The research group of Clinical Microbiology consists of several independent project groups that work with important human pathogens, both bacteria such as Campylobacter and Chlamydia, and viruses such as retroviruses and Hepatitis C virus. The goals are to understand how these pathogens are spread, how they cause disease, and to improve both detection and treatment as well as preventive measures.
Campylobacter is the most important cause of bacterial gastroenteritis in the western world and causes significant economic and disease burden on society with more than 200 000 reported cases in the EU alone. Campylobacter is a major threat to public health with C. jejuni and C. coli being the major pathogens. Campylobacter is part of the gut flora in many domestic and wild animals and poultry products have often been shown to account for the majority of human infections. Despite the increasing knowledge on molecular epidemiology and ecology as well as the availability of whole genome sequences for Campylobacter, the bacterial pathogenicity mechanisms and human characteristics connected to disease are still poorly understood.
Clinical Microbiology consists of several independent research groups that work with different pathogens, both bacteria such as Campylobacter and Chlamydia, and viruses such as retroviruses and Hepatitis C virus. The goals are to understand how these pathogens are spread, how they cause disease, and to improve both detection and treatment as well as preventive measures.
Detection and analysis of pathogens
Early and rapid detection of disease-causing pathogens is important for combatting infections
caused by bacteria, virus or fungi. As the treatment has to be adopted to the type of pathogen it would be most valuable if common pathogens could be analysed simultaneously in the same sample, so called multiplex testing. We aim therefore to develop diagnostic tests for simultaneous detection of nucleic acids from, and anti-bodies to, viruses, bacteria and fungi. We also work to detect and analyse viral sequences by new bioinformatics methods, and search for pathogens in myalgic encephalomyelitis (chronic fatigue syndrome).
Antiviral treatment and resistance
Hepatitis C virus constitutes a global health problem since it often causes persistent infections with chronic hepatitis that may result in liver cirrhosis and liver cancer. Novel drugs, so called directly acting that target specific viral proteins of the hepatitis C virus, have been developed, but their efficacy can be limited by mutations that render the virus resistance to these drugs.
To better understand resistance mechanisms we investigate the prevalence of natural Hepatitis C virus resistance to protease-NS3 and NS5A inhibitor drugs in untreated patients, analyse resistance mutations by population and ultra-deep sequencing, and conduct a Nordic multicenter study. We also investigate HIV resistance to nucleoside analogs and develop methods to study potential Zika and TBE virus drugs. For more information contact Johan Lennerstrand.
Chlamydia trachomatis is globally the most commonly reported sexually transmitted bacterium and gives rise to complications with infertility as final endpoint. The research group has developed a high-resolution typing system that enables epidemiological investigations of the spread in sexual networks and populations. Epidemiology and prevention of chlamydia from an international public health perspective is also a field of research interest.
Chlamydia psittaci is defined as a high risk pathogen causing fatal respiratory infections, but the spread from wild birds to humans is not well understood. C. psittaci infections in birds and their role for zoonotic disease are investigated. Detection and identification of other bacteria causing respiratory tract infections is an additional research topic.
Several projects are ongoing with the aim to prevent infections. In the Baltic Antibiotic Collaboration Network., the focus is on clinical microbiological diagnostics and surveillance of resistant bacteria, infection prevention and control and antibiotic use. We are, e.g. also taking part in a multi-center study with Lars Engstrand, Professor of Clinical Bacteriology, Karolinska Institute and Gunilla Hamberg, chief physician at the Women's Clinic at the Uppsala University Hospital, where we map the microbial flora in the operating room during cesarean section and its significance for the normal flora of the newly delivered the children.
Campylobacter infections and intestinal microbiota; whole genome sequencing of important bacterial pathogens
Hilpi Rautelin, Cecilia Johansson, René Kaden, Christian Kampmann, Anna Nilsson, Astrid Skarp, Lars Engstrand (KI)
Our research strategy is based on three approaches: to reveal 1) bacterial and 2) human host characteristics relevant for Campylobacter infection and to understand 3) host-pathogen interactions. We apply genome-wide association studies on Campylobacter together with integrated phenotypic characterization to reveal pathogenicity mechanisms of Campylobacter using internationally unique collections of clinically relevant bacterial strains. We also integrate the human gut microbiota in our research and study the role of gut microbiota composition for susceptibility to Campylobacter infection and the impact of Campylobacter infection on gut microbiota composition, along with human host response parameters. We recently showed, for the very first time in humans that, the fecal microbiota composition was associated with susceptibility for Campylobacter infection and that Campylobacter infection had long-term effects on the fecal microbiota composition. Furthermore, individuals whose faecal microbiota had lower diversity became significantly more often infected with Campylobacter than those with a higher diversity of their faecal microbiota composition. In addition, we use in vitro host-pathogen interaction models to study adhesion/invasion mechanisms, cell signaling pathways and downstream effects. Our approach increases understanding of the pathogenicity mechanisms of Campylobacter at a molecular level and helps to direct preventive measures.
Whole genome sequencing is also used to study rare and previously unknown but potentially clinically important bacterial strains. In addition, whole genome sequencing is used to trace contacts in clinical outbreak situations.
Multiplex virus diagnostics, and bioinformatics-led definition of variation tolerant nucleic acid detection and endogenous retroviral sequences
Jonas Blomberg, Christina Öhrmalm, Bengt Rönnberg, Hongyan Xia
We develop nucleic acid and antibody based diagnostic tests which address many viruses at the same time, i.e. multiplex tests. We use these methods for studying zoonotic infections and myalgic encephalomyelitis, the chronic fatigue syndrome. We have unique bioinformatic tools for creation of these tests. Our bioinformatical effort also led to the identification and classification of human endogenous retroviruses.
Chlamydial infections in humans and birds
Björn Herrmann, Hilde Riedel, Jenny Isaksson, Guma Abdeldaim.
Identification of success factors for spread of chlamydia infections
Studies with the genotyping system developed in our group has shown that certain genotypes are predominating in many countries. Ongoing project extend typing to analysis of whole genome sequences and aims to identify factors that lead to the successful spread of infection.
Development of prognostic markers for chlamydia associated infertility
Chlamydia trachomatis cause ectopic pregnancy and infertility. In contrast to most research in this field the current project focus on genetic polymorphism patterns in women. The aim of the project is to develop a diagnostic test that identifies individuals at increased risk for infertility. The project is within the framework of a European consortium.
The spread of Chlamydia psittaci.
Chlamydia psittaci is a high-risk pathogen, but the knowledge about the transmission risk from wild birds to humans is poor. This project investigates the prevalence of C. psittaci in different bird populations and relate it to the risk of transmission to humans. Genetic characterization can elucidate why certain outbreaks have caused high mortality among humans, while most infections appear to cause mild disease.
Antiviral treatment and resistance
Johan Lennerstrand, Assar Bergfors, Midori Kjellin, Dario Akaberi, Adam Ameur, Anders Lannergård, Tore Gutteberg
In collaboration with local and international scientists, our group focuses on the following themes:
1. Study of resistance in Hepatitis C virus prior to treatment with new directly acting antivirals. A Nordic Multicenter Study.2. Ultra deep-sequencing of Hepatitis C virus resistance - in collaboration with SciLifeLab Uppsala. 3. Studying nucleoside analogs candidates against Flaviviruses such as Dengue and TBE. 4. Biochemical mechanism of HIV RT resistance to nucleoside analogs.
Infection Prevention and Control
Birgitta Lytsy, Anna Hambraeus, Ulrika Ransjö
Our group focuses on surveillance of resistant bacteria, infection prevention and control, and antibiotic use. In several projects, local and international collaborators and networks are involved.