National University of Ireland, Maynooth

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Faculties & Departments

Department of Biology

Dr. Kevin Kavanagh
Head of Laboratory

Medical Mycology Unit

Research Interests

 

KevinFungal pathogens are recognised as a significant cause of illness and death among patients immuno-compromised as a result of disease (AIDS, cancer) or therapy (immuno-suppressive therapy prior to organ transplantation). Most fungal pathogens are normal components of the body flora but in the event of an underlying disease they can become invasive and colonise many organs with deleterious consequences.

 

 The main aims of the work in the in the Medical Mycology Unit are:

  • understanding the mechanisms employed by fungi to colonise human tissue,
  • characterizing the role of the innate immune response in combating fungal infection and
  • developing therapies to complement existing anti-fungal strategies.

Aspergillus fumigatus is a filamentous fungus which is associated with a range of pulmonary diseases, a number of which can disseminate to distant sites in the body and have a mortality rate of over 95%. One project in the lab is concerned with evaluating the virulence of environmental isolates of this fungus and assessing the role of toxins in its ability to suppress the host’s immune response. Together with Dr. Sean Doyle (Department of Biology) we are developing novel diagnostics which will detect the presence of fungal toxins and enzymes in human blood as an early indicator of fungal infection. Our objective is to make earlier detection of fungal infection feasible so that anti-fungal therapy can be initiated with a consequent reduction in patient mortality.

 Conventional anti-fungal therapy relies upon the use of a range of azole and polyene drugs. While these are effective in the majority of cases, many have reduced efficacy due a range of adverse side effects and to the advent of drug resistance among pathogenic fungi. Together with Dr. Malachy McCann (Department of Chemistry) we are assessing the efficacy of novel metal-based anti-fungal drugs with a view to their possible use in treating a range of superficial fungal infections. To date we have identified the mode of action of these drugs and established their potential for controlling the growth of fungi by acting synergistically with conventional anti-fungal drugs. In collaboration with Drs. Denise Egan and Bernie Creaven (ITTallaght) we have identified a group of metal-coumarin complexes that show strong antifungal and antibacterial activity and which may have a potential role in the treatment of microbial infections of the skin.

 Recent work has focused on studying the response of insects to fungal infection. The insect immune system bears a high degree of similarity to the component of the human immune system, the innate response, which deals with fungal pathogens and can give an insight into how our bodies respond to attack by fungi. We have previously demonstrated that insects may be used in place of mammals for the testing of microbial pathogens and for assessing the efficacy of novel antimicrobial drugs.   Recent work has examined the similarities between the insect and mammalian responses to infection and examined structural and functional similarities between immune cells in insects called haemocytes and human neutrophils. By demonstrating the similarities between the immune system of insects and mammals we hope to strengthen the attractiveness of using insects in place of mammals for most routine in vivo pathogen testing thus reducing the need to use mammals for this type of work.

Funding Sources

Departmental, Environmental Protection Agency, European Union, Health Research Board, Higher Education Authority (PRTLI III and IV), Enterprise Ireland, National Rosacea Society (USA), Science Foundation Ireland, HETAC-Technology Sector Research Programme, Teagasc, Industrial.

Postdoctoral Fellow

  • Dr. Judy Kelly (October 2009)

Post-Graduate Students

  • Nessa Banville (October 2008-)
  • Niamh O'Reilly (October 2008-)
  • Alanna Smith (October 2008-)
  • Matthew O'Brien (October 2009-)
  • Ahmed Eshwika (October 2010 - )
  • Niall Browne (October 2011 - )

Peer Reviewed Publications 2002 - December 2010

 

