journal of Antimicrobial Chemotherapy, vol 1, Oxford University Press, Oxford UK, pp. 856-859.

Mani, N., Lyras, D., Barosso, L., Howarth, P., Wilkins, T., Sonenshein, A.L., Rood, J.I., Dupuy, B., 2002, Environmental Response and Autoregulation of Clostridium difficile TXeR, a Sigma Factor for Toxin Gene Expression, Journal of Bacteriology, vol 184, issue 21, American Society for Microbiology, Washington DC, pp. 5971-5978.

Farrow, K.A., Lyras, D., Polekhina, G., Koutsis, K., Parker, M.W., Rood, J.I., 2002, Identification of Essential Residues in the Erm(B) rRNA Methyltransferase of Clostridium perfringens, Antimicrobial Agents and Chemotherapy, vol 46, issue 5, American Society for Microbiology, Washington DC USA, pp. 1253-1261.

Adams, V., Lyras, D., Farrow, K.A., Rood, J.I., 2002, The clostridial mobilisable transposons, Cellular and Molecular Life Sciences, vol 59, issue 12, Birkhauser Verlag Ag, Basel Switzerland, pp. 2033-2043.

Roberts, A.P., Johanesen, P.A., Lyras, D., Mullany, P., Rood, J.I., 2001, Comparison of Tn5397 from Clostridium difficile, Tn916 from Enterococcus faecalis and the CW459tet(M) element from Clostridium perfringens shows that they have similar conjugation regions but different insertion and excision modules, Microbiology, vol 147, issue 5, Society for General Microbiology, UK, pp. 1243-1251.

Farrow, K.A., Lyras, D., Rood, J.I., 2001, Genomic analysis of the erythromycin resistance element Tn5398 from Clostridium difficile, Microbiology, vol 147, Society for General Microbiology, UK, pp. 2717-2728.

Johanesen, P.A., Lyras, D., Rood, J.I., 2001, Induction of pCW3-encoded tetracycline resistance in clostridium perfringens involves a host-encoded factor, Plasmid, vol 46, issue 3, Academic Press, San Diego USA, pp. 229-232.

Johanesen, P.A., Lyras, D., Bannam, T.L., Rood, J.I., 2001, Transcriptional analysis of the tet(P) operon from Clostridium perfringens, Journal of Bacteriology, vol 183, issue 24, American Society of Microbiology, Washington DC USA, pp. 7110-7119.

Wang, H., Roberts, A.P., Lyras, D., Rood, J.I., Wilks, M., Mullany, P., 2000, Characterization of the ends and target sites of the novel conjugative transposon Tn5397 from Clostridium difficile: Excision and circulation is mediated by the large resolvase, TndX, Journal of Bacteriology, vol 182 issue 13, American Society for Microbiology, Washington USA, pp. 3775-3783.

Farrow, K.A., Lyras, D., Rood, J.I., 2000, The macrolide-lincosamide-strepogramin B resistance determinant from Clostridium difficile 630 contains two erm(B) genes, Antimicrobial Agents and Chemotherapy, vol 44 issue 2, Amercian Society for Microbiology, Washington USA, pp. 411-413.

Lyras, D., Rood, J.I., 2000, Transposition of Tn4451 and Tn4453 involves a circular intermediate that forms a promoter for the large resolvase, TnpX, Molecualar Microbiology, vol 38 issue 3, Blackwell Science Ltd, Oxford UK, pp. 588-601.

Johnson, S., Samore, M.H., Farrow, K.A., Killgore, G.E., Tenover, F.C., Lyras, D., Rood, J.I., De Girolami, P., Baltch, A.L., Rafferty, M.E., Pear, S.M., Gerding, D.N., 1999, Epidemics of diarrhea caused by a clindamycin-resistant strain of "Clostridium difficile" in four hospitals, The New England Journal of Medicine, vol 341 issue 22, Massachusetts Medical Society, Waltham USA, pp. 1645-1651.

Lyras, D., Storie, C., Huggins, A.S., Crellin, P.K., Bannam, T.L., Rood, J.I., 1998, Chloramphenicol resistance in Clostridium difficile is encoded on Tn4453 transposons that are closely related to Tn4451 from Clostridium perfringens, Antimicrobial Agents and Chemotherapy, vol 42 no 7, American Society for Microbiology, Washington USA, pp. 1563-1567.

Lyras, D., Rood, J.I., 1998, Conjugative transfer of RP4-oriT shuttle vectors from Escherichia coli to Clostridium perfringens, Plasmid, vol 39, Academic Press, Orlando USA, pp. 160-164.

