MiFactR—Microbiota- and treatment-derived determinants of antibiotic resistance
There are a number of factors responsible for the development of antibiotic resistance. So far, the interactions between pathogens and the complex microbial colonisation (microbiota) of the human body under the selection pressure of antibiotic treatment play a little studied and underestimated role. DZIF-coordinated study cohorts such as TIARA make it possible to investigate this topic more closely along the intestinal-lung-kidney axis in patients undergoing antibiotic treatment in the context of surgical interventions. To do this, the researchers are examining patients as the treatment progresses to better understand the impact of anti-infective strategies on microbiota, isolate the variety of microbes present in those patients by high-throughput cultivation assays (culturomics) and use gathered information and isolated microorganisms to model and understand how complex microbial consortia contribute to development and spread of antimicrobial resistance.
View into a laboratory of the MiFactR project: working at the anaerobic workplace is part of everyday project routines.
The microbiota is playing a dual role in the development of antibiotic resistance. On the one hand, a “healthy” microbiota can diminish the need of antibiotic therapy by preventing infection. On the other hand, antibiotic treatment can lead to drastic shifts within the microbiota and such a modified microbiota might give space to growth of multi-resistant pathogens and/or change the mechanistics and kinetics of spread of antibiotic resistance. Therefore, MiFacR integrates the microbiota as an important variable in determining the functional background of resistance development.
In order to identify the impact of antibiotic treatment regimes on the microbiota the microbial instability within patients under antibiotic therapy are analysed. Advanced sequencing techniques are used to study the diversity and functions of microorganisms in the patient's body.
In parallel, extensive cultivation procedures are carried out in the microbiology laboratory to characterise individual microbial species more precisely. By analysing the entire genome of these isolates, detailed insights into their genetic properties become possible. At the same time, comparative studies can be carried out between different strains derived from the same or different samples.
„By using sub-inhibitory concentrations of antibiotics as a stress factor, we can experimentally investigate the development of antibiotic resistance in microbial consortia. In this way, we gain valuable knowledge about the mechanisms of microbial communities that contribute to the development of antibiotic resistance.“
Experiments are currently being conducted with different bacterial consortia to investigate the effects of different microbiota on the development of resistance patterns. In addition to the experiments, various omics technologies such as RNA sequencing and proteomics/metabolomics analyses are used to identify significant molecular patterns. The data obtained will lead to an improved understanding of the role of the microbiome in the emergence and spread of antibiotic resistance. This in turn will allow strategies to be developed to reduce the negative impact of antibiotic therapy on target organisms.
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