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LPS Overcoming host resistance Genotype-phenotype maps Experimental evolution ΦX174 E. coli C.

Stepwise evolution of E. coli C and PhiX174 reveals unexpected lipopolysaccharide (LPS) diversity

Abstract ID: 64-AZ

Jordan Romeyer Dherbey 1*, Lavisha Parab 1, Jenna Gallie 2, Frederic Bertels 1

  1. Department Microbial Population Biology, Research Group Microbial Molecular Evolution, Max Planck Institute for Evolutionary Biology, Plön (24306), Germany
  2. Department for Evolutionary Theory, Research Group Microbial Evolutionary Dynamics, Max Planck Institute for Evolutionary Biology, Plön (24306), Germany

Jordan Romeyer Dherbey. email: dherbey@evolbio.mpg.de

Jordan Romeyer Dherbey. Address: Max Planck Institute for Evolutionary Biology, August-Thienemann-Straße 2, 24306 Plön, Germany; email: dherbey@evolbio.mpg.de; phone: + 49 4522 763-278. ORCID 0000-0002-6125-1722.

Phage therapy is a promising method for the treatment of multi-drug resistant bacterial infections. However, its long-term efficacy depends on understanding the evolutionary effects of treatment. Current knowledge of such evolutionary effects is lacking, even in well-studied systems. We use the bacterium Escherichia coli C and its bacteriophage PhiX174, which infects cells using host lipopolysaccharide (LPS) molecules. We generate 31 bacterial mutants resistant to PhiX174 infection and based on the location of resistance mutations and current knowledge, we predict these produce eight distinct LPS structures. Next, we isolate 16 PhiX174 mutants that can, between them, infect all 31 mutant hosts. Finally, we determine the infectivity profiles of the 16 evolved phages, revealing 14 distinct profiles. Given that only eight profiles are expected if LPS predictions hold, our results demonstrate that the current understanding of LPS biology is insufficient to accurately forecast the evolutionary consequences of infecting bacterial populations with phage.