Conference Proceedings

Rood, J.I., Lyras, D., Crellin, P.K., 1998, Mobilisable transposons from the clostridia, Microbiology Australia, Hobart 27 September - 2 October 1998, Ink Press International, Subiaco WA Australia, p. S50.3.

Farrow, K.A., Lyras, D., Rood, J.I., 1998, The erm determinant from Clostridium difficile strain 630 contains two ermBZ genes, Microbiology Australia, Hobart 27 September - 2 October 1998, Ink Press International, Subiaco WA Australia, p. P17.2.

Lyras, D., Melville, S.B., Rood, J.I., 1997, Conjugative transfer of shuttle and suicide vectors from Escherichia coli to Clostridium perfringens, Clostridia 97 - Pathogenesis, Onzain, France, 22-25/06/97, Societe Francaise de Microbiologie, Paris France, p. 73.

Lyras, D., Crellin, P.K., Rood, J.I., 1997, Functional analysis of chloramphenicol resistance transposons from Clostridium perfringens and Clostridium difficile, Clostridia 97 - Pathogenesis, 41150 Onzain, France, 22-25/06/97, Societe Francaise de Microbiologie, Paris, p. 27.

Rood, J.I., Crellin, P.K., Lyras, D., 1997, Site-specific excision and mobilisation of clostridial chloramphenicol resistance transposons, Transposition and site-specific recombination, Santa Fe, New Mexico, 01-07/03/97, Keystone Symposia, Silverthorne CO, p. 36.

Other

Johnson, E.A., Bradshaw, M., Rood, J.I., Lyras, D., 1999, Expression system for Clostridium species, USA.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Analysis of Clostridium difficile Colonisation Factors.
Supervisors:
Carter, G (Joint), Lyras, D (Joint-co).
Program of Study:
(MASTER'S BY RESEARCH).
Thesis Title:
Identification and characterisation of large plasmids in Clostridium difficile.
Supervisors:
Johanesen, P (Joint), Lyras, D (Joint-co).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Microbial biotransformation of 1,8-cineole and 1,8-cineole derivatives.
Supervisors:
Lyras, D (Joint-co), Dumsday, G (Associate), Johanesen, P (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Regulation of binary toxin production in Clostridium difficile.
Supervisors:
Rood, J (Joint-co), Cheung, K (Joint), Lyras, D (Joint).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Structural and proteomic characterisation of Clostridium sordellii spores.
Supervisors:
Awad, M (Joint), Lyras, D (Joint-co).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
The use of recombinant B. subtilis spores as C. difficile vaccines.
Supervisors:
Lyras, D (Main), Carter, G (Associate), Johanesen, P (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Understanding the role of the gut mucus layer in susceptibility to Clostridium difficile infection.
Supervisors:
Carter, G (Joint), Lyras, D (Joint-co).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Virulence Factors in Clostridium perfringens.
Supervisors:
Lyras, D (Main), Johanesen, P (Associate), Moore, R (Associate).

Completed Supervision

Student:
Adams, V.
Program of Study:
FUNCTIONAL ANALYSIS OF THE CLOSTRIDIAL LARGE RESOLVASE TNPX. (PHD) 2003.
Supervisors:
Rood, J (Main), Lyras, D (Associate).
Student:
Chakravorty, A.
Program of Study:
Understanding the host innate immune response to the histotoxic clostridia. (PHD) 2012.
Supervisors:
Rood, J (Main), Awad, M (Associate), Lyras, D (Associate).
Student:
Chiarezza, M.
Program of Study:
Analysis of the sialidases from Clostridium perfringens and Clostridium septicum. (PHD) 2007.
Supervisors:
Rood, J (Main), Lyras, D (Associate).
Student:
Farrow, K.
Program of Study:
ANALYSIS OF CLOSTRIDIAL MLS RESISTANCE DETERMINANTS. (PHD) 2001.
Supervisors:
Rood, J (Main), Lyras, D (Associate).
Student:
Kennedy, C.
Program of Study:
The role in virulence of the alpha-toxin Clostridium septicum. (PHD) 2008.
Supervisors:
Rood, J (Main), Lyras, D (Associate).
Student:
O'Connor, J.
Program of Study:
Construction and analysis of Clostridium difficile response regulator mutants. (PHD) 2007.
Supervisors:
Rood, J (Main), Farrow, K (Associate), Lyras, D (Associate).