1. RESEARCH PAPERS 

  • Ellabib M, Agaj M,  Khalifa Z and Kavanagh K (2002) Trichophyton violaceum as  an important cause of tinea capitis in children in Tripoli (Libya): Results of a two year survey. Mycopathologia  153: 145-147.
  • Daly, P. &  Kavanagh, K. (2002)  Immobilisation of Aspergillus fumigatus colonies in a soft agar matrix allows visualisation of A549 cell detachment and death. Medical Mycology  40: 27-33.
  • Ellabib MS, Khalifa Z &  Kavanagh K. (2002) Dermatophytes and other fungi associated with skin mycoses in Tripoli, Libya. Mycoses 45: 101-104.
  •  Ellabib M, Agaj M, Khalifa Z and Kavanagh K. (2002). Yeasts of the genus Candida are the dominant cause of onychomycosis in Libyan women but not men: Results of a two year surveillance study. British Journal of Dermatology 146: 1038-1041.
  • Brennan M, Thomas DY, Whiteway M and  Kavanagh K. (2002) Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae. FEMS Immunology and Medical Microbiology  34 (2): 153-157.
  • Coyle B., Kavanagh K., McCann M., Devereux M. and Geraghty M. (2003) Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes. Biometals 16: 321-329.
  • Deegan, O., Walshe, K. Kavanagh, K. and Doyle, S. (2003) Quantitative detection of C-reactive protein using phosphocholine-labelled enzymes or microspheres. Analytical Biochemistry 312: 175-181.
  • Geraghty, P. and Kavanagh, K. (2003) Erythromycin, an inhibitor of mitoribosomal protein biosynthesis, alters the Amphotericin B susceptibility of Candida albicans. Journal of Pharmacy and Pharmacology 55: 179-184.
  • Geraghty, P. and Kavanagh, K. (2003) Disruption of mitochondrial function in Candida albicans  leads to reduced cellular ergosterol levels and elevated growth in the presence of Amphotericin B.  Archives of Microbiology 179: 295-300.
  • McCann M, Coyle, B, Briody, J. Bass,  F. O'Gorman, N. Devereux, M., Kavanagh, K.,  McKee, V. (2003). Synthesis and anti-microbial activity of (Z)-3-(1H-imidazol-1-yl)-2-phenylpropenenitrile and its metal complexes: X-ray crystal structures of the Zn(II) and Ag(I) complexes. Polyhedron  22, 1595-1601.
  • Ellabib MS., Refaai, A. Khalifa, Z.  and Kavanagh K. (2003) Isolation and identification of Madurella mycetomatis from two cases of Black grain Mycetoma in Libya. Mycoses  46, 339-341.
  • O'Keeffe, J.,   Doyle, S.   and  Kavanagh, K. (2003).  Exposure of the yeast Candida albicans to the anti-neoplastic agent Adriamycin increases  the tolerance to Amphotericin B. Journal of Pharmacy and Pharmacology 55: 1629-1633.
  • Bergin, D., Brennan, M., and Kavanagh, K. (2003). Fluctuations in haemocyte density and microbial load may be used as  indicators of fungal pathogenicity in larvae of  Galleria mellonella. Microbes and Infection  5(15):  1389-1395.
  • Coyle, B, Kinsella, P, McCann, M, Devereux, M, O'Connor, R, Clynes M. and Kavanagh, K. (2004). Induction of apoptosis in yeast and mammalian cells by  exposure to 1,10 phenanthroline metal  complexes. Toxicology in Vitro 18(1): 63-70.
  • Fox, M., Gray, G., Kavanagh, K., Lewis, C.  and Doyle, S.  (2004). Detection of Aspergillus fumigatus mycotoxins: immunogen synthesis and immunoassay development. Journal of Microbiological Methods  56: 221-230.
  • Kavanagh, K.  and Reeves, E.P. (2004) Exploiting the potential of Insects for in vivo pathogenicity testing of Microbial pathogens. FEMS Microbiology Reviews. 28: 101-112.
  • O’Keeffe, J. and Kavanagh, K. (2004)  Adriamycin alters the expression of drug efflux pumps and confers Amphotericin B tolerance in Candida albicans.  Anticancer Research 24: 405-408.
  • Kavanagh, K. and Dowd, S. (2004). Histatins: Anti-fungals with a promising future. Journal of Pharmacy and Pharmacology 56: 285-289.
