School of Biological Sciences
Faculty of Sciences
Eligible to supervise Masters and PhD - email supervisor to discuss availability.
My laboratory studies the human specific bacterial pathogen Shigella flexneri which causes bacillary dysentery.
Current research areas are :
1) Role of membrane proteins in biosynthesis of LPS O antigen and Enterobacterial Common Antigen
2) Function of LPS O antigen in pathogenesis
3) Function of IcsA protein in pathogenesis
- My Research
- Grants and Funding
- Professional Activities
Invasive Bacterial Pathogens Laboratory
My laboratory conducts research into a number of enteric and invasive bacterial pathogens with a focus on the role of bacterial cell surface molecules in bacterial pathogenesis.
My research interests are:
PhD and Honours Projects
A number of challenging projects are available to interested PhD and Honours students. These projects will be in the general area of Shigella flexneri virulence factors, with an emphasis on the structure and function of IcsA, on lipopolysaccharide (LPS) O antigen biosynthesis proteins, and bacterial cell biology. Project information is available in the Honours and PhD page of the School website.
Other Pathogens we have Studied Include:
Salmonella enterica Typhi
Salmonella enterica Typhimurium
Vibrio cholerae O1
Shigella flexneri are Gram-negative bacteria that cause bacillary dysentery (shigellosis) in humans, and result in over 100 million episodes of diarrhea and 1000's of deaths each year.
Shigellosis arises due to poor sanitation and hygiene, and is transmitted by the oral-faecal route. Antibiotic therapy is frequently ineffective due to multi-antibiotic resistance. Shigellae are facultative intracellular pathogens able to invade, replicate within, and kill intestinal cells, and can also spread from cell to cell without going through an extracellular stage.
The infection results in an acute inflammatory response in the colon that causes the majority of the disease symptoms. S. flexneri bacteria are able to invade intestinal cells and replicate within them. After escaping into the cytosol, they replicate and exhibit intracellular motility in which the polarly localized cell surface protein IcsA recruits host proteins to generate actin-based motility (ABM). ABM allows the bacteria to spread from cell to cell thereby creating a focus of infection.
Lum, M., and Morona R. (2014) Dynamin-related protein Drp1 and mitochondria are important for Shigella flexneri infection. Int J Med Microbiol. 2014 Apr 3. pii: S1438-4221(14)00027-7. doi: 10.1016/j.ijmm.2014.03.006. [Epub ahead of print]
Lum, M., and Morona R. (2014) Myosin IIA is essential for Shigella flexneri cell-to-cell spread. Pathog Dis. doi: 10.1111/2049-632X.12202.
Lum, M., Attridge, S.R., and Morona R. (2013) Impact of dynasore an inhibitor of dynamin II on Shigella flexneri Infection. PLoS One. 8(12):e84975. doi: 10.1371/journal.pone.0084975. eCollection 2013.
Actin Based Motility
Actin based motility (ABM) is used by a number of microbial pathogens to move inside and between infected host (animal and human) cells. In Shigella flexneri, the outer membrane IcsA protein is reponsible for nucleating actin polymerisation by subverting host cell actin and actin regulatory proteins (e.g. N-WASP, Arp2/3 complex, Profilin, Cofilin, CapZ).
ABM can be visualized by staining using FITC-phalloidin to detect the F-actin comet tails that are formed. Additionally, time-lapse video microscopy can be used to visualise and measure the rate of motility.
In addition to IcsA, bacterial factors such as lipopolysaccharides also impact on IcsA function and intercellular spreading.
Morona, R., and Van Den Bosch, L. (2003) "Lipopolysaccharide O antigen chains mask IcsA(VirG) in Shigella flexneri" FEMS Microbiol. Lett. 221: 173-180.
Morona, R., and Van Den Bosch, L. (2003) "Multi-copy icsA is able to suppress the virulence defect caused by the wzzSF mutation in Shigella flexneri." FEMS Microbiol. Lett. 221: 213-219.
Van Den Bosch, L. and Morona, R. (2003) "The actin-based motility defect of Shigella flexneri rmlD rough LPS mutant is not due to loss of IcsA polarity." Microb. Pathogen. 35: 11-18.
