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Measuring Bacterial Load and Immune Responses in Mice Infected with Listeria monocytogenes
Published on: August 9, 2011
Residual Variation Intolerance Score Detects Loci Under Selection in Neuroinvasive Listeria monocytogenes
Bart Ferwerda1, Mylène M Maury2, Mathijs C Brouwer1
1Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Abstract:
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.
Insights
Listeria monocytogenes, a cause of meningitis, was studied for genetic selection in neuroinvasive strains. Researchers identified specific genes under selection, including those involved in metabolism, antimicrobial resistance, and virulence.
Area of Science:
- Microbiology
- Genomics
- Evolutionary Biology
Background:
- Listeria monocytogenes is a Gram-positive bacterium causing sepsis and meningoencephalitis.
- Neuroinvasive strains are a significant public health concern.
- Understanding genetic selection in these strains can reveal virulence mechanisms.
Purpose of the Study:
- To identify loci under selection in the core genome of neuroinvasive Listeria monocytogenes.
- To compare genome-wide analysis methods (Tajima's D, ω (dN/dS), and RVIS) for detecting selection.
- To investigate the functional roles of selected genes.
Main Methods:
- Genome sequencing of 122 L. monocytogenes strains from cerebrospinal fluid (CSF).
- Genome-wide analysis using Tajima's D, ω (dN/dS), and Residual Variation Intolerance Score (RVIS).
- Replication of findings in an external cohort of 105 French CSF isolates.
Main Results:
- Signals of selection were detected in 6 of 2327 loci (<1%) within genetic lineages, replicated in an external cohort.
- Identified loci under selection are involved in metabolism (lmo2476), antimicrobial resistance (lmo1855), and virulence (lmo0549, lmo1482).
- RVIS identified selection signals in internalin-like protein loci (lmo0549, lmo0610, lmo1290) linked to pathogen-host interaction.
Conclusions:
- The genetic distance between listerial lineages impacts Tajima's D and ω (dN/dS) outcomes.
- RVIS is a viable method for detecting bacterial loci under selection, particularly in pathogen-host interaction genes.
- This study provides insights into the evolutionary pressures shaping neuroinvasive Listeria monocytogenes.
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