  • Abuskhuna, A., Briody, J., McCann, M., Devereux, M., Kavanagh, K., Fontecha, J.B., McKee, V. (2004). Synthesis, structure and anti-fungal activity of dimeric Ag(1) complexes containing bis-imidazole ligands. Polyhedron  23;  1249 - 1255.
  • Eshwika, A., Coyle, B, Devereux, M,  McCann, M. and  Kavanagh, K. (2004).  Metal-complexes of 1, 10 phenanthroline-5,6-dione alter the susceptibility of the yeast  Candida albicans to Amphotericin B and Miconazole. Biometals 17: 415 - 422.
  • Reeves, E.P., Murphy, T., Daly, P.   and Kavanagh, K. (2004). Amphotericin B enhances the synthesis and release of the immunosuppressive agent gliotoxin from the pulmonary pathogen Aspergillus fumigatus. Journal of Medical Microbiology 53, 719-725.
  • Coyle, B, McCann, M, Kavanagh, K. Devereux,M., McKee, V. Kayal, N. Egan, D. Deegan, C.. Finn, G. (2004). Synthesis, X-ray Crystal Structure, Anti-Fungal and Anti-Cancer Activity of [Ag2(NH3)2(salH)2] (salH2 = Salicylic Acid). Journal of Inorganic Biochemistry  98, 1361 – 1366.
  • Reeves, EP., .Messina, CGM, Doyle, S. and Kavanagh, K. (2004) Correlation of Gliotoxin Production and Virulence of Aspergillus fumigatus in Galleria mellonella. Mycopathologia 158, 73-79.
  • Devereux, M., McCann, M., O Shea, D., Kelly , R., Egan,D.,  C. Deegan C., Kavanagh, K. and McKee, V.  (2004) Synthesis, antimicrobial activity and chemotherapeutic potential of inorganic derivatives of 2-(4’-thiazolyl)benzimazole {thiabendazole}: X-ray crystal structures of [Cu(TBZH)2Cl]Cl.H2O.EtOH and TBZH2NO3 (TBZH = thiabendazole), Journal of Inorganic Biochemistry 98, 1023-1031.
  • McCann, M, Coyle, B, McKay, S, McCormack, P, Devereux, M, Kavanagh, K, McKee, V, Kinsella, P, O'Connor, R, Clynes, M. (2004).   Synthesis and X-ray Crystal Structure of [Ag(phendio)2]ClO4 (phendio = 1,10-Phenanthroline-5,6-dione) and its Effects on Fungal and Mammalian Cells. Biometals 17; 635-645.
  • Neville, C., Murphy, A., Kavanagh, K.  and Doyle S. (2005) A 4’-phosphopantetheinyl transferase mediates non-ribosomal peptide synthetase activation in Aspergillus fumigatus. ChemBiochem 6(4):679-685.
  • Burns C, Geraghty R, Neville C, Murphy A, Kavanagh K, Doyle S. (2005). Identification, cloning, and functional expression of three glutathione transferase genes from Aspergillus fumigatus. Fungal Genet Biol. 42:319-27.
  • Creaven,BS. Egan, DA.  Kavanagh, K McCann, M Mahon,M Noble,A Thati,B Walsh. M (2005). Synthesis and Antimicrobial Activity of Copper(II) and Silver(I) Complexes of Hydoxynitrocoumarins:  X-ray crystal structures of [Cu(hnc)2(H2O)2]×2H2O and [Ag(hnc)] (hncH = 4-hydroxy-3-nitro-2H-chromen-2-one) Polyhedron 24, 949-957.
  • Bergin, D. Reeves, EP, Renwick, J. Wientjes FB.  and Kavanagh, K. (2005).  Superoxide production in haemocytes of Galleria mellonella – identification of proteins homologous to the NADPH oxidase complex of human neutrophils. Infection and Immunity 73, 4161-4173.
  • Reiber K., Reeves, E.P, Neville C.M., Winkler, R., Gebhardt, P.,  Kavanagh, K. and Doyle S. (2005). The expression of selected non-ribosomal peptide synthetases in Aspergillus fumigatus is controlled by the availability of free iron. FEMS Microbiology Letters  248, 83-91.
  • Rowan, R, Tallon, T Sheahan, A., Curran, R., McCann, M., Kavanagh, K. Devereux, M. and McKee V.  (2006)  ‘Silver bullets’ in antimicrobial chemotherapy: synthesis, characterisation and biological screening of some new Ag(I)-containing imidazole complexes. Polyhedron 25, 1771-1778.
