I am a Cochlear Pty Ltd Fellow working at the ithree institute (infection, immunity and innovation) at the University of Technology Sydney (UTS).
I have been trained as an environmental microbiologist at the University of New South Wales and graduated with a PhD in Microbiology in 2004. My PhD looked at the toxins produced by blue green algae.
After my PhD i joined a team at UTS interested in medical microbiology. Since then i have developed a deep interest in biofilms and lung infections caused by pathogenic bacteria.
During my first postdoc I looked at biofilms caused by of Haemophilus influenzae , identifying methods that will help the medical field eradicate infections caused by this particular bacterium.
At the end of my first postdoc my role changed slightly and I was appopinted as a first ever Cochlear fellow. My responsibilities included developing techniques to handle explanted medical devices and finding the best storage conditions to allow transport of devices worldwide and ultimately permit analyses of biofilms attached to explanted devices (infections).
My research has been original and is now internationally regarded amongst clinicians. Over the last 5 years I have developed innovative ideas to grow biofilms in vitro.
My research interests the study and visualisation of bacterial biofilms on medical devices.
Loo, C.Y., Rohanizadeh, R., Young, P.M., Traini, D., Cavaliere, R., Whitchurch, C.B. & Lee, W.H. 2016, 'Combination of Silver Nanoparticles and Curcumin Nanoparticles for Enhanced Anti-biofilm Activities.', Journal of agricultural and food chemistry, vol. 64, pp. 2513-2522.View/Download from: UTS OPUS or Publisher's site
Biofilm tolerance has become a serious clinical concern in the treatment of nosocomial pneumonia owing to the resistance to various antibiotics. There is an urgent need to develop alternative antimicrobial agents or combination drug therapies that are effective via different mechanisms. Silver nanoparticles (AgNPs) have been developed as an anti-biofilm agent for the treatment of infections associated with the use of mechanical ventilations, such as endotracheal intubation. Meanwhile curcumin, a phenolic plant extract, has displayed natural anti-biofilm properties through the inhibition of bacterial quorum sensing systems. The aim of this study was to investigate the possible synergistic/additive interactions of AgNPs and curcumin nanoparticles (Cur-NPs) against both Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) microorganisms. The combination of AgNPs and Cur-NPs (termed Cur-SNPs) at 100 g/mL disrupted 50% of established bacterial biofilms (formed on microtiter plates). However, further increase in the concentration of Cur-SNPs failed to effectively eliminate the biofilms. To achieve the same effect, at least 500 g/mL Cur-NP alone was needed. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) revealed that combination therapy (Cur-SNPs) was the most potent to eradicate preformed biofilm compared to monodrug therapy. These agents are also nontoxic to healthy human bronchial epithelial cells (BEAS2B).
Turnbull, L., Toyofuku, M., Hynen, A.L., Kurosawa, M., Pessi, G., Petty, N.K., Osvath, S.R., Carcamo-Oyarce, G., Gloag, E.S., Shimoni, R., Omasits, U., Ito, S., Yap, X., Monahan, L.G., Cavaliere, R., Ahrens, C.H., Charles, I.G., Nomura, N., Eberl, L. & Whitchurch, C.B. 2016, 'Explosive cell lysis as a mechanism for the biogenesis of bacterial membrane vesicles and biofilms', NATURE COMMUNICATIONS, vol. 7.View/Download from: UTS OPUS or Publisher's site
Loo, C.-.Y., Lee, W.-.H., Young, P.M., Cavaliere, R., Whitchurch, C.B. & Rohanizadeh, R. 2015, 'Implications and emerging control strategies for ventilator-associated infections', EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, vol. 13, no. 3, pp. 379-393.View/Download from: UTS OPUS or Publisher's site
Loo, J., Lee, W.-.H., Young, P.M., Traini, D., Cavaliere, R., Whitchurch, C.B. & Rohanizadeh, R. 2015, 'CURCUMIN AND SILVER NANOPARTICLE HYDROGELS FOR ENDOTRACHEAL TUBE-ASSOCIATED INFECTIONS: CHARACTERIZATION AND ANTI-BIOFILM ACTIVITIES', JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, vol. 28, no. 3, pp. A15-A15.View/Download from: UTS OPUS
Nolan, L.M., Cavaliere, R., Turnbull, L. & Whitchurch, C.B. 2015, 'Extracellular ATP inhibits twitching motility-mediated biofilm expansion by Pseudomonas aeruginosa.', BMC Microbiology, vol. 15, pp. 1-12.View/Download from: UTS OPUS or Publisher's site
Pseudomonas aeruginosa is an opportunistic pathogen that exploits damaged epithelia to cause infection. Type IV pili (tfp) are polarly located filamentous structures which are the major adhesins for attachment of P. aeruginosa to epithelial cells. The extension and retraction of tfp powers a mode of surface translocation termed twitching motility that is involved in biofilm development and also mediates the active expansion of biofilms across surfaces. Extracellular adenosine triphosphate (eATP) is a key "danger" signalling molecule that is released by damaged epithelial cells to alert the immune system to the potential presence of pathogens. As P. aeruginosa has a propensity for infecting damaged epithelial tissues we have explored the influence of eATP on tfp biogenesis and twitching motility-mediated biofilm expansion by P. aeruginosa.In this study we have found that eATP inhibits P. aeruginosa twitching motility-mediated expansion of interstitial biofilms at levels that are not inhibitory to growth. We have determined that eATP does not inhibit expression of the tfp major subunit, PilA, but reduces the levels of surface assembled tfp. We have also determined that the active twitching zone of expanding P. aeruginosa interstitial biofilms contain large quantities of eATP which may serve as a signalling molecule to co-ordinate cell movements in the expanding biofilm. The inhibition of twitching motility-mediated interstitial biofilm expansion requires eATP hydrolysis and does not appear to be mediated by the Chp chemosensory system.Endogenous eATP produced by P. aeruginosa serves as a signalling molecule to co-ordinate complex multicellular behaviours of this pathogen. Given the propensity for P. aeruginosa to infect damaged epithelial tissues, our observations suggest that eATP released by damaged cells may provide a cue to reduce twitching motility of P. aeruginosa in order to establish infection at the site of damage. Furthermore, eATP produced by P. aerugino...
Loo, C.-.Y., Young, P.M., Cavaliere, R., Whitchurch, C.B., Lee, W.-.H. & Rohanizadeh, R. 2014, 'Silver nanoparticles enhance Pseudomonas aeruginosa PAO1 biofilm detachment', DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, vol. 40, no. 6, pp. 719-729.View/Download from: UTS OPUS or Publisher's site
Loo, C.-.Y., Young, P.M., Lee, W.-.H., Cavaliere, R., Traini, D., Whitchurch, C.B. & Rohanizadeh, R. 2014, 'Non-cytotoxic silver nanoparticle-polyvinyl alcohol hydrogels with anti-biofilm activity: designed as coatings for endotracheal tube materials', Biofouling, vol. 30, no. 7, pp. 773-788.View/Download from: UTS OPUS or Publisher's site
Endotracheal intubation is commonly associated with hospital-acquired infections as the intubation device acts as reservoir for bacterial colonization in the lungs. To reduce the incidence of bacterial colonization on the tubes, hydrogel coatings loaded with antimicrobial agents are gaining popularity. The aim of this study was to incorporate silver nanoparticles (AgNPs) into polyvinyl alcohol (PVA) to form stable hydrogels. Embedding AgNPs into PVA resulted in a decreased elongation at break and an increased tensile strength compared to PVA alone. The Ag release profile varied as a function of the degree of hydrolysis of PVA: the higher degree of hydrolysis demonstrated a lower release rate. Fourier infrared transform spectroscopy demonstrated that AgNPs interacted exclusively with the –OH groups of PVA. AgNP-loaded PVA was non-toxic against human normal bronchial epithelial cells while effective against the attachment of Pseudomonas aeruginosa and Staphylococcus aureus with a greater effect on P. aeruginosa.
Loo, C.-.Y., Young, P.M., Lee, W.-.H., Cavaliere, R., Traini, D., Whitchurch, C.B. & Rohanizadeh, R. 2014, 'NON-CYTOTOXIC SILVER NANOPARTICLES-POLYVINYL ALCOHOL HYDROGELS WITH ANTI-BIOFILM ACTIVITY AS COATINGS FOR ENDOTRACHEAL TUBE MATERIALS', Biofouling, vol. 30, no. 7, pp. 773-788.
Loo, C.-.Y., Young, P.M., Lee, W.-.H., Traini, D., Cavaliere, R., Whitchurch, C.B. & Rohanizadeh, R. 2014, 'COMBINATION THERAPY OF CURCUMIN AND SILVER NANOPARTICLES WITH ENHANCED ANTI-BIOFILM ACTIVITY FOR TREATMENT OF ENDOTRACHEAL TUBE-ASSOCIATED INFECTIONS', JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, vol. 27, no. 4, pp. A17-A18.View/Download from: UTS OPUS
Cavaliere, R., Ball, J.L., Turnbull, L. & Whitchurch, C.B. 2014, 'The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin', Microbiology Open, vol. 3, no. 4, pp. 557-567.View/Download from: UTS OPUS or Publisher's site
Nontypeable Hemophilus influenzae (NTHi) is a Gram-negative bacterial pathogen that causes chronic biofilm infections of the ears and airways. The biofilm matrix provides structural integrity to the biofilm and protects biofilm cells from antibiotic exposure by reducing penetration of antimicrobial compounds into the biofilm. Extracellular DNA (eDNA) has been found to be a major matrix component of biofilms formed by many species of Gram-positive and Gram-negative bacteria, including NTHi. Interestingly, the cation chelator ethylenediaminetetra-acetic acid (EDTA) has been shown to reduce the matrix strength of biofilms of several bacterial species as well as to have bactericidal activity against various pathogens. EDTA exerts its antimicrobial activity by chelating divalent cations necessary for growth and membrane stability and by destabilizing the matrix thus enhancing the detachment of bacterial cells from the biofilm. In this study, we have explored the role of divalent cations in NTHi biofilm development and stability. We have utilized in vitro static and continuous flow models of biofilm development by NTHi to demonstrate that magnesium cations enhance biofilm formation by NTHi. We found that the divalent cation chelator EDTA is effective at both preventing NTHi biofilm formation and at treating established NTHi biofilms. Furthermore, we found that the matrix destablilizers EDTA and DNaseI increase the susceptibility of NTHi biofilms to ampicillin and ciprofloxacin. Our observations indicate that DNaseI and EDTA enhance the efficacy of antibiotic treatment of NTHi biofilms. These observations may lead to new strategies that will improve the treatment options available to patients with chronic NTHi infections.
Gloag, E.S., Turnbull, L., Huang, A., Vallotton, P., Wang, H., Nolan, L.M., Mililli, L., Hunt, C., Lu, J., Osvath, S.R., Monahan, L.G., Cavaliere, R., Charles, I.G., Wand, M., Gee, M., Ranganathan, P. & Whitchurch, C.B. 2013, 'Self-organization of bacterial biofilms is facilitated by extracellular DNA', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 28, pp. 11541-11546.View/Download from: UTS OPUS or Publisher's site
Twitching motility-mediated biofilm expansion is a complex, multicellular behavior that enables the active colonization of surfaces by many species of bacteria. In this study we have explored the emergence of intricate network patterns of interconnected trails that form in actively expanding biofilms of Pseudomonas aeruginosa. We have used high-resolution, phase-contrast time-lapse microscopy and developed sophisticated computer vision algorithms to track and analyze individual cell movements during expansion of P. aeruginosa biofilms. We have also used atomic force microscopy to examine the topography of the substrate underneath the expanding biofilm. Our analyses reveal that at the leading edge of the biofilm, highly coherent groups of bacteria migrate across the surface of the semisolid media and in doing so create furrows along which following cells preferentially migrate. This leads to the emergence of a network of trails that guide mass transit toward the leading edges of the biofilm. We have also determined that extracellular DNA (eDNA) facilitates efficient traffic flow throughout the furrow network by maintaining coherent cell alignments, thereby avoiding traffic jams and ensuring an efficient supply of cells to the migrating front. Our analyses reveal that eDNA also coordinates the movements of cells in the leading edge vanguard rafts and is required for the assembly of cells into the bulldozer aggregates that forge the interconnecting furrows. Our observations have revealed that large-scale self-organization of cells in actively expanding biofilms of P. aeruginosa occurs through construction of an intricate network of furrows that is facilitated by eDNA