Van Den Bosch, L., Manning, P.A., and Morona, R. (1997) “Regulation of O-antigen chain length is required for Shigella flexneri virulence”. Mol. Microbiol. 23: 765-775
Lipopolysaccharide (LPS) molecules are located in the outer leaflet of the outer membrane of bacteria such as Shigella flexneri and Salmonella enterica Typhimurium. LPS molecules are amphipathic and have three regions: lipid A, core sugars, and O antigen polysaccharides. The O antigen polysaccharides of S. flexneri and S. Typhimurium are composed of repeats of a tetrasaccharide unit, and range from 1 to >100 repeat units in length. The length of O antigen polysaccharides is regulated by the activity of Wzz proteins, with different Wzz proteins able to confer different modal length distributions. O antigen polysaccharide chain length impacts on virulence as it affects resistance to Complement, and actin based motility.
Kalynych, S., Morona, R., and Miroslaw, C. (2014) Progress in understanding the assembly process of bacterial O-Antigen. FEMS Microbiol Rev. 2014 Mar 11. doi: 10.1111/1574-6976.12070. [Epub ahead of print]
Tran, E.N.H. and Morona R. (2013) Residues located inside the Escherichia coli FepE protein oligomer are essential for lipopolysaccharide O-antigen modal chain length regulation. Microbiology (SGM). 159: 701-714.
Papadopoulos, M and Morona, R. (2010) Mutagenesis and chemical cross-linking suggest that Wzz dimer stability and oligomerization affect lipopolysaccharide O-antigen modal chain length control. J. Bacteriol. 192: 3385-3393.
Morona, R., Purins, L., Tocilj, A., Matte, A., and Cygler M. (2009) Sequence-structure relationships in polysaccharide co-polymerase (PCP) proteins. Trends Biochem Sci. 34:78-84.
Purins, L., Van Den Bosch, L., and Richardson, V., and Morona, R. (2008) Coiled-coil regions play a role in the function of the Shigella flexneri O-antigen chain length regulator WzzpHS2. Microbiology (SGM) 154:1104-1116.
Tocilj, A., Munger, C., Proteau, A., Morona, R., Purins, L., Ajamina, E., Wagner, J., Papadopoulos, M., Van Den Bosch, L., Rubinstein, J.L., Féthière, J., Matte, A., and Cygler, M. (2008) Bacterial polysaccharide co-polymerases share a common framework for control of polymer length. Nature Struct. Mol. Biol. 15:130-138.
Murray, G.L., Attridge, S.R., and Morona, R. (2006) Altering the length of Salmonella typhimurium lipopolysaccharide O antigen has an impact on interaction with macrophages and complement". J. Bacteriol. 188: 2735-2739.
Murray, G.L., Attridge, S.R., and Morona, R. (2005) "Inducible serum resistance in Salmonella typhimurium is dependent on wzz(fepE)-regulated very long O antigen chains". Microbes Infect. 7: 1296-1304.
Morona, R., Daniels, C., and Van Den Bosch, L. (2003) “Genetic modulation of Shigella flexneri 2a lipopolysaccharide O antigen modal chain length reveals that it has been optimised for virulence.” Microbiology, 49: 925-939.
Murray, G.L., Attridge, S.R., and Morona, R. (2003) “Regulation of Salmonella typhimurium lipopolysaccharide O antigen chain length is required for virulence; identification of FepE as a second Wzz.” Mol. Microbiol. 47: 1395-1406.
Morona, R., and Van Den Bosch, L. (2003) "Lipopolysaccharide O antigen chains mask IcsA(VirG) in Shigella flexneri" FEMS Microbiol. Lett. 221: 173-180.
Morona, R., Van Den Bosch, L., and Daniels, C. (2000) “Evaluation of Wzz/MPA1/MPA2 proteins based on the presence of coiled-coil regions.” Microbiol. 146: 1-4.
Table for this paper.
Baker, S.J., Gunn, J.S. and Morona, R. (1999) “The Salmonella typhi melittin resistance gene pqaB affects intracellular growth in PMA-differentiated U937 cells, polymyxin B resistance, and lipopolysaccharide.” Microbiol. 145: 367-378.
Daniels, C., and Morona, R. (1999) Analysis of Shigella flexneri Wzz (Rol) function by mutagenesis and cross-linking: Wzz is able to oligomerise. Mol. Microbiol. 34: 181-194.
Daniels, C., Vindurampulle, C., and Morona, R. (1998) Overexpression and topology of the Shigella flexneri O-antigen polymerase (Rfc/Wzy). Mol. Microbiol. 28: 1211-1222.
Van Den Bosch, L., Manning, P.A., and Morona, R. (1997) “Regulation of O-antigen chain length is required for Shigella flexneri virulence”. Mol. Microbiol. 23: 765-775.
Outer Membrane Proteins
The outer membrane (OM) of Gram-negative bacteria is in direct contact with the external environment, and contains proteins, lipoproteins, phospholipids, and lipopolysaccharides (LPSs). OM proteins (OMPs) are often directly involved in the virulence of pathogenic bacteria. The Shigella flexneri OMP called IcsA protein is essential for bacterial motility inside infected human cells, while another S. flexneri OMP is IcsP which is a protease that cleaves IcsA.
IcsA and IcsP
The IcsA protein is a large 116 kDa outer membrane protein which is able to interact with actin regulatory proteins within the cytosol of host (human and animal) cells to trigger polymerisation of actin and hence actin-based motility. IcsA is a member of the autotransporter family of proteins, and has an 85 kDa amino terminal passenger (or alpha domain) and a 37 kDa carboxy terminal transporter (or beta domain) that is located in the outer membrane. The IcsA protein is it is targeted to and predominantly localised at the old cell pole in strains that have intact LPS. Polar localisation is relaxed in strains unable to produce either LPS O antigens or the IcsP protease.
Zumsteg, A.B., Goosmann, C., Brinkmann, V., Morona, R., and Arturo Zychlinsky, A. (2014) IcsA is an adhesin in Shigella flexneri that is regulated by the activity of the Type III secretion system. Cell Host and Microbe 15:435-445.
Tran, E.N, Doyle, M.T, and Morona R. (2013) LPS unmasking of Shigella flexneri reveals preferential localisation of tagged outer membrane protease IcsP to septa and new poles. PLoS One. 2013 Jul 25;8(7):e70508. doi: 10.1371/journal.pone.0070508.
Teh, M.Y. and Morona, R. (2013) Identification of Shigella flexneri IcsA residues affecting interaction with N-WASP, and evidence for IcsA-IcsA co-operative interaction. PLoS One. 2013; 8(2):e55152. doi: 10.1371/journal.pone.0055152. Epub 2013 Feb 6.
Teh, M.Y., Tran, E.N., and Morona, R. (2012) Absence of O-antigen suppresses Shigella flexneri IcsA autochaperone region mutations. Microbiology (SGM). 158: 2835-2850.
May, K.L., Grabowicz, M., Polyak, S.W. and Morona, R. (2012) Self-association of the Shigella flexneri IcsA autotransporter. Microbiology (SGM). 158:1874-1883.
Lum, M. and Morona, R. (2012) IcsA autotransporter passenger promotes increased fusion protein expression on the cell surface. Microbial Cell Factories. 11:20. doi: 10.1186/1475-2859-11-20.
May, K.M. and Morona, R. (2008) Mutagenesis of the Shigella flexneri autotransporter IcsA reveals novel functional regions involved in IcsA biogenesis and recruitment of host neural Wiscott-Aldrich syndrome protein. J Bacteriol. 190:4666-4676.
Year Citation 2015 Standish, A., & Morona, R. (2015). Capsule structure, synthesis, and regulation. In J. Brown, S. Hammerschmidt, & C. Orihuela (Eds.), Streptococcus Pneumoniae: Molecular Mechanisms of Host-Pathogen Interactions (pp. 169-179). United Kingdom: Elsevier.
2011 Paton, A., Morona, R., & Paton, J. (2011). Designer Probiotics and Enteric Cytoprotection. In J. Malago, J. Koninkx, & R. Marinsek Logar (Eds.), Probiotic Bacteria and Enteric Infections: Cytoprotection by Probiotic Bacteria (1 ed., pp. 429-444). Netherlands: Springer.
Year Citation 2008 Morona, J. K., Morona, R., & Paton, J. C. (2008). Comparison of Streptococcus pneumoniae Polysaccharide Polymerase Proteins Cps19aI and Cps19fI. Poster session presented at the meeting of FASEB Summer Research Conferences: Microbial Polysaccharides of Medical, Agricultural and Industrial Importance. Carefree, Arizona, USA. 2007 Morona, J. K., Morona, R., & Paton, J. C. (2007). Comparison of Streptococcus pneumoniae Polysaccharide Polymerase Proteins Cps19aI and Cps19fI. Poster session presented at the meeting of Ninth Australian Conference on Molecular Biology of Bacterial Pathogens. Lorne, Victoria, Australia. 2006 Morona, J. K., Morona, R., & Paton, J. C. (2006). Mutation of the Conserved Capsular Polysaccharide Biosynthesis Gene cpsB of Streptococcus pneumoniae D39 results in two distinct CPS phenotypes.. Poster session presented at the meeting of The 5th International Symposium on Pneumococci and Pneumococcal Diseases. Alice Springs, Northern Territory, Australia. 2000 Morona, J. K., Morona, R., Miller, D. C., & Paton, J.C.. (2000). Mutation analysis of the carboxy-terminal [YGX]4 repeat domain of CpsD, a Streptococcus pneumoniae capsule biosynthesis protein. Poster session presented at the meeting of FASEB Summer Research Conferences: Microbial Polysaccharides of Medical, Agricultural and Industrial Importance. Copper Mountain, Colorado, USA. 1999 Morona, J. K., Morona, R., & Paton, J. C. (1999). Comparative genetics of capsular polysaccharide biosynthesis in Streptococcus pneumoniae types belonging to serogroup 19. Poster session presented at the meeting of Fifth Australian Conference on Molecular Analysis of Bacterial Pathogens. Victor Harbor, SA., Australia. 1998 Paton, J. C., Morona, J. K., & Morona, R. (1998). Characterisation of the capsule biosynthesis loci of pneumococci belonging to serogroup 19. Poster session presented at the meeting of First International symposium on Pneumococci and pneumococcal Diseases. Elsinore, Denmark. 1997 Morona, J. K., Morona, R., & Paton, J. C. (1997). Molecular and genetic characterisation of the capsule biosynthesis locus of Streptococcus pneumoniae type 19B. Poster session presented at the meeting of Fourth Australian Conference on Molecular Analysis of Bacterial Pathogens. Jamberoo, NSW. Australia. 1997 Paton, J. C., Morona, J. K., & Morona, R. (1997). Molecular analysis of capsular polysaccharide biosynthesis (cps) loci of Streptococcus pneumoniae.. Poster session presented at the meeting of Microbiology Australia. Adelaide, Australia. 1994 Guidolin, A., Morona, J. K., Morona, R., Hansman, D., & Paton, J. C. (1994). Analysis of genes essential for the production of Streptococcus pneumoniae type 19F capsular polysaccharide. Poster session presented at the meeting of Am. Soc. Microbiol. Fourth Int. Conf. Streptoccocal Genet. Sante Fe, New Mexico, USA. 1994 Guidolin, A., Morona, J. K., Morona, R., Hansman, D., & Paton, J. C. (1994). Nucleotide sequence of genes essential for production of Streptococcus pneumoniae type 19F capsular polysaccharide. Poster session presented at the meeting of Australian Microbiologist. Melbourne, Australia.
Year Citation 2015 Wallace, J., Morona, R., Polyak, S., Booker, G., Abell, A., & Wilce, M. (2015). 9108978, Novel Antimicrobial Compounds. United States of America. 2010 Paton, J., Morona, R., & Paton, A. (2010). 2004201978, Cytotoxin with a Subtilase Domain. Australia. 2006 Paton, A., Morona, R., & Paton, J. (2006). 783536, Recombinant bacterium expressing an oligosaccharide receptor mimic. Australia. 2005 Paton, A., Paton, J., & Morona, R. (2005). Pub no. WO/2005/089775, Treatment and prevention of enterotoxigenic escherichia coli diarrhoeas. Australia.