  • Carberry, S., Neville, C., Kavanagh, K. and Doyle, S. (2006). Analysis of major intracellular proteins of Aspergillus fumigatus by MALDI mass spectrometry: Identification and characterisation of an elongation factor 1B protein with glutathione transferase activity. Biochemical and Biophysical Research Communications 341: 1096-1104.
  • Renwick, J.  Daly, P., E. Reeves and  Kavanagh, K. (2006) “Susceptibility of larvae of Galleria mellonella to infection by Aspergillus fumigatus is dependent upon stage of conidial germination”. Mycopathologia 161, 377-384.
  • Reeves EP., Nagl, M., O’Keeffe, J.,Kelly, J.,  and Kavanagh, K.(2006).  The effect of N-chlorotaurine on Aspergillus, with particular reference to the destruction of secreted gliotoxin. Journal of Medical Microbiology 55; 913-918.
  • Bergin, D.  Murphy,L  Keenan,J  Clynes M and Kavanagh,K. (2006).  Pre-exposure to yeast protects larvae of Galleria mellonella from a subsequent lethal infection by  Candida albicans and is mediated by the increased expression of antimicrobial peptides. Microbes and Infection.8, 2105-2112.
  • Creaven BS,  Egan DA,  Kavanagh, K., McCann,, M., Noble, A Thati,  B., Walsh. M. (2006) Synthesis, anti-microbial and anti-cancer activity of a series of substituted coumarin-3-carboxylatosilver(I) complexes. Inorganica Chimica Acta 359, 3976-3984.
  • Reeves, E.P., Reiber, K., Neville, C., Scheibner, O., Kavanagh, K. & Doyle S. (2006). A nonribosomal peptide synthetase (pes1) confers protection against oxidative stress in Aspergillus fumigatus. FEBS J 273, 3038-3053.
  • Renwick, J., Reeves, E.P., Frans B. Wientjes,  Kavanagh, K. (2007) Translocation of proteins homologous to human neutrophil p47phox and p67phox to the cell membrane in activated hemocytes of Galleria mellonella. Developmental and Comparative Immunology 31: 347-359.
  • Thatti, B, Noble A., Creaven BS., Walsh M., McCann M.,Kavanagh, K. Devereux, M and Egan, D. (2007). In vitro anti-tumour and cyto-selective effects of coumarin-3-carboxylic acid and three of its hydroxylated derivatives, along with their silver-based complexes, using human epithelial carcinoma cell lines" Cancer Letters 248: 321-331.
  • Thati, B., Noble, A., Creaven, B., Kavanagh, K., McCann, M., Devereux, M. Egan, D. (2007) A study of the role of apoptotic cell death and cell cycle events mediating the mechanism of action of 6-hydroxycoumarin-3-carboxylatosilver in human malignant hepatic cells. Cancer Let. 250: 128-139.
  • Vickers, I., Reeves, E.P., Kavanagh, K. and Doyle, S. (2007). Isolation, activity and immunological characterisation of a secreted aspartic protease, CtsD, from Aspergillus fumigatus. Protein Expression and Purification 53: 216-224.
  • Lacey, N., Delaney, S., Kavanagh, K. and Powell, FC (2007) Mite related antigens stimulate inflammatory cells in rosacea. British Journal of Dermatology 157: 474-481.
  • Creaven,B., Egan D. Karcz, D., Kavanagh,K ., McCann, M., Mahon,  M. Noble, A..,  Thati,a B., Walsh. M. (2007) . Synthesis, characterisation, antimicrobial and in vitro anticancer activity of copper(II) and manganese(II) complexes of 2-(2-oxo-2H-chromen-6yloxy-7carboxymethyloxy)acetic acid (coumarin-6,7-dioxyacteic acid, cdoaH2) and 2-(2-oxo-2H-chromen-4-methyl-6yloxy-7carboxymethyloxy)acetic acid, (4-methylcoumarin-6,7-dioxyacteic acid, 4-MecdoaH2): X-ray Crystal structures of the phenanthroline adducts [Cu(cdoa)(phen)2]·8.8H2O and [Cu(4-mecdoa)(phen)2]·13H2O Journal of Inorganic Biochemistry 101, 1108-1119.
  • Thati B, Noble A.,  Rowan R.,  Creaven BS, Walsh M, McCann M, Egan D.,  Kavanagh K. (2007). Mechanism of action of coumarin and silver(I)-coumarin complexes against the pathogenic yeast Candida albicans. Toxicology in Vitro 21, 801-808.
