Phenotypical analysis of the Lactobacillus rