| Contact Details |
E: Kevin.Saliba@anu.edu.au
T: (+61 2) 6125 7549
F: (+61 2) 6125 0313 |
| Main Research interests
|
|
Physiology and biochemistry of the malaria parasite.
|
| Teaching Activities |
Medical School
, Physiology and Pharmacology. Second Year Student Coordinator. |
| Current Research Group |
Adele Lehane – PhD Student
Christina Spry – PhD Student
Nimeka Ramanayke – PhD Student
Kylie Easton - Honours Student
Audrey Chan - Technical Officer
Kanchuka Gunaratna - Research Assistant
|
| Research Activities |
Each year the human malaria parasite Plasmodium falciparum
infects hundreds of millions of people and kills more than one million
children under the age of five, most of them in Africa. The stage of the
parasite that results in all the morbidity and mortality associated with
malaria, infects, resides within and ultimately destroys the red blood
cells of the human host.
Our work aims to identify and characterise physiological and biochemical
pathways in this stage of the parasite’s lifecycle which may be
utilised as targets for antimalarial chemotherapy. One such pathway that
is currently under investigation is the enzyme-mediated conversion of
the essential vitamin pantothenic acid (vitamin B5) into the
important enzyme cofactor coenzyme A. |
| Publications |
2009
Spry C and Saliba KJ (2009) The human malaria parasite Plasmodium falciparum is not dependent on host coenzyme A biosynthesis. Journal of Biological Chemistry, 284: 24904-24913
Kirk, K., Howitt, S.M., Bröer. S., Saliba, K.J. and Downie, M.J. (2009) Purine uptake in Plasmodium: transport versus metabolism. Trends in Parasitology, 25, 246-249 [PubMed]
2008
Saliba, K.J., Lehane, A.M. and Kirk K. (2008) A polymorphic drug pump in the malaria parasite. Molecular Microbiology, 70, 775-779. [PubMed]
D.A. van Schalkwyk, W. Priebe, K.J. Saliba (2008) The inhibitory effect of 2-halo derivatives of D-glucose on glycolysis and on the proliferation of the human malaria parasite Plasmodium falciparumJournal of Pharmacology and Experimental Therapeutics (accepted 18 August)
Adele M Lehane and Kevin J Saliba (2008) Common dietary flavonoids inhibit
the growth of the intraerythrocytic malaria parasite. BMC Research
Notes, 1:26 (accepted 18 June)
Lehane, A.M., Hayward, R., Saliba K.J. and Kirk, K. (2008) A verapamil-sensitive
chloroquine-associated H+ leak from the digestive vacuole of
chloroquine-resistant malaria parasites. Journal of Cell Science,
121, 1624-1632.[PubMed]
Downie, M.J., Saliba, K.J., Bröer, S., Howitt, S.M. and Kirk, K.
(2008) Purine nucleobase transport in the intraerythrocytic malaria parasite.
International Journal for Parasitology, 38:
203-209.
Spry, C., Kirk, K., Saliba, K.J. (2008) Coenzyme A biosynthesis: an antimicrobial
drug target. FEMS Microbiology Reviews, 32: 56-106
2007
Lehane, A.M., Marchetti, R.V., Spry, C., van Schalkwyk, D.A., Teng, R.,
Kirk, K. and Saliba K.J. (2007) Feedback inhibition of pantothenate kinase
regulates pantothenol uptake by the malaria parasite. Journal
of Biological Chemistry, 32: 25395-25405.
Staines, H.M., Alkhalil, A., Allen, R.J., De Jonge, H., Derbyshire, E.,
Egee, S., Ginsburg, H., Hill, D.A., Huber, S., Kirk, K., Lang, F., Lisk,
G., Oteng, E., Pillai, A.D., Rayavara, K., Rouhani, S., Saliba, K.J.,
Shen, C., Solomon, T., Thomas, S., Verloo, P., Desai, (2007) Electrophysiological
studies of malaria parasite-infected erythrocytes S.A. International
Journal for Parasitology, 37:475-482.
Kirk, K. and Saliba, K.J. (2007) Targeting nutrient uptake mechanisms
in Plasmodium. Current Drug Targets, 8:75-88.
