Spontaneous virulence loss in natural populations of Listeria monocytogenes

Mylène M. Maury, Viviane Chenal-Francisque, Hélène Bracq-Dieye, Lei han, Alexandre Leclercq, Guillaume Vales, Alexandra Moura, E Gouin, Mariela Scortti, Olivier Disson, Jose Vazquez-Boland, Marc Lecuit

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Listeria monocytogenes (Lm) pathogenesis depends on its ability to escape from the phagosome of the host cells via the action of the pore-forming toxin listeriolysin O (LLO). Expression of the LLO-encoding gene (hly) requires the transcriptional activator PrfA, and both hly and prfA genes are essential for Lm virulence. Here we used the hemolytic activity of LLO as a phenotypic marker to screen for spontaneous virulence-attenuating mutations in Lm. Sixty (0.1%) non-hemolytic isolates were identified among a collection of 57,820 confirmed Lm strains isolated from a variety of sources. In most cases (56/60), the non-haemolytic phenotype resulted from nonsense, missense or frameshift mutations in prfA. Five strains carried hly mutations leading to a single amino acid substitution (G299V) or a premature stop codon causing strong virulence attenuation in mice. In one strain, both hly and gshF (encoding a glutathione synthase required for full PrfA activity) were missing due to genomic rearrangements likely caused by a transposable element. The PrfA/LLO loss-of-function mutants belonged to phylogenetically diverse clades of Lm and most were identified among non-clinical strains (57/60). In line with the extremely low frequency of loss of virulence mutations, we show that prfA and hly are under purifying selection. Although occurring at a low frequency, PrfA–/LLO– mutational events in Lm lead to niche restriction and open an evolutionary path for obligate saprophytism in this facultative intracellular pathogen.
Original languageEnglish
JournalInfection and Immunity
Publication statusPublished - 21 Aug 2017

Keywords / Materials (for Non-textual outputs)

  • Listeria monocytogenes
  • virulence
  • hemolysis


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