  • B Thati, A Noble, B  Creaven, MWalsh, KKavanagh, D Egan (2007). An in vitro investigation of the induction of  apoptosis and modulation of cell cycle events in human cancer cells  by bisphenanthroline-coumarin-6,7-dioxacetatocopper(II) complex Chemico-Biological Interactions. 168, 143-158.
  • S. Abuskhuna, M. McCann, J. Briody, M. Devereux, K. Kavanagh, N. Kayal, V. McKee (2007).  Synthesis and structure of metal complexes containing zwitterionic N-hydroxyimidazole ligands. Polyhedron, 24, 949-957.
  • R. Curran, J. Lenehan, M. McCann, K. Kavanagh, M. Devereux, D.A. Egan, G. Clifford, K. Keane, B.S. Creaven, V. McKee, [Ag2(aca)2]n and [Ag4(aca)4(NH3)2] (acaH = 9-anthracenecarboxylic acid): synthesis, X-ray crystal structures, antimicrobial and anti-cancer activites. Inorg. Chem. Commun. 2007. (in press).
  • Mowlds, P and Kavanagh, K. (2008). Effect of pre-incubation temperature on susceptibility of Galleria mellonella to infection by Candida albicans. Mycopathologia 165 5-12.
  • Mowlds, P.,   Barron, A.  and Kavanagh, K. (2008). Physical stress primes the immune response of Galleria mellonella larvae to infection by Candida albicans.   Microbes and Infection  10, 628-634.
  • Kelly J., Rowan R, McCann M and Kavanagh K. (2008)  Exposure to Caspofungin activates Cap and Hog pathways in Candida albicans. Medical Mycology (in press).
  • B. Thatti, A. Noble, B. Creaven, M. Walsh, M. McCann, M. Devereux, K. Kavanagh and  D. Egan (2009). Role of cell cycle events and apoptosis in mediating the anti-cancer activity of a silver(I) complex of 4-hyoxy-3-nitro-coumarin-bis(phenanthroline) in human malignant cancer cells Eur J Pharmacology. 602, 203-214.
  • Rowan R,  Moran C,  McCann M and Kavanagh K (2009). Use of Galleria mellonella larvae to evaluate the in vivo anti-fungal activity of  [Ag2(mal)(phen)3] Biometals 22, (3) 461-467. (DOI: 10.1007/s10534-008-9182-3).
  • Rowan R, McCann M and Kavanagh K. (2010) Analysis of the response of Candida albicans cells to Silver (I) Medical Mycology 48, 498-505. 
  • Li, J., O'Reilly, N., Sheha, H.,   Katz, R.,   Raju, V.K., Kavanagh,  K.,  Tseng, SC. (2010).  Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Microbial Proteins in Patients with Facial Rosacea. Opthamology 117, 870-877. 
  • Kelly, J. and Kavanagh, K. (2010). Proteomic analysis of proteins released from growth-arrested Candida albicans following exposure to caspofungin. Medical Mycology. 48, 598-605. 
  • Mowlds P.,  Coates C., Renwick  J. and Kavanagh K. (2010). Dose-dependent cellular and humoral responses in Galleria mellonella larvae following beta-Glucan inoculation. Microbes and Infection 12; 146-153.  (Faculty of 1000 recommended article). 
  • Kavanagh, K. and Fallon, J.(2010).  Galleria mellonella larvae as models for studying fungal virulence. Fungal Biology Reviews 24, 79-83. 
  • Schrettl, M, Carberry, S, Kavanagh, K, Haas, H, Jones GW, O‚Brien J, Stephens J, Fenelon O, Nolan A and Doyle, S. (2010)  Self-Protection against Gliotoxin- A Component of the Gliotoxin Biosynthetic Cluster, GliT, Completely Protects Aspergillus fumigatus Against Exogenous Gliotoxin. PLOS Pathogens. June 2010 Issue 6. 
  • Fallon, J., Reeves, E. and Kavanagh, K. (2010) Inhibition of neutrophil function following exposure to the Aspergillus fumigatus toxin, fumagillin. Journal of Medical Microbiology 59, 625-633. 
  • Kelly  J.  and  Kavanagh K. (2010). Caspofungin primes the immune response of larvae of Galleria mellonella and induces a non-specific antimicrobial response. Journal of Medical Microbiology (in press). 
  • Fisher JF,  Kavanagh K, Sobel JD,  Kauffman CA , Newman CA. (2011).  Candida Urinary Tract Infections—Pathogenesis. Clinical Infectious Diseases (in press).

