FINISHED PROJECTS

Antimicrobial resistance (AMR) is becoming an increasingly urgent concern in our world. As more and more microbes develop resistance to antimicrobials, infectious diseases which were commonly able to be treated, become more difficult to deal with. As part of Interdisciplinary Project Team 2 (IPT2) we are primarily focused on microbes which may cause infections of the lung and are well known to develop resistance to antimicrobials. These infections do not usually occur in healthy people, but can occur in those having problems with the immune system or those who suffer from lung conditions, such as cystic fibrosis. Often these microbes do not cause infections alone, but form highly-structured polymicrobial communities, known as “biofilms”. In view of high cell densities and species diversity, it is not surprising that physical and social interactions within mixed biofilms may lead to cooperation or competition between the cells, which in turn may result in remodelling or even evolution of the members of the biofilm community, including the development of antimicrobial resistance to name just one possible outcome of microbial evolution. It is therefore extremely important to understand how the microorganisms evolve and adapt to new environments in mixed biofilm-forming consortia, given the rapid development of antimicrobial resistance and the consequences for the treatment of infectious diseases. Within the framework of the current project we intend to examine the interactions between pulmonary opportunists and arising antimicrobial resistance in mixed biofilms, placing a special focus on bacterial and fungal pathogens affecting cystic fibrosis patients, such as Stenotrophomonas maltophilia and Candida albicans. In order to mimic the conditions of the human respiratory system and achieve the complexity of the in vivo situation in an in vitro model, we will investigate the biofilm communities in physiologically relevant cell culture systems at the air-liquid interface.

Participating Institutes: FZB, HKI, DPZ, DSMZ, LIV, IPHT, ISAS

The rising use of antibiotics in health and agriculture are driving the increase in antimicrobial resistance (AMR). The increasing use of antibiotics in the health- and livestock sectors along with ineffective stewardship have already led to alarming rates of antimicrobial resistant pathogens – a situation with severe consequences for society. Experts estimate that by 2050 ten million people will die each year from common infections that will then be no longer treatable. The central objective of this research project is to support optimal patterns of antibiotic use worldwide. The focus of this project is on two areas in particular: One, reducing the excessive use of antibiotics and two, promoting equal access to quality antibiotics. The excessive use of antibiotics stems from two sources: A lack of stewardship, standards and controls of medicines, and a lack of diagnostic tools that allow distinguishing between bacterial and viral infections – an information essential for treatment that is effective. Hence, this project will assess the role of better diagnostic tools, more information and transparency for curbing antimicrobial resistance. It will assess the cost-effectiveness of a variety of measures and interventions at the micro- and the macro level and provide concrete policy recommendations.

Participating Institutes: BNITM, GIGA, FZB, IfW, RWI

The project focuses on vector ecology. Vectors like filth flies are able to transport and disseminate various pathogens including bacteria, fungi, viruses and parasites. The common house fly (Musca domestica) can transport bacteria over distances of 5-7 km. It breeds in and feeds on decaying organic matter and animal feces. Due to this coprophagic behaviour bacteria may be ingested and can later be transmitted onto human food by regurgitation and defecation. The frequent preventive use of antibiotics on farms and in lifestock production leads to the emergence of antimicrobial resistant bacteria. These can be disseminated by flies from farm environments to urbanized areas causing severe nosocomial infections among citizens. To understand the potential of flies to spread bacteria over different landscape types and from farm environments to urbanized areas, a mark-release-recapture experiment will be conducted. For this purpose, adults of M. domestica are captured, marked by different colours with a permanent dye and released again. The recapture rate will be determined using specialized dipteran traps. The results will help understand the flight range and the habitat binding of the muscid. Strategies to prevent and inhibit the spread of antimicrobial-resistant bacteria by flies will be elucidated. In a further step, the persistence and multiplication of these bacteria in the flies will be investigated under a laboratory setting. The three larval stages of the muscid fly develop in manure and animal feces where they may ingest antimicrobial resistant bacteria excreted by the lifestock animals. Of special intrest is if the ingested bacteria survive the metamorphosis. This indicates that they can remain in the puparium after histolysis or persist in the newly emerged imagos. Altogether, this project will help understand how antimicrobial resistant bacteria survive and persist during the life cycle of flies and how adult flies transport and disseminate them to urbanized areas.

Participating Institutes: ZALF, DSMZ, ATB, IOER

Within Interdisciplinary Project Team 5 (IPT5) the ATB and partners work intensively together to determine the mechanisms of antimicrobial resistance (AMR) transmission in animal husbandry and to evaluate possible intervention measures. We compare AMR occurrence in typical conventionally grown pigs in a standard and improved hygienic environment (by using insecticides, flytraps, increased disinfection and dusting). In addition, the antibacterial activities of different feed additives will be compared to the basic diet based on microbial colonization in the gut of piglets during the early fattening period. In close cooperation with other INFECTIONS partners, the survival and propagation of AMR microbes in pig faeces, dust and flies under all conditions will be analyzed. The abundance of AMR based on bacteriological methods, PCR and cultivation-independent DNA sequencing will be conducted. With support from other IPTs, the findings will guide interventions and potential mitigation strategies to minimize AMR spread in commercial animal husbandry to reduce potential contamination of the environment (e.g. surface water, when the slurry is used as organic fertilizer on agricultural fields).

