Comparative Transcriptome Analysis of Listeria monocytogenes Strains of the Two Major Lineages Reveals Differences in Virulence, Cell Wall, and Stress Response

Abstract

Listeria monocytogenes is a food-borne, opportunistic, bacterial pathogen causing a wide spectrum of diseases, including meningitis, septicemia, abortion, and gastroenteritis, in humans and animals. Among the 13 L. monocytogenes serovars described, human listeriosis is mostly associated with strains of serovars 4b, 1/2b, and 1/2a. Within the species L. monocytogenes, three phylogenetic lineages are described. Serovar 1/2a belongs to phylogenetic lineage I, while serovars 4b and 1/2b group in phylogenetic lineage II. To explore the role of gene expression in the adaptation of L. monocytogenes strains of these two major lineages to different environments, as well as in virulence, we performed whole-genome expression profiling of six L. monocytogenes isolates of serovars 4b, 1/2b, and 1/2a of distinct origins, using a newly constructed Listeria multigenome DNA array. Comparison of the global gene expression profiles revealed differences among strains. The expression profiles of two strains having distinct 50% lethal doses, as assessed in the mouse model, were further analyzed. Gene ontology term enrichment analysis of the differentially expressed genes identified differences in protein-, nucleic acid-, carbon metabolism-, and virulence-related gene expression. Comparison of the expression profiles of the core genomes of all strains revealed differences between the two lineages with respect to cell wall synthesis, the stress-related sigma B regulon and virulence-related genes. These findings suggest different patterns of interaction with host cells and the environment, key factors for host colonization and survival in the environment.Listeria monocytogenes is a gram-positive, facultative, intracellular bacterium that causes severe food-borne infections, such as gastroenteritis, septicemia, abortion, and meningitis, in humans and animals (60). L. monocytogenes is able to cross the intestinal barrier, the blood-brain barrier, and the fetoplacental barrier and to invade and replicate inside epithelial and professional phagocytic cells. L. monocytogenes is widely present in nature, and it has also been isolated from numerous animals, including cattle, sheep, and goats (21). Furthermore, L. monocytogenes has the important capacity to adapt to and survive in extreme environments, such as high salt concentration (10% NaCl), a broad pH range (from 4.5 to 9.0), and a wide temperature range. Its ability to grow at temperatures between Ϫ1°C and 45°C increases the risk of contamination in dairy products, meats, seafood, and other processed food products via selective enrichment during refrigeration. Listeria can also survive long periods of drying and freezing with subsequent thawing (38, 54). L. monocytogenes is an environmental bacterium living, for example, on decomposing plants. However, the presence of virulence factors, which have most probably been acquired by a common ancestor through horizontal gene transfer (for reviews see references 7 and 56), allows L. monocytogenes to infect humans and other mammalian hosts. Most ...

Listeria monocytogenes σ B Has a Small Core Regulon and a Conserved Role in Virulence but Makes Differential Contributions to Stress Tolerance across a Diverse Collection of Strains

“…Information about the contributions of B to regulation of gene expression in strains belonging to lineages I, IIIA, and IIIB is just emerging. A recent comparative transcriptomic study found that sigB (lmo0895) was expressed at higher levels in lineage II strains than in lineage I strains (53). Also, a number of previously identified B -regulated genes (30,48) were expressed at higher levels in lineage II strains than in lineage I strains; these genes include opuCA and lmo1421, which encode a known compatible solute transporter protein and a putative compatible solute transporter protein, respectively.…”

“…The contributions of B to L. monocytogenes stress responses and virulence have been characterized most thoroughly for lineage II strains, including strains 10403S (44,48) and EGD-e (21,53). For example, the relative virulence characteristics of the lineage II strain 10403S and its isogenic ⌬sigB mutant have been evaluated in the guinea pig model, but contributions of B to gastrointestinal infection have not been reported for other L. monocytogenes lineages.…”

“…The third lineage, lineage III, can be subdivided into lineages IIIA/C and IIIB (lineage IIIB has recently been classified as lineage IV [65]), based on results obtained with a number of molecular subtyping strategies, including pulsed-field gel electrophoresis (PFGE) (20) and virulence gene sequencing (20,68). While different nomenclatures have been used for these L. monocytogenes lineages (47,53), the main groups described in multiple studies consistently include the same L. monocytogenes serotypes (20,53,66,68). Based on the most commonly applied lineage designations (20), lineage I includes predominantly strains with the 1/2b, 3b, 3c, and 4b serotypes and lineage II includes primarily strains with the 1/2a, 1/2c, and 3a serotypes (38).…”

Ruminant Rhombencephalitis-Associated Listeria monocytogenes Alleles Linked to a Multilocus Variable-Number Tandem-Repeat Analysis Complex

“…The second objective was to determine whether polymorphisms of virulence genes are associated with a putative MLVA cluster or origin of the isolate. A wide variety of virulence genes are involved in the intracellular life cycle of L. monocytogenes within the host (11,12,15,17,54,60). These include Listeria pathogenicity island 1 (LIPI-1), which contains six key virulence genes (i.e., prfA, plcA, hly, mpl, actA, and plcB) (26,31,40,60), and various internalin genes scattered over the L. monocytogenes genome (18,19,51,52).…”

Transcriptomic and Phenotypic Responses of Listeria monocytogenes Strains Possessing Different Growth Efficiencies under Acidic Conditions

“…Strain diversity within L. monocytogenes may affect phenotypic characteristics, for example, virulence (57), and may lead to variants with different levels of resistance to and tolerance of different forms of stress (56,62). These differences may affect the incidence of the strains in the environment, including the food supply chain (39), and their presence in human clinical samples (23).…”