Microbiome context-dependence in the evolution of antibiotic resistant Klebsiella pneumoniae

Michael Knopp

EMBL Heidelberg, Genome Biology, Meyerhofstr. 1, 69117 Heidelberg [DE], knopp@embl.de

Author(s): Michael Knopp, Sarela Santamarina, Denise Selegato, Vitor Cabral, Lina Michael, Nicolai Karcher, Joshua Wong, Michael Zimmermann, Karina Xavier, Nassos Typas

Antibiotic resistance (AR) can impose a fitness cost to the bacterium. Identifying conditions that enhance this cost offers a way to counter-select AR populations. Typically, fitness is assessed in monocultures under artificial conditions, which are far from the complex natural habitats of enteric pathogens. To determine the influence of the microbiome composition on the fitness of AR bacteria, we established a highly sensitive method to determine fitness in complex communities using flow cytometry. We identified a microbiome-specific selection of a carbapenem-resistant K. pneumoniae strain mediated by the acquisition of a secondary mutation in the transcriptional repressor cscR causing upregulation of a carbohydrate-catabolic operon. The selective advantage was largely due to a specific focal E. coli strain, it is contact independent, not-transferable to other microbiomes, the effect size can be modulated by further competitors and it is driven by differential carbohydrate preferences. We are currently applying our findings to an in vivo mouse model to show that nutrient availability shaped by microbiome specific factors can play an important role in competitiveness of AR subpopulations. Our results highlight the microbiome as an overlooked factor when characterizing the fitness of AR-mutants, which could potentially be exploited to minimize the reservoir of AR pathogens in the human gastrointestinal tract.

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