Listeria monocytogenes surface proteins: from genome predictions to function

Abstract

The genome of the human food-borne pathogen Listeria monocytogenes is predicted to encode a high number of surface proteins. This abundance likely reflects the ability of this bacterium to survive in diverse environments, including soil, food, and the human host. This review focuses on the various mechanisms by which listerial proteins are attached at the bacterial surface and their many functions, including peptidoglycan metabolism, protein processing, adhesion to host cells, and invasion of host tissues. Extensive in silico analysis of the domains or motifs present in these mosaic proteins reveals that diverse structural features allow the surface proteome to interact with diverse bacterial or host components. This diversity offers new clues about the molecular bases of Listeria pathogenesis.

FIG. 1.

The different types of surface proteins found in L. monocytogenes. A prototype of each family is given.

FIG. 2.

Sortase substrates. A schematic representation of L. monocytogenes LPXTG and NXXTX proteins is shown. The numbers within domains indicate the number of repeats. Nineteen proteins are absent in L. innocua and are indicated in green letters. Proteins detected in the L. monocytogenes cell wall fraction (146) are indicated by an arrow. The two sortase B substrates, Lmo2185 and Lmo2186, are drawn on the right of LPXTG proteins. AA, amino acids. (Adapted from reference with permission from Elsevier.)

FIG. 3.

Surface proteins predicted to be involved in cell wall metabolism. (A) Schematic representation of L. monocytogenes surface proteins potentially involved in cell wall synthesis, hydrolysis, or modification. AA, amino acids. Most of the enzymatic activities are deduced from domain sequence similarities and require biochemical experimental validation. (B) Cell wall synthetase and hydrolase activities on Listeria peptidoglycan. Glycan chains of GlcNAc and MurNAc are interlinked by direct peptide linkage between the meso-diaminopimelic acid (m-Dpm) residue of one wall peptide and the d-alanyl residue at position 4 of the adjacent wall peptide. A peptidoglycan precursor linked to the undecaprenyl pyrophosphate group (black circle) is represented by a spotted circle. The precursor is incorporated to the preexisting peptidoglycan by the formation of two bonds: (i) a transglycosylase splits the pyrophosphate bond between the undecaprenyl group and the MurNAc of a nascent glycan strand and forms a glycosidic bond between MurNAc and the hydroxyl group of the GlcNAc of the precursor molecule, and (ii) a transpeptidase forms a dd-peptide bond between the carboxyl group of the d-Ala of the precursor and the amino group of an m-Dpm residue present in a peptide moiety of the cell wall. An example of each type of bond attacked by different specific murein hydrolases is also shown. (Adapted from reference with permission.)

FIG. 4.

The two Csc Clusters in L. monocytogenes. The first line shows a characteristic four-component Csc cluster, with the predicted surface-anchoring domain of Csc proteins indicated below. The two L. monocytogenes Csc clusters are schematically represented, with genes corresponding to Csc components indicated in blue (CscA like), yellow (CscB like), green (CscC like), and red (CscD like), respectively. The number of amino acids (AA) in each gene product is indicated. Cluster 2 does not contain any cscD-like gene. PKD, PKD repeats; DUF 919 (Pfam PF06030), domain of unknown function. (Adapted from reference with permission.)

FIG. 5.

Surface proteins predicted to be involved in protein processing, folding, and anchoring at the cell surface. A schematic representation of L. monocytogenes surface proteins potentially involved in modifications or degradation of proteins at the surface is shown. AA, amino acids.