2006
Saliba, K.J., Martin, R.E., Bröer, A., Henry, R.I., McCarthy, C.S.,
Downie, M.J., Allen, R.J.W., Mullin, K.A., McFadden, G.I., Bröer, S.and
Kirk, K. (2006) Sodium-dependent uptake of inorganic phosphate by
the intracellular malaria parasite. Nature 443:582-585
Downie, M.J., Saliba, K.J., Howitt, S.M., Bröer, S. and Kirk, K. (2006)
Transport of nucleosides across the Plasmodium falciparum parasite
plasma membrane has characteristics of PfENT1. Molecular Microbiology,
60:738-748.
Hayward, R., Saliba, K.J. and Kirk, K. (2006) The pH of the digestive vacuole
of Plasmodium falciparum is not associated with chloroquine resistance,
Journal of Cell Science, 119:1016-1025
2005
Spry, C., Chai, C.L.L., Kirk, K., Saliba, K.J. (2005) A class of pantothenic
acid analogs inhibits Plasmodium falciparum pantothenate kinase
and represses the proliferation of malaria parasites, Antimicrobial
Agents and Chemotheapy, 49:4649-4657.
Hayward, R., Saliba, K.J. and Kirk, K. (2005) pfmdr1 mutations
associated with chloroquine resistance incur a fitness cost in Plasmodium
falciparum. Molecular Microbiology, 55:1285-1295.
Hayward, R., Saliba, K.J. and Kirk, K. (2005) Mutations in pfmdr1
modulate the sensitivity of Plasmodium falciparum to the intrinsic
antiplasmodial activity of verapamil. Antimicrobial Agents and Chemotherapy,
49:840-842.
Kirk, K., Martin, R.E., Bröer, S., Howitt, S.M. and Saliba, K.J. (2005)
Plasmodium Permeomics: Membrane transport proteins in the malaria
parasite. Current Topics in Microbiology and Immunology: Malaria
(S. Krishna and D. Sullivan, eds), 295:325-356.
Saliba, K.J., Ferru, I. and Kirk, K. (2005) Pro-vitamin B5 (pantothenol)
inhibits the growth of the intraerythrocytic malaria parasite. Antimicrobial
Agents and Chemotherapy, 49:632-637.
Saliba, K.J. and Kirk, K. (2005) CJ-15,801, a fungal natural product, inhibits
the intraerythrocytic stage of Plasmodium falciparum in vitro via
an effect on pantothenic acid utilisation. Molecular and Biochemical
Parasitology, 141:129-131.
2004
Lehane, A.M., Saliba, K.J., Allen, R.J.W. and Kirk, K. (2004) Choline uptake
into the malaria parasite is energised by the membrane potential. Biochemical
and Biophysical Research Communications, 320:311-317.
Saliba, K.J., Krishna, S. and Kirk, K. (2004) Inhibition of hexose transport
and abrogation of pH homeostasis in the intraerythrocytic malaria parasite
by an O-3-hexose derivative. FEBS Letters, 570:93-96.
Go, M.-L., Liu, M., Wilairat, P., Rosenthal, P.J., Saliba, K.J. and Kirk,
K. (2004) Anti-plasmodial chalcones inhibit sorbitol-induced hemolysis of
Plasmodium falciparum-infected erythrocytes. Antimicrobial
Agents and Chemotherapy, 48:3241-3245.
2003
Saliba, K.J., Allen, R.J.W., Zissis, S., Bray, P.G., Ward, S.A. and Kirk,
K. (2003) Acidification of the malaria parasite's digestive vacuole by
a H+-ATPase and a H+-pyrophosphatase. Journal
of Biological Chemistry, 278:5605-5612.
Kirk, K. and Saliba, K.J. (2003) The membrane physiology of the 'malaria-infected'
erythrocyte, in Red Cell Membrane Transport in Health and Disease
(I. Bernhardt and J.C. Ellory, eds.) Springer, pp 569-585.
2002
Bray, P.G., Saliba, K.J., Davies, J.D., Spiller, D.G., White, M.R.H., Kirk,
K. and Ward, S.A. (2002) Distribution of acridine orange fluorescence in
Plasmodium falciparum-infected erythrocytes and its implications
for the evaluation of digestive vacuole pH. Molecular and Biochemical
Parasitology, 119:301-304.