Course Co-ordinator for Infection and Immunity A III
Current Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2018 Principal Supervisor Enterobacterial Common Antigen Biosynthesis in Shigella Flexneri Doctor of Philosophy Doctorate Full Time Mr Nicholas Tadeusz Maczuga 2017 Principal Supervisor Research on the bacterial strain Shigella Flexneri and Lipolysaccharides Doctor of Philosophy Doctorate Full Time Mr Vincenzo Leo 2016 Principal Supervisor Role of Shigelle Flexner Surface Molecules in Pathogenesis Doctor of Philosophy Doctorate Full Time Mr Jilong Qin
Past Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2014 - 2018 Principal Supervisor Investigation of a Low Molecular Weight Protein Tyrosine Phosphatase in Streptococcus Pneumoniae Doctor of Philosophy Doctorate Full Time Miss Zuleeza Ahmad 2013 - 2015 Principal Supervisor Polarity and Secretion of Shigella flexneri IcsA: A Classical Autotransporter Doctor of Philosophy Doctorate Full Time Mr Matthew Thomas Doyle 2011 - 2015 Principal Supervisor Characterisation of the Shigella flexneri O Antigen Polymerase Wzy Doctor of Philosophy Doctorate Full Time Ms Pratiti Nath 2011 - 2015 Co-Supervisor STAPHYLOCOCCUS AUREUS: STRESS RESPONSE AND ITS ROLES IN PATHOGENESIS Doctor of Philosophy Doctorate Full Time Miss Minh Giao Long Bui 2009 - 2014 Co-Supervisor Coupling Stress Responses and Growth Pathways in Haemophilus influenzae Doctor of Philosophy Doctorate Full Time Mr Changde Donald Jiang 2009 - 2014 Principal Supervisor Identification of host cell proteins involved in Shigella flexneri pathogenesis Doctor of Philosophy Doctorate Full Time Miss Mabel Lum 2009 - 2012 Co-Supervisor Cell Biology of the Interaction between Listeria monocytogenes and Colpoda spp. Doctor of Philosophy Doctorate Full Time Mr Rethish Raghu Nadhanan 2008 - 2012 Co-Supervisor The Role of CpsC in the Regulation of Streptococcus pneumoniae Capsular Polysaccharide Biosynthesis Doctor of Philosophy Doctorate Full Time Mr James Byrne 2007 - 2009 Co-Supervisor Role of pCT0018 for Copper Homeostasis in Listeria monocytogenes Strain DRDC8 Master of Science Master Full Time Miss Mei Mei Hii 2007 - 2013 Principal Supervisor Analysis of Shigella flexneri Cell Surface Virulence Factors Doctor of Philosophy Doctorate Full Time Dr Min Teh 2007 - 2012 Co-Supervisor The Role of YeaZ in the VBNC State of Vibrio parahaemolyticus NCTC 10884 Doctor of Philosophy Doctorate Full Time Mr Shih-Hsun Chen 2006 - 2010 Principal Supervisor Biogenesis of Shigella flexneri IcsA Protein Doctor of Philosophy Doctorate Full Time Mr Marcin Grabowicz 2005 - 2011 Principal Supervisor Characterisation of Shigella flexneri polysaccharide co-polymerase (PCP) protein Wzz Doctor of Philosophy Doctorate Full Time Ms Magdalene Papadopoulos 2004 - 2008 Principal Supervisor Molecular Characterisation of Shigella flexneri Outer Membrane Protease IcsP Doctor of Philosophy Doctorate Part Time Dr Elizabeth Tran 2003 - 2007 Principal Supervisor Molecular Characterisation of Shigella flexneri IcsA and the Role Of Lipopolysaccharide O-Antigen in Actin-based Motility Doctor of Philosophy Doctorate Full Time Dr Kerrie May 2000 - 2005 Co-Supervisor The role of wzz genes in Salmonella typhimurium virulence Doctor of Philosophy Doctorate Full Time Mr Gerald Murray
Date Role Membership Country 2017 - ongoing Member Fellow of the Australian Society for Microbiology (FASM) Australia 1990 - ongoing Member American Society for Microbiology United States
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