Original Publication Date: 4 April, 2017
Publication / Source: Infectious Diseases Hub
Authors: Ruth Neale (Community for Open Antimicrobial Drug Discovery, Brisbane, Australia)
Well readers, talk about starting day two of SDRI 2017 off with a bang!
The day began with Ramanan Laxminarayan from the Center for Disease Dynamics, Economics & Policy (CDDEP), Public Health Foundation Indian (PHFI) and Princeton! His long standing experience in advisory work at an international level for the WHO, World Bank and his amazing and unique set of skills – mixing economics and epidemiology – made an inspirational plenary talk to kick off day two.
Ramanan’s 20 years of antimicrobial resistance (AMR) research helped bring AMR before the United Nations General Assembly (UNGA) with Sally Davies, Chief Medical Officer for England, last September. His research deals with the integration of epidemiological models of infectious diseases and drug resistance into the economic analysis of public health problems. He has worked to improve understanding of drug resistance as a problem of managing a shared global resource – his TED talk is worth watching!
His plenary talk finished explaining how we might leverage the momentum achieved through the UNGA AMR meeting to develop realistic goals, stimulate political will, mobilize resources, and agree on an accountability mechanism for global collective action on this issue.
For everyone involved, it is clear that ambitious, collaborative actions is urgently required internationally for combating drug-resistant bacteria. Up next was the international models and funding session, keeping with the theme of global action against AMR. SDRI 2017 co-chair Jian Li (Monash University) chaired this unique session which highlighted the research agendas of a range of key agencies involved in AMR. The speakers discussed strategies and funding models responding to the most pressing problems caused by AMR, with a session goal of providing access to future points of interaction with these major funding bodies for grant opportunities.
Head of Drug-Resistant Infections at the Wellcome Trust (London, UK), Tim Jinks, first presented the core set of coordinated AMR activities at the Wellcome Trust, including their recent announcement of 11 funded projects through CARB-X, global antibacterial innovation initiative. Jinks also highlighted CARB-X ED – a fantastic educational opportunity including workshops on antibiotic drug development.
Barbara Kerstiëns (EU Commission), presented a summary of the European funding designed to stimulate research and innovation in AMR, including Innovative Medicines Initiative. Zuoyu Xu described mission of the National Institute of Health’s National Institute of Allergy and Infectious Disease (NIH NIAID; MD, USA) program in the USA. Anne Kelso from the National Health Medical Research Council (NHMRC; Canberra) presented opportunities and mechanisms to translate AMR research in Australia.
The second antimicrobial drug discovery session commenced chaired by SDRI co-chair Matthew Cooper from The University of Queensland (UQ). The theme for SDRI 2017 is New Drugs for drug-resistant infections – highlighting the global importance of early discovery research in industry and academia to lead to new drugs, making the drug discovery sessions an important cornerstone to the conference.
Michelle Wykes from Brisbane’s QIMR Berghofer studies the mechanisms by which Plasmodium spp, the causative agents of malaria, are able to evade immunity. She also went on to describe a novel immunotherapy for treating malaria recently published in Immunity.
University of California San Diego’s Joe Pogliano (CA, USA) spoke next about his research on utilizing cell biological tools to study the recently discovered phage nucleus and to understand the mechanisms of action of new antibiotics. His team developed Bacterial Cytological Profiling (BCP) technology that provides a rapid method for screening antibiotics against multi-drug resistant bacteria and understanding their mechanisms of action. Pogliano also founded Linnaeus Bioscience, Inc. (CA, USA) to commercialize this technology.
It was great to hear from Qin Cheng next from the Drug Resistance and Diagnostic department at the Australian Army Malaria Institute (Enoggera, Australia). Cheng is frequently invited as a Temporary Adviser to the WHO to evaluate malaria diagnostics and monitor malaria drug resistance.
Her expert talk on malaria drug resistance focused on targeting active metabolic pathways to interrupt artemisinin-induced dormancy. P. falciparum parasites arrest their growth and development after a short exposure to artemisinin derivatives in vitro. Identification of metabolic pathways that remain active in dormant parasites not only helps understand underlying mechanisms supporting dormant parasites, but also reveals potential targets for killing dormant parasites.
Enthusiastic Richard Payne from the University of Sydney (Australia) closed the session by highlighting his team’s recently published work in Nature Communications, exploring uridylpeptide natural products as inspiration for the development of tuberculosis drug leads.
The last session of the day was alternate therapies chaired by Elizabeth Harry – world leader in the field of bacterial cell division – from the University of Technology Sydney (Australia). Antibiotics are not the only approach to treating infections, and the rise of resistance has led to a renewed focus on alternate therapies, including antibody-based therapeutics, stimulation of the immune response, probiotic approaches to alter the microbiome, phage therapy and other treatments.
Working in antibiotic drug discovery, I was not too familiar with alternate therapies so in preparation for this session, I read The Lancet Infectious Disease article on alternatives to antibiotics. The article involved a number of SDRI 2017 invited speakers as authors including the first speaker for this session.
I was incredibly excited to hear world expert Robert Hancock (University of British Columbia, Vancouver, Canada). His research team have developed novel anti-biofilm peptides to kill drug-resistant bacteria. Hancock believes it is imperative to consider alternatives to conventional antibiotic strategies and particularly for infections that are recalcitrant to current therapies (e.g. sepsis and chronic biofilm infections).
Gilda Tachedjian from the Burnet Institute (Melbourne, Australia) was up next with her talk on the role of microbiota metabolites in maintaining vaginal health. Organic acid metabolites produced by the vaginal microbiota have reported antimicrobial and immune-modulatory activities, suggesting their potential role in modulating susceptibility to sexually transmitted infections, including the viral pathogen HIV. Tachedjian’s research findings highlight the potential use of lactic acid in producing probiotics in the lower female reproductive tract as an adjunct to antivirals and antibiotics in maintaining vaginal health.
This talk was followed by Herbert Schweizer at the University of Florida (FL, USA). β-Lactams are front-line broad-spectrum bactericidal antibiotics useful for treatment of infections caused by Gram-negative bacteria. Schweizer presented his work into optimized non-genetic β-lactam resistance dissemination caused by outer membrane vesicle secreted lipidated β-lactamase.
Bacteriophage science expert – Sandra Morales from AmpliPhi Biosciences (MA, USA) followed this. Morales explained that bacteriophages (phages) are highly specific bacterial viruses that are intelligent agents that are able to “out-mutate the mutators”. Morales’ talk concentrated on results from pre-clinical and human clinical trials, and the issues facing the fledgling phage therapy industry such as production, regulatory, and financial constraints. New developments in the combined use of phages and antibiotics was also described which offered the tantalizing possibility that phage therapy might not only be able to contain antibiotic resistant bacteria but even reverse it – an ideal partner for the multi drug-resistant era, indeed!
Elizabeth Harry received global media coverage at the end of last year on her research published into the use of Manuka honey to treat drug-resistant infections. Harry was up next and presented this topical solution.
The session, and talks for day two, closed with a rapid fire talk on inducing host cell death to combat infections. Thomas Naderer has devised an innovative strategy to combat intracellular infections, by focusing on host survival proteins with his team at Monash University (Melbourne, Australia).
Another stimulating poster session followed the talks for the day. I enjoyed meeting Amy Cain during the poster presentation who told me about her research into Transposon Directed Insertion sequencing (TraDIS) to investigate genes required for survival during antimicrobial synergy in multidrug-resistant Klebsiella pneumoniae.
At the end of the day, delegates eagerly met up with colleagues and friends to discuss the day’s event at the reception which started on the terrace – followed by the conference dinner, featuring a beautiful performance from two 10-year-old world famous pianists based in Brisbane. The one thing that stuck out from this evening was my conversation with global anti-infectives expert John Rex and antibacterial discovery expert Jennifer Leeds (from Norvatis) who both said they ‘bow down’ to chemists, and have the most utmost respect for anyone trained in chemistry – “they are the miracle workers when it comes to antibiotic drug discovery.”
I am very much looking forward to day three (our final day!) kicking off with John Rex who has 30 years’ experience in antimicrobial drug discovery. Look out for my final post for SDRI 2017 tomorrow.
If you missed Ruth’s blog from day one catch up here!
About the author
I am the Outreach Program Coordinator for a global open-access antibiotic drug discovery initiative called the Community for Open Antimicrobial Drug Discovery (CO-ADD). We launched in February 2015 to uncover significant and rich chemical diversity held outside of corporate compound collections. CO-ADD has developed a collaborative pipeline of new antibiotic candidates through the provision of free and timely antimicrobial screening to academic researchers around the world. CO-ADD tests compounds against five of the top pathogens listed on the WHO priority list for Research and Development of new antibiotics, as well as two fungi. CO-ADD is based at The University of Queensland (UQ) Institute for Molecular Bioscience.