Medicine

Event Date: 
Wednesday, March 25, 2015 - 19:00 - 19:45
Institution: 
University of Sydney
Title: 

Poxviruses: Man’s Best Friend. (Or How I Learned to Stop Worrying and Love the Virus)

Abstract: 

 

Poxviruses and humans have had a chequered past. Once the scourge known as smallpox routinely devastated human populations, some estimates are as high as 200 million mortalities last century. However the discovery of a tame version of the virus led to Edward Jenner to demonstrate the practise we now know as vaccination, which has gone some way to repairing the reputation of this virus. My research is built on the premise the these viruses still have much to teach us about many aspects of virology and host cell biology. And one of the most novel and exciting applications may be just around the corner.

 

Event Date: 
Wednesday, March 25, 2015 - 18:15 - 18:30
Institution: 
University of Florida / UWS
Title: 

Candidatus Liberibacter asiaticus encodes a functional salicylic acid hydroxylase which degrades SA and contributes to the suppression of plant defence

Abstract: 

Salicylate (SA) is a plant hormone and plays important roles in plant defence. SA is synthesized in the chloroplast and transmitted in the phloem. SA hydroxylase is a flavoprotein monooxygenase with the enzyme activity of degradation of SA and is a proximal component of the naphthalene degradation pathway in many bacteria. Candidatus Liberibacter asiaticus, the causal agent of the most devastating citrus disease, is phloem limited and encodes a SA hydroxylase. In this study, we have shown that the SA hydroxylase is functional in degrading SA and its analogs. Ca. L. asiaticus infected plants have reduced PR gene (PR1, PR2, and PR5) expression and SA accumulation in Duncan grapefruit and Valencia sweet orange in response to subsequent inoculation with Xanthomonas citri subsp. citri (Xac) Aw, which is nonpathogenic on both citrus varieties. Ca. L. asiaticus also increased citrus susceptibility to subsequent infection by X. citri. The bacterial populations of XacA and XacAw in grapefruit were significantly higher in Ca. L. asiaticus infected plants compared to healthy control. Our data suggest that Ca. L. asiaticus encodes a functional salicylic acid hydroxylase which degrades SA and contributes to the suppression of plant defence. To counteract this virulence mechanism of Ca. L. asiaticus, foliar spray of SA analogs 2, 6-Dichloroisonicotinic acid (INA) and 2,1,3-Benzothiadiazole (BTH) and SA producing bacterial isolates was conducted to control HLB in large scale field trials. Both INA and BTH in combination with selected bacterial strains slowed down the increase of Ca. L. asiaticus titers in planta and HLB disease severity compared to negative control. SA hydroxylase seems to be an ideal target to develop small molecule inhibitors since no human homolog is present and it is not essential for bacterial growth, hence, the possibility of resistance development is minimized.      Salicylate (SA) is a plant hormone and plays important roles in plant defence. SA is synthesized in the chloroplast and transmitted in the phloem. SA hydroxylase is a flavoprotein monooxygenase with the enzyme activity of degradation of SA and is a proximal component of the naphthalene degradation pathway in many bacteria. Candidatus Liberibacter asiaticus, the causal agent of the most devastating citrus disease, is phloem limited and encodes a SA hydroxylase. In this study, we have shown that the SA hydroxylase is functional in degrading SA and its analogs. Ca. L. asiaticus infected plants have reduced PR gene (PR1, PR2, and PR5) expression and SA accumulation in Duncan grapefruit and Valencia sweet orange in response to subsequent inoculation with Xanthomonas citri subsp. citri (Xac) Aw, which is nonpathogenic on both citrus varieties. Ca. L. asiaticus also increased citrus susceptibility to subsequent infection by X. citri. The bacterial populations of XacA and XacAw in grapefruit were significantly higher in Ca. L. asiaticus infected plants compared to healthy control. Our data suggest that Ca. L. asiaticus encodes a functional salicylic acid hydroxylase which degrades SA and contributes to the suppression of plant defence. To counteract this virulence mechanism of Ca. L. asiaticus, foliar spray of SA analogs 2, 6-Dichloroisonicotinic acid (INA) and 2,1,3-Benzothiadiazole (BTH) and SA producing bacterial isolates was conducted to control HLB in large scale field trials. Both INA and BTH in combination with selected bacterial strains slowed down the increase of Ca. L. asiaticus titers in planta and HLB disease severity compared to negative control. SA hydroxylase seems to be an ideal target to develop small molecule inhibitors since no human homolog is present and it is not essential for bacterial growth, hence, the possibility of resistance development is minimized.      

