Residual Variation Intolerance Score Detects Loci Under Selection in Neuroinvasive Listeria monocytogenes

Bart Ferwerda (1) , Mylène M. Maury (2) , Mathijs C. Brouwer (1) , Lukas Hafner (2) , Arie van Der Ende (1, 3) , Stephen Bentley (4) , Marc Lecuit (2, 5) , Diederik van de Beek (1)

1 Amsterdam UMC - Amsterdam University Medical Center
2 Biologie des Infections - Biology of Infection
3 RIVM - National Institute for Public Health and the Environment [Bilthoven]
4 The Wellcome Trust Sanger Institute [Cambridge]
5 Service des Maladies infectieuses et tropicales [CHU Necker]

Listeria monocytogenes is a Gram-positive bacterium that can be found in a broad range of environments, including soil, food, animals, and humans. L. monocytogenes can cause a foodborne disease manifesting as sepsis and meningo-encephalitis. To evaluate signals of selection within the core genome of neuroinvasive L. monocytogenes strains, we sequenced 122 L. monocytogenes strains from cerebrospinal fluid (CSF) of Dutch meningitis patients and performed a genome-wide analysis using Tajima's D and ω (dN/dS). We also evaluated the residual variation intolerance score (RVIS), a computationally less demanding methodology, to identify loci under selection. Results show that the large genetic distance between the listerial lineages influences the Tajima's D and ω (dN/dS) outcome. Within genetic lineages we detected signals of selection in 6 of 2327 loci (<1%), which were replicated in an external cohort of 105 listerial CSF isolates from France. Functions of identified loci under selection were within metabolism pathways (lmo2476, encoding aldose 1-epimerase), putative antimicrobial resistance mechanisms (lmo1855, encoding PBPD3), and virulence factors (lmo0549, internalin-like protein; lmo1482, encoding comEC). RVIS over the two genetic lineages showed signals of selection in internalin-like proteins loci potentially involved in pathogen-host interaction (lmo0549, lmo0610, and lmo1290). Our results show that RVIS can be used to detect bacterial loci under selection.

Mots clés: Listeria monocytogenes; genetic variation; neuroinvasive; residual variation intolerance score; selection

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie; Maladies infectieuses; Bactériologie; Microbiologie et Parasitologie

Bart Ferwerda, Mylène M. Maury, Mathijs C. Brouwer, Lukas Hafner, Arie van Der Ende, et al.. Residual Variation Intolerance Score Detects Loci Under Selection in Neuroinvasive Listeria monocytogenes. Frontiers in Microbiology, 2019, 10, pp.2702. ⟨10.3389/fmicb.2019.02702⟩. ⟨pasteur-03203104⟩