Bacterial Evolution Associated with Infections in Humans
Microbial infections in humans are causing increasing global problems due to a number of factors - increased traveling activity, large scale industrial food production, reduced development of immune tolerance as a consequence of modern life-style, and last but not least due to the rapid spread of antibiotic resistance in the microbial populations. The research projects within the area of Infection Microbiology rest on a multidisciplinary platform of methods from molecular microbiology, bioinformatics and nano-technology. The research aims at an improved understanding of bacterial infection processes and the parallel development of tolerance to the host defense systems and anti-microbial interventions. The research program is based on the general assumption that most/all long-term microbial infections can most productively be characterized from an ecological/evolutionary perspective.
The major questions we ask are:
- How do bacteria establish an infection initially?
- Which mechanisms do they employ to resist the host defense and antibiotic treatments?
- How do they adapt and evolve to persist as chronic infections?
Together with other DTU microbiologists and clinical microbiologists in the Copenhagen area we will create a platform the focused aim of which is to establish a bacterial infection data base through systematic accumulation of global data sets concerning epidemiology, genomics and metagenomics, transcriptomics, proteomics, metabolomics, population structures and diversity, as well as adaptative and evolutionary processes. We will design a range of experimental models from animals to lab-on-a-chip devices based on micro-fluidics in collaboration with national and international partners which offer reliable and operational infection simulations from which relevant data can be extracted, and which may later be employed in tests of intervention strategies. It is a final aim to exploit this data base in connection with development of a network of models with predictive powers in collaboration with CBS, DTU mathematicians and physicists, and other partners.
The research projects currently worked on are:
- Bacterial infections in human airways (cystic fibrosis patients)
Development of resistance in microbial populations
Design and experimentation in multi-chamber flow system biofilms
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Bacterial infections in human airways (cystic fibrosis patients)
(Søren Molin)
The ability to establish life-long persistent infections is a fundamental aspect of the interactions between many pathogenic microorganisms and their mammalian hosts. One example is the evolution of chronic lung infections by the opportunistic pathogen Pseudomonas aeruginosa in patients with the hereditary disease cystic fibrosis. The development of chronic infections is associated with extensive genetic adaptation and micro-evolution of the infecting bacteria which result in phenotypes of which many are not usually observed among environmental isolates. We have an expanding collection of isolates that we examine with advanced methods.
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Evolution of complex antibiotic resistance mechanisms
(Anders Folkesson)
We want to understand how complex antibiotic resistance mechanisms evolve and how the consequences of resistance mutation affect the whole biology of infectious bacteria.
The ultimate goal of our research is by combining system level analysis of the host-microbe interaction with experimental microbial evolution; develop novel interventions that can influence the evolution of the host microbe interaction in direction that enables the host to control or clear the infection.
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Persistent P. aeruginosa infections in animals and humans
(Lars Jelsbak)
P. aeruginosa is an opportunistic pathogen that causes a range of acute diseases in both humans and animals. In certain cases, such as in the airways of human cystic fibrosis (CF) patients and in the canine ear, P. aeruginosa may establish long, chronic infections. The infection process of the CF airways is associated with extensive genetic adaptation and evolution of the infecting P. aeruginosa bacteria over time. The accumulation of mutations results in strains with phenotypes of which many are not usually observed among environmental isolates. The occurrence of a range of genetic variants during chronic infections of the CF airways suggests within-host, parallel evolution of the infecting bacteria that secures their persistence and long-term survival.
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System-independent properties of persistent bacterial-host interactions
(Lars Jelsbak)
We have recently shown that P. aeruginosa strains isolated from both from human and chronic canine ear infections exhibit phenotypes that are often associated with strains from CF patients. The finding of shared, system-independent phenotypes raises the possibility that the evolutionary pathways (or parts of them) that lead to a successful chronic colonizer may be parallel in different hosts and niches.
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In situ evolution of successful persistent colonizer of CF airways
(Lars Jelsbak)
We are systematically analyzing a particular cell line that has adapted to the CF airways. This is a remarkable model system for studies of niche adaptation, genome evolution and to explore the basic rules of biological evolution. Using genome-wide analytical tools such as transcriptomic analysis and whole-genome sequencing, we are in the process of outlining the adaptive changes that occurred.
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Other projects
• Bacterial Evolution During Long-term Infections in Cystic Fibrosis Lungs
• Simulation of the Cystic Fibrosis patient airway habitats using microfluidic devices
• Colonization of the human stomach by Helicobacter pylori