Baldi, D.L., Higginson, E.E., Hocking, D.M., Praszkier, J., Cavaliere, R., James, C.E., Bennett-Wood, V., Azzopardi, K.I., Turnbull, L., Lithgow, T., Robins-Browne, R.M., Whitchurch, C.B. & Tauschek, M. 2012, 'The type II secretion system and its ubiquitous lipoprotein substrate, SslE, are required for biofilm formation and virulence of enteropathogenic Escherichia coli', Infection and Immunity, vol. 80, no. 6, pp. 2042-2052.View/Download from: Publisher's site
Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrhea in infants in developing countries. We have identified a functional type II secretion system (T2SS) in EPEC that is homologous to the pathway responsible for the secretion of heat-labile enterotoxin by enterotoxigenic E. coli. The wild-type EPEC T2SS was able to secrete a heat-labile enterotoxin reporter, but an isogenic T2SS mutant could not. We showed that the major substrate of the T2SS in EPEC is SslE, an outer membrane lipoprotein (formerly known as YghJ), and that a functional T2SS is essential for biofilm formation by EPEC. T2SS and SslE mutants were arrested at the microcolony stage of biofilm formation, suggesting that the T2SS is involved in the development of mature biofilms and that SslE is a dominant effector of biofilm development. Moreover, the T2SS was required for virulence, as infection of rabbits with a rabbit-specific EPEC strain carrying a mutation in either the T2SS or SslE resulted in significantly reduced intestinal colonization and milder disease. © 2012, American Society for Microbiology.
Loo, C., Lee, W.B., Cavaliere, R., Whitchurch, C.B. & Rohanizadeh, R. 2012, 'Superhydrophobic, Nanotextured Polyvinyl Chloride Films For Delaying Pseudomonas Aeruginosa Attachment To Intubation Tubes And Medical Plastics', Acta Biomaterialia, vol. 8, no. 5, pp. 1881-1890.View/Download from: UTS OPUS or Publisher's site
Bacterial attachment onto the surface of polymers in medical devices such as polyvinyl chloride (PVC) is influenced by the physicochemical properties of the polymer, including its surface hydrophobicity and roughness. In this study, to prevent biofilm fo
Baldi, D.L., Higginson, E., Hocking, D., Praszkier, J., Cavaliere, R., James, C.E., Bennett-wood, V., Azzopardi, K., Turnbull, L., Lithgow, T., Robins-Browne, R., Whitchurch, C.B. & Tauschek, M. 2012, 'The Type Ii Secretion System And Its Ubiquitous Lipoprotein Substrate, Ssle, Are Required For Biofilm Formation And Virulence Of Enteropathogenic Escherichia Coli', Infection And Immunity, vol. 80, no. 6, pp. 2042-2052.View/Download from: UTS OPUS or Publisher's site
Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrhea in infants in developing countries. We have identified a functional type II secretion system (T2SS) in EPEC that is homologous to the pathway responsible for the secretion of heat-labi
Baldi, D.L., Higginson, E.E., Hocking, D.M., Praszkier, J., Cavaliere, R., James, C.E., Bennett-Wood, V., Azzopardi, K.I., Turnbull, L., Lithgow, T., Robins-Browne, R.M., Whitchurch, C.B. & Tauschek, M. 2012, 'The Type II Secretion System and Its Ubiquitous Lipoprotein Substrate, SslE, Are Required for Biofilm Formation and Virulence of Enteropathogenic Escherichia coli', INFECTION AND IMMUNITY, vol. 80, no. 6, pp. 2042-2052.View/Download from: Publisher's site
Wilksch, J.J., Yang, J., Clements, A., Gabbe, J.L., Short, K.R., Cao, H., Cavaliere, R., James, C.E., Whitchurch, C.B., Schembri, M.A., Chuah, M.L.C., Liang, Z.-.X., Wijburg, O.L., Jenney, A.W., Lithgow, T. & Strugnell, R.A. 2011, 'MrkH, a Novel c-di-GMP-Dependent Transcriptional Activator, Controls Klebsiella pneumoniae Biofilm Formation by Regulating Type 3 Fimbriae Expression', PLOS PATHOGENS, vol. 7, no. 8.View/Download from: UTS OPUS or Publisher's site
Cavaliere, R. 2004, 'Evidence for differences in the metabolism of saxitoxin and C1+2 toxins in the freshwater cyanobacterium Cylindrospermopsis raciborskii T3', Biochimica et Biophysica Acta (BBA), vol. 1674, no. 1, pp. 60-67.