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  • Review Article
  • Published:

Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens

Nature Reviews Microbiology volume 8, pages 171–184 (2010)Cite this article

Subjects

Key Points

  • The interaction of probiotic surface molecules with host pattern recognition receptors (PRRs) and associated co-receptors plays a key part in the observed health benefits of probiotic bacteria.

  • Flagella, fimbriae, secreted proteins, cell wall-associated polysaccharides (CPSs), lipoteichoic acid (LTA), lipopolysaccharide (LPS) and peptidoglycan (PG) are important probiotic surface molecules that contain microorganism-associated molecular patterns (MAMPs), which are recognized by PRRs.

  • Documented PRRs that can transduce signals on interaction with probiotic surface molecules include Toll-like receptor 2 (TLR2) (in heterodimers with TLR1 or TLR6), TLR4 and TLR5, the C type lectin dentritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and nucleotide-binding oligomerization domain-containing protein (NOD)-like receptors. These receptors do not function in isolation but cooperate with various co-receptors.

  • PRRs transduce these signals, through associated adaptor proteins that are linked to nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signalling cascades, to the cell nucleus to modulate the expression of response genes that include genes for cytokines, chemokines, antimicrobial peptides, cytoprotective factors and co-stimulatory molecules.

  • Non-phagocytic intestinal epithelial cells and phagocytic DCs differ in their responsiveness for probiotic MAMPs. This is especially relevant for LTA, LPS and PG, as their MAMPs are normally embedded in the cell walls of whole bacterial cells.

  • Some parallels can be drawn between the interactions of the isolated surface molecules of probiotics, commensals and pathogens. However, it is the coordinated sum of the interactions of the various bacterial surface and effector molecules with the PRRs and co-receptors that determines the final host cell response against a certain microorganism.

  • Surface molecules of probiotic bacteria and their host receptors are subject to dynamic regulation as a function of time and space. Glycans are important in these dynamics, possibly modulating ligand–receptor interactions and providing an additional opportunity of discrimination between MAMPs of probiotics, commensals and pathogens.

Abstract

How can probiotic bacteria transduce their health benefits to the host? Bacterial cell surface macromolecules are key factors in this beneficial microorganism–host crosstalk, as they can interact with host pattern recognition receptors (PRRs) of the gastrointestinal mucosa. In this Review, we highlight the documented signalling interactions of the surface molecules of probiotic bacteria (such as long surface appendages, polysaccharides and lipoteichoic acids) with PRRs. Research on host–probiotic interactions can benefit from well-documented host–microorganism studies that span the spectrum from pathogenicity to mutualism. Distinctions and parallels are therefore drawn with the interactions of similar molecules that are presented by gastrointestinal commensals and pathogens.

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Figure 1: The probiotic Gram-positive and Gram-negative surface macromolecules and glycobiome.
Figure 2: Interaction of probiotic bacteria with IECs and DCs from the GALT.
Figure 3: Probiotic MAMP–PRR interactions in IECs and associated signalling events.
Figure 4: Probiotic MAMP–PRR interactions in DCs and associated signalling events.

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Acknowledgements

We apologize to those colleagues whose work had to be omitted through considerations of space. S.L. holds a BOF postdoctoral Mandate from the Katholieke Universiteit Leuven, Belgium. S.C.J.D.K. was a postdoctoral research fellow of the Research Foundation Flanders (FWO-Vlaanderen). We are also grateful for the financial support of FWO-Vlaanderen (project G.0236.07). We thank W. de Vos for exchange of information and interesting discussions.

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Authors and Affiliations

  1. Centre of Microbial and Plant Genetics, K.U.Leuven, Kasteelpark Arenberg 20, bus 2460, Leuven, B-3001, Belgium

    Sarah Lebeer, Jos Vanderleyden & Sigrid C. J. De Keersmaecker

  2. Institute for Nanoscale Physics and Chemistry (INPAC), K.U.Leuven, Celestijnenlaan 200D, Leuven, B-3001, Belgium

    Jos Vanderleyden

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DATABASES

Entrez Genome Project

Bacteroides fragilis

Bacteroides thetaiotaomicron

Escherichia coli

Helicobacter pylori

Lactobacillus acidophillus NCFM

Lactobacillus plantarum WCFS1

Lactobacillus rhamnosus GG

Lactobacillus salivarius

Salmonella enterica subsp. enterica serovar Typhi

Salmonella enterica subsp. enterica serovar Typhimurium

Staphylococcus aureus

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Glossary

Mutualism

An interaction between two species such that both partners benefit in some way. For example, the gut microbiota receives nutrients from the host and provide the host with additional genetic and metabolic attributes, including the ability to harness nutrients that are otherwise inaccessible.

Adjuvant

Any substance that acts to accelerate, prolong or enhance antigen-specific immune responses when used in combination with specific vaccine antigens.

Defensin

In mammals, defensins are one of the major families of antimicrobial peptides that have a key role in the protection of mucosal surfaces against microbial invasion. They are usually 30–42 amino acids long, have a cationic charge and contain six cysteine residues that participate in three intramolecular disulphide bonds. Most defensins function by binding to the microbial cell membrane, resulting in the formation of pore-like membrane defects.

Tight junctions

Lipid–protein complexes at the apical junctions of epithelial cells, forming a barrier that can selectively allow the passage of ions and electrolytes.

Membrane lipid rafts

Transient cholesterol- and sphingolipid-enriched microdomains found in eukaryotic cell membranes, compartmentalizing cellular processes. They serve as organizing centres for the assembly of signalling molecules and receptors, for example.

Moonlighting protein

A protein that has more than one role in an organism. Well-known examples in bacteria are cytosolic glycolytic enzymes, such as glyceraldehyde 3-phosphate dehydrogenase and enolase, which can function as adhesins once secreted outside the cell.

Prohibitin

A putative tumour suppressor molecule that regulates the mammalian cell cycle. Prohibitin and its related members are abundant in mitochondria but are also present in the cell membrane and the nucleus. In intestinal epithelial cells, prohibitin-like proteins are enriched in lipid rafts and are believed to be involved in signalling events.

Phase variation

The (epi)genetic reversible on-and-off switching of surface epitope production that may function to provide a pool of bacteria with an evolutionary advantage upon rapid environmental changes.

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Lebeer, S., Vanderleyden, J. & De Keersmaecker, S. Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat Rev Microbiol 8, 171–184 (2010). https://doi.org/10.1038/nrmicro2297

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