Bray, P.G., Saliba, K.J., Davies, J.D., Spiller, D.G., White, M.R.H., Kirk,
K. and Ward, S.A. (2002) Further comments on the distribution of acridine
orange fluorescence in P. falciparum-infected erythrocytes. Molecular
and Biochemical Parasitology, 119:311-313.
2001
Elliott, J.L., Saliba, K.J. and Kirk, K. (2001) Transport of lactate and
pyruvate in the intraerythrocytic malaria parasite, Plasmodium falciparum.
Biochemical Journal, 355:733-739.
Saliba, K.J. and Kirk, K. (2001) H+-coupled pantothenate transport
in the intracellular malaria parasite. Journal of Biological Chemistry,
276:18115-18121.
Biagini, G. A., Knodler, L. A., Saliba, K.J., Kirk, K. and Edwards, M.
R. (2001) Na+-dependent pH regulation by the microaerophilic
parasite Giardia intestinalis. Journal of Biological Chemistry,
276:29157-29162.
Saliba, K.J. and Kirk, K. (2001) Nutrient acquisition by intracellular
apicomplexan parasites: Staying in for dinner. International Journal
of Parasitology, 31:1321-1330.
Kirk, K. and Saliba, K.J. (2001) Chloroquine resistance and the pH of the
malaria parasite's digestive vacuole. Drug Resistance Updates,
4:335-338.
2000
Reed, M.B., Saliba, K.J., Caruana, S.R., Kirk, K. and Cowman, A.F. (2000)
Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium
falciparum. Nature, 403:906-909.
Krishna, S.J., Woodrow, C., Burchmore, R., Saliba, K.J. and Kirk, K. (2000)
Hexose transport in asexual stages of Plasmodium falciparum and
Kinetoplastidae. Parasitology Today, 16:516-521.
1999
Rickards, R.W., Rothschild, J.M., Willis, A.C., de Chazal, N.M., Kirk,
J., Kirk, K., Saliba, K.J. and Smith, G.D. (1999) Calothrixins A and B,
novel pentacyclic metabolites from Calothrix cyanobacteria with potent activity
against malaria parasites and human cancer cells. Tetrahedron,
55:13513-13520.
Saliba, K.J. and Kirk, K. (1999) pH regulation in the intracellular malaria
parasite, Plasmodium falciparum: H+extrusion via a V-type
H+-ATPase. Journal of Biological Chemistry, 274:33213-33219.
Kirk, K., Staines, H.M., Martin, R.E. and Saliba, K.J. (1999) Transport
properties of the host cell membrane, in Transport and Trafficking in the
Malaria-Infected Erythrocyte , Wiley, Chichester (Novartis Foundation Symposium
226) pp 55-73.
Saliba, K.J., Martin, R.E., Staines, H.M. and Kirk, K. (1999) A novel anion
channel in the malaria-infected erythrocyte: opportunities for antimalarial
chemotherapy, in Chloride Channels (R.Z. Kozlowski, ed.) Isis Medical
Media, pp 137-148.
1998
Saliba, K.J., Folb, P.I. and Smith, P.J. (1998) Role for the Plasmodium
falciparum digestive vacuole in chloroquine resistance. Biochemical
Pharmacology, 56:313-320.
Saliba, K.J., Horner, H.A. and Kirk, K. (1998) Transport and metabolism
of the essential vitamin pantothenic acid in human erythrocytes infected
with the malaria parasite Plasmodium falciparum. Journal of
Biological Chemistry, 273:10190-10195.
Saliba, K.J. and Kirk, K. (1998) Uptake of an antiplasmodial protease inhibitor
into Plasmodium falciparum-infected human erythrocytes via a parasite-induced
pathway. Molecular and Biochemical Parasitology, 94:297-301.
Saliba, K.J. and Kirk, K. (1998) Clotrimazole inhibits the growth of Plasmodium
falciparum in vitro. Proceedings of the Royal Society of Tropical
Medicine and Hygiene, 92:666-667. |