Residual Variation Intolerance Score Detects Loci Under Selection in Neuroinvasive .

is a Gram-positive bacterium that can be found in a broad range of environments, including soil, food, animals, and humans. can cause a foodborne disease manifesting as sepsis and meningo-encephalitis. To evaluate signals of selection within the core genome of neuroinvasive strains, we sequenced 122 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 (, encoding aldose 1-epimerase), putative antimicrobial resistance mechanisms (, encoding PBPD3), and virulence factors (, internalin-like protein; , encoding comEC). RVIS over the two genetic lineages showed signals of selection in internalin-like proteins loci potentially involved in pathogen-host interaction (, , and ). Our results show that RVIS can be used to detect bacterial loci under selection.