  • Davis, C., Carberry S., Schrettl, M., Singh I.,  Stephens, J., Barry, S., Kavanagh, K., Challis, Broughan D., Doyle, S. (2011). The Role of Glutathione S-transferase GliG in Gliotoxin Biosynthesis in Aspergillus fumigatus, CHEMISTRY-BIOLOGY (in press).

2. BOOK CHAPTERS  (Peer Reviewed)

  • Kavanagh, K. & Whittaker P.A. (2002) Protoplasts. In Encyclopedia of Molecular Biology. Publisher Wiley and Sons (New York).  (http://www.mrw.interscience.wiley.com/embm/.)
  • Kavanagh K., & Whittaker P. (2002) Protoplast Fusion. In Encyclopedia of Molecular Biology. Publisher Wiley and Sons (New York). (http://www.mrw.interscience.wiley.com/embm/.)
  • Kavanagh K & Sullivan D (2004). ‘Biology of Microorganisms: Fungi.’  Chapter 4 in Pharmaceutical Microbiology (pp 44-58). Editors: S. Denyer, N.A. Hodges & S. Gorman &. (seventh edition). Publishers: Blackwells. (ISBN: 0-632-06467-6). (This book sold 4821 copies within the first 6 months of publication)
  • Kavanagh, K. (2005)  Fungal Fermentation: Technology and Products.  Chapter 4 (p89 – 112)  in 'Fungi: Biology and Applications'. Editor: K. Kavanagh. Publishers: Wiley & Co. Ltd., Chichester, UK. (ISBN: 0470867027 paperback, 0470867019 hardback)
  • Geraghty, P & Kavanagh, K. (2006) Extraction and Detection of DNA and RNA from Yeast. Chapter 8 (pp159-179)  in Medical Mycology: Cellular and Molecular Techniques.  Publishers:. Wiley & Co. Ltd. Chichester, UK (ISBN: 0-470-01923-9 hardback) Edit: K. Kavanagh (Published: October  2006).
  • Renwick, J. and Kavanagh, K. (2007). Insects as models for studying the virulence of fungal pathogens of humans. Chapter 3 (pp45 – 67) in New Insights in Medical Mycology. Ed. K. Kavanagh, Publishers:  Springer. ISBN978-1-4020-6396-1 (published October 23, 2007).

3. COMMISSIONED BOOKS

  • Kavanagh K (2001). A Teachers Guide to Studying the Virulence factors of the Yeast Candida albicans.  Published by Society for General Microbiology., Reading, UK.
  • Kavanagh, K. (2005).  Editor  'Fungi: Biology and Applications'. Publishers: Wiley & Co. Ltd. Chichester, UK  (ISBN: 0470867027 paperback, 0470867019 hardback). (This book sold 844 copies (690 paper-back and 154 hardback) in the first year of publication), (1031 paper-back and 226 hardback copies sold within 2 years of publication).
  • Kavanagh, K. (2006) Editor of: Medical Mycology.: Cellular and Molecular Techniques.  Publishers:. Wiley & Co. Ltd. Chichester, UK (ISBN: 0-470-01923-9 hardback) (Published: October  2006). (This book sold 513 copies within the first year of publication).
  • Kavanagh, K. (2007) New Insights in Medical Mycology. Publishers:  Springer. ISBN978-1-4020-6396-1 (published October 23, 2007). (This book sold 86 copies within the first two months of publication).

 

Last edited: Tuesday, 15-Nov-2011 10:27:55 GMT

Biology Department , NUI Maynooth
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