Event Date: 
Wednesday, February 25, 2015 - 17:30 - 18:00
Institution: 
University of Melbourne
Title: 

Genomic epidemiology of antibiotic resistant bacteria

Abstract: 

Microbial populations contribute to human disease in a variety of ways, both as agents of infection and as healthy components of the microbiome. Genomic approaches can offer deep insights into this hidden microbial world, including revealing the composition of microbial communities, tracking the movement of individual organisms, and illuminating evolutionary changes. Here I will present recent work applying genomic epidemiology to investigate the emergence and spread of antibiotic resistance in a range of important pathogens, including typhoid, dysentery and the emerging hospital superbug Klebsiella.

Event Date: 
Wednesday, October 29, 2014 - 19:00 - 19:30
Institution: 
UTS
Title: 

“On the value of reframing antibiotic resistance as a disaster risk problem”

Abstract: 

Dr. Maurizio Labbate1,2 & A/Prof. Dale Dominey-Howes3

1School of Medical and Molecular Biosciences, University of Technology, Sydney, Australia.
2The ithree Institute, University of Technology, Sydney, Australia.
3Asia – Pacific Natural Hazards Research Group, School of Geosciences, University of Sydney, Australia.

Abstract:

On the 1st May 2014 the World Health Organization in its first global assessment of antimicrobial resistance reported that antibiotic resistance has now reached alarming proportions and is no longer a future problem but a contemporary reality. This comes off the back of other urgent calls from leading authorities including the Deputy Director of the Center for Disease Control (CDC) who has publicly stated that we have now reached the “end of the antibiotic era” and the UK Chief Medical Officer, Professor Dame Sally Davies who called for antibiotic resistance to be placed on the risk register above the issue of terrorism. Increasingly, the tone of the language used by these organizations and individuals is reminiscent of that used by the disaster and emergency risk management communities to describe commonly occurring disasters such as earthquakes, fires, floods and storms.

Antibiotic resistant infections are rising fast and affect millions of people globally. Antibiotic resistance has become a slow onset disaster that like climate change has struggled to elicit the sort of coordinated international response that is required to deal with the magnitude of the emergency. Anthropogenic modification of the Earth’s climate system provides the foundation for sudden onset natural disasters such as hurricanes, wildfires and storms. Likewise, increasingly widespread antibiotic resistance is laying the foundation for the future occurrence of sudden onset bacterial epidemic and pandemic disasters.

Despite the finest efforts by medical and health policy makers and communities to control the antibiotic resistance problem, the issue has reached a critical tipping point. Given the current state of the antibiotic resistance problem and the likely near future of untreatable bacterial infections, we propose an alternative and novel policy perspective. With this is mind, we propose to make antibiotic a broader issue and reframe it as a disaster risk problem and engage the expertise of emergency managers. Governments and disaster policy makers across the world use the Emergency Risk Management process in the management of and preparation for natural disasters. This process is a systematic method that through engagement with multiple stakeholders identifies, analyses, evaluates and treats risks and takes an iterative approach with well-defined activities that lead to implementation of risk-treatment strategies tailored to a specific community’s risk profile. This policy and practice framework is an excellent mechanism for reaching out to communities and communicating complex messages – an area that needs to be enhanced.

Event Date: 
Wednesday, September 24, 2014 - 18:15 - 18:30
Institution: 
University of Sydney
Title: 

Cathelicidins in the Tasmanian devil (Sarcophilus harrisii)

Abstract: 

Antimicrobial resistance is increasing, posing a threat to human and animal health. A lack of new antibiotics means alternatives such as antimicrobial peptides are urgently required. Antimicrobial peptides are a primitive component of the innate immune system. Cathelicidins are a predominant family within mammals, contributing to host immunity through antimicrobial and immunomodulatory functions. They have been studied extensively in eutherian mammals but marsupials are relatively unexplored. Marsupials give birth to altricial young which are immunologically naïve. During development the young are protected from infection by mechanisms such as cathelicidins within the pouch. This unique reproductive physiology has encouraged lineage specific expansion of the cathelicidin gene family within marsupials, resulting in numerous diverse peptides.
 
The Tasmanian devil (Sarcophilus harrisii) is the largest remaining carnivorous marsupial and is currently under threat from a contagious cancer, devil facial tumour disease (DFTD). Human and bovine cathelicidins exhibit anti-tumour activity against a number of cancers. Furthermore, studies in the tammar wallaby have revealed the potency of marsupial cathelicidins against multi-drug resistant bacteria. As such, release of the Tasmanian devil genome in 2012 provides new avenues in the search for cathelicidins with the therapeutic potential to treat DFTD and resistant pathogens.
 
We identified 7 cathelicidins in the Tasmanian devil genome which were highly variable and distantly related to eutherian cathelicidins. Six Tasmanian devil cathelicidins have been synthesised and will be tested against a range of bacteria and fungi. Preliminary antifungal testing of two cathelicidins revealed that one peptide was more effective at killing Candida krusei, Candida parapsilosisCryptococcus gattii and Cryptococcus neoformans than the antifungal drug fluconazole. Cytotoxic and haemolytic activity of all six cathelicidins has also been determined. Four cathelicidins did not kill human lung epithelial cells or red blood cells, and only two showed moderate cytotoxic and haemolytic activity. This study highlights the potential for marsupials such as the Tasmanian devil to provide new drugs to treat human and animal disease.

Event Date: 
Wednesday, June 25, 2014 - 19:00 - 20:00
Institution: 
UTS
Title: 

Honey: Return of an Ancient Remedy

Abstract: 

Chronic wounds are a tremendous burden to human health worldwide, currently affecting 2% of the population in developed countries, with significant social and economic costs. Treatment of these wounds is becoming increasingly difficult due to infections caused by multidrug resistant bacteria. Honey is increasingly being used as a topical treatment for these wounds. New Zealand manuka honey has potent broad-spectrum antimicrobial activity and resistance to honey has not been attainable in the laboratory. Approved medical-grade manuka honey and honey dressings are readily available for use in wound treatment but their use is limited, largely due to lack of information about how they work. This talk will provide an overview of where we are at with research examining the value of honey as an antibacterial agent in wound treatment. It will include how different bacteria respond to honey, synergistic interaction studies using manuka honey and antibiotics currently used to treat infected wounds, and biofilm prevention and eradication studies.

Event Date: 
Wednesday, October 30, 2013 - 18:15 - 18:30
Institution: 
USyd
Title: 

Norovirus Sydney 2012: The chunder from down under

Abstract: 

Norovirus is the leading cause of acute gastroenteritis globally with the primary symptoms of infection including vomiting and diarrhea. Typical of most single stranded RNA viruses, norovirus demonstrates a broad genetic diversity and can infect a wide range of mammalian hosts; however, the majority of human infections are caused by variants of a single genetic lineage – GII.4. The molecular epidemiology of the norovirus GII.4 lineage has been characterised by a continual turnover of novel variants that often precede large global epidemics. The emergence and evolution of these novel GII.4 variants has been attributed to rapid evolution and antigenic variation in response to herd immunity as well as frequent recombination between circulating strains. In this presentation, I will reflect on the recent molecular epidemiology of norovirus infections in Australia and globally, and then discuss the significant impact and origins of a recently emerged GII.4 virus, known as Sydney 2012, that has grabbed headlines across the globe (for the wrong reasons).

Event Date: 
Wednesday, August 28, 2013 - 19:00 - 20:00
Institution: 
iThree Institute UTS
Title: 

Genome plasticity in Vibrio species – how lateral gene transfer directs niche specialisation and pathogenicity

Abstract: 

Bacteria of the Vibrio genus are abundant in aquatic environments, fulfil important nutrient cycling roles and are often found in association with marine animals such as corals, molluscs, sponges, crustaceans and fish. This diversity in niche occupation is a feature of Vibrio species and is largely (or at least in significant part) driven by lateral gene transfer (LGT). LGT is a two-step process firstly requiring physical transfer of DNA from one bacterial cell to another followed by subsequent integration of the transferred DNA into the genome thus allowing stable inheritance and expression. Numerous mechanisms for integration exist such as homologous recombination and a wide-range of diverse genetic elements such as transposons, integrative conjugative elements, prophages and integrons. Using two Vibrios species, V. rotiferianus and V. cholerae, research in our laboratory has sought to understand how mobile DNA contributes to vibrio evolution, niche specialisation and pathogenicity. In V. rotiferianus, we have been researching the integron, a genetic element that contributes up to 3% of a vibrios genome in laterally acquired mobile DNA. This region is dynamic and evolves at a faster rate than mutation. Our research has shown that this region provides the organism a mechanism for reworking surface polysaccharide affecting biofilm formation and potentially interactions with higher organisms. Furthermore, we have been researching evolution in V. cholerae isolated from Sydney estuarine waters. These isolates are pathogenic in animal models with all lacking the usual virulence factors of cholera toxin and colonisation factor tcpA and most lacking type III secretion indicating the presence of novel virulence factors. One isolate we are focussing on contains a novel 32-kb mobile element inserted into the indigenous recA but carries a unique recA with only 80% identity to other V. cholerae recA genes. Overall, our research demonstrates the plasticity of vibrio genomes and the significant contribution that LGT makes to the continuing evolution to the Vibrio genus.

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