Participating Institutes: ATB, DSMZ, ZALF, HKI, IPHT, IOER, VRC²

Antimicrobial resistance (AMR) has been declared by the World Health Organization (WHO) as one of the top 10 global public health threats in the presence and near future. According to WHO, AMR will have a disastrous impact within a generation unless an urgent and effective global mitigation plan is finally implemented. In a recent study, data from 204 countries suggest a burden of 1,27 million deaths associated with AMR bacteria in 2019. One of the challenges of monitoring AMR organisms and antimicrobial resistance genes (ARGs) is their ubiquitous distribution, i.e. they are generally found in humans, animals, plants, microbes and the environment like water, soil and air. In particular, water plays a key role as a vector and reservoir for AMR transmission across urban and rural areas. Our preliminary results suggest that the abundance of AMR in urban waters and sediments is substantially higher compared to rural water bodies. In addition, rural lakes sediments and water derived from farmlands is observed to be a major source of environmental AMR due to frequent antibiotics use for cattle raising. The approach defined for Interdisciplinary Project Team 6 (IPT6) seeks to provide further understanding on AMR dispersion from WWTPs to the environment as well as to characterize the humanization of urban water microbiomes. In particular, the use of long-read sequencing in this project will allow to recover mobile genetic elements (MGEs) such as plasmids and genomic islands (GIs) and thus a higher resolution in the metagenome assembly. Also, risk assessment will be performed in order to evaluate the environmental exposure to ARGs. The results from this project will allow to directly link frequency and diversity of AMR and the carrying bacteria to other findings and team up with institutions of the Leibniz Research Alliance (LRA) INFECTIONS, providing a broad overview of AMR profiles in different waters and potential disease vectors of concern in the area of Berlin-Brandenburg.

Participating Institutes: IZW, IGB, LIV, DPZ, GIGA, IOER

Characterisation of aerosols that can transmit pathogens via the air

Respiratory pathogens, such as tuberculosis bacteria or influenza A viruses can be transmitted to humans in different ways: Through direct contact with an infected person, by touching contaminated surfaces or by inhaling the pathogens through the air. Until now, very little is known about how pathogens are transported through the air and how the aerosols that transport these pathogens are structured. Aerosols are suspensions consisting of solid or liquid particles that can float in the air over a long period of time. They therefore represent an optimal means of transport for the pathogen to be transmitted via the air.
The air research project aimed to shed more light on this transmission path and to model the transport path of aerosols in the air. To this end, the biophysical properties of the pathogens, which have a major influence on how they are transported through the air, were first investigated. Besides size, surface properties and morphology, hygroscopicity also played an important role. This refers to the ability to absorb and bind water from the air. Following these investigations, aerosols from the ambient air and from the respiratory tract of infected hosts were detected and characterised. These findings can help to identify infection risks and establish protective measures.

Project participants:
Trainee: Elisabeth Pfrommer
Supervision: K. Schepanski (TROPOS), G. Gabriel (HPI), T. Gutsmann (FZB),
U.E. Schaible (FZB)
Partner: ATB, FLI, FZB, GESIS, GIGA, HPI, PIK

Waters as a reservoir for pathogens

Water is a vital element for all living things. At the same time, it is also a habitat for a multitude of microorganisms, including pathogens that can be transmitted to humans or animals via water. Ponds, rivers and lakes can therefore represent a central reservoir for pathogens. The pathogens enter the water body via sewage, animals and humans, from where they can infect other individuals and thus spread. Especially water bodies of small size can serve as a hotspot, as they are usually rich in nutrients and are a meeting point for a large number of water birds. Furthermore, small water bodies are a preferred habitat for the offspring of bloodsucking insect species.
The aim of the research project was to investigate the occurrence of pathogens such as Clostridium difficile and (avian) influenza A viruses. Various water sources in the Berlin area were selected for these investigations, including five lakes, the Berlin Zoo and a sewage treatment plant. To be able to observe seasonal changes, the sites were sampled every three months. In addition to water, sediment samples were taken from the lakes and environmental parameters such as temperature, pH value and nutrient concentrations were documented. In addition, molecular genetic methods were used to record the microbiome, i.e. the entire bacterial community of a site.

Project Participants:
Trainee: Daniela Numberger
Supervision: A. Greenwood (IZW), H.-P. Grossart (IGB)
Partner: DSMZ, HPI, IGB, IZW, ZALF, ZMT

Vectors as potential carriers of pathogens

Vectors are living organisms that transmit pathogens from an infected animal or human to other humans or animals. Among the most important vectors are arthropods, as well as rodents, such as the bank vole. These can transmit diseases such as malaria, borreliosis or the hantavirus. Especially the mosquito as a potential vector has become more and more important in recent years, as could be seen from the recent Zika virus epidemic in South and Central America. Globalisation and global warming have for some time been contributing to the spread of vectors and the increasing availability of sources of infection. Native bloodsuckers can therefore encounter new pathogens and new vectors can become carriers of introduced pathogens. At present, however, there is insufficient knowledge of the ecology and vector competence of native species for appropriate risk analyses. This is where the work of the vector group should make a contribution. Breeding habitats were investigated, host preferences analysed and collected mosquitoes tested for pathogens. Zoological gardens are ideal study areas for such investigations, as the animals kept there are closely monitored and diseases are thus quickly detected. In addition, wild animals such as migratory birds live here, which can introduce pathogens. Competent vectors would thus make it possible to transmit pathogens from the wild reservoir to zoo animals.

Project Participants:
Trainee: Eva Heym
Supervision: H. Kampen (FLI), D. Walther (ZALF)
Partner: BNITM, FLI, IGB, IZW, PIK, ZALF