Acinetobacter baumannii: genomic profiling of an emerging hospital pathogen
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
Acinetobacter baumannii is a bacterium that causes infections in critically ill patients in hospital. It has an alarming propensity to cause hospital outbreaks and a worrying ability to acquire resistance to multiple antibiotics. Acinetobacter infection has also emerged as a particular threat to returning casualties of the Iraq and Afghanistan wars. Serious gaps remain in our knowledge as to how this organism spreads, causes disease and resists antibiotics. In this proposal, we have assembled an inter-disciplinary team of researchers from the University of Birmingham, the National Health Service and the Health Protection Agency to exploit a new cutting-edge approach (high-throughput bacterial genome sequencing) to fill these gaps and advance our understanding of multi-drug resistant Acinetobacter baumannii.
Technical Summary
Acinetobacter baumannii is an important cause of healthcare-associated infection, with an alarming propensity to cause hospital outbreaks and worrying ability to acquire resistance to multiple antibiotics. This organism is superbly well adapted for survival and transmission within the hospital environment and has proven a problem in hospitals across the developed world. Acinetobacter infection has also emerged as a particular threat to returning casualties of the Iraq and Afghanistan wars.
Molecular typing approaches pioneered by Jane Turton in the Health Protection Agency have provided clear evidence of outbreaks within UK hospitals, with indistinguishable isolates affecting multiple patients within a short space of time. Within Birmingham, A. baumannii has proven a recurrent problem for several years, with serial or overlapping outbreaks caused by several distinct multi-drug resistant strains.
In this proposal, we aim to use high-throughput bacterial genome sequencing to advance our understanding of the biology, epidemiology and evolution of multi-drug resistant Acinetobacter baumannii and to explore the potential of genome sequencing as a tool in clinical microbiology and infection control. In pursuit of these goals, we will draw upon:
? an inter-disciplinary team of researchers from the academic sector, the NHS and HPA
? cutting-edge sequencing technology
? privileged access to the Centre for Infections? unique strain collection and data.
We anticipate that this project will pioneer approaches that could be applied to a wide range of human pathogens and will facilitate the adoption of high-throughput bacterial genome sequencing throughout public health organisations across the world.
Our objectives are to
1. To explore the genomic epidemiology and genetic determinants of virulence and resistance in globally important lineages of MDR Acinetobacter baumannii, focusing on epidemic strains of national and local importance.
2. To define the pan-genome (core genome and flexible gene pool) and species boundaries of Acinetobacter baumannii by genome sequencing diverse strains from this species together with representatives of related taxa.
3. To exploit genome sequencing as an epidemiological tool to resolve fine-grained differences between isolates indistinguishable by established methods, focusing on epidemiologically related isolates from local outbreaks and on genetically related isolates from multiple locations.
4. To optimise sample preparation and sequencing workflows for work with fresh minimally passaged clinical isolates.
5. To make genome sequence data more easily interpretable by laboratory and clinical staff, defining pathogen genome profiles in terms of antibiotic resistance and virulence.
6. To appraise the impact of rapid bacterial genome sequencing, performed prospectively, in diagnosing, understanding and controlling hospital infection.
Molecular typing approaches pioneered by Jane Turton in the Health Protection Agency have provided clear evidence of outbreaks within UK hospitals, with indistinguishable isolates affecting multiple patients within a short space of time. Within Birmingham, A. baumannii has proven a recurrent problem for several years, with serial or overlapping outbreaks caused by several distinct multi-drug resistant strains.
In this proposal, we aim to use high-throughput bacterial genome sequencing to advance our understanding of the biology, epidemiology and evolution of multi-drug resistant Acinetobacter baumannii and to explore the potential of genome sequencing as a tool in clinical microbiology and infection control. In pursuit of these goals, we will draw upon:
? an inter-disciplinary team of researchers from the academic sector, the NHS and HPA
? cutting-edge sequencing technology
? privileged access to the Centre for Infections? unique strain collection and data.
We anticipate that this project will pioneer approaches that could be applied to a wide range of human pathogens and will facilitate the adoption of high-throughput bacterial genome sequencing throughout public health organisations across the world.
Our objectives are to
1. To explore the genomic epidemiology and genetic determinants of virulence and resistance in globally important lineages of MDR Acinetobacter baumannii, focusing on epidemic strains of national and local importance.
2. To define the pan-genome (core genome and flexible gene pool) and species boundaries of Acinetobacter baumannii by genome sequencing diverse strains from this species together with representatives of related taxa.
3. To exploit genome sequencing as an epidemiological tool to resolve fine-grained differences between isolates indistinguishable by established methods, focusing on epidemiologically related isolates from local outbreaks and on genetically related isolates from multiple locations.
4. To optimise sample preparation and sequencing workflows for work with fresh minimally passaged clinical isolates.
5. To make genome sequence data more easily interpretable by laboratory and clinical staff, defining pathogen genome profiles in terms of antibiotic resistance and virulence.
6. To appraise the impact of rapid bacterial genome sequencing, performed prospectively, in diagnosing, understanding and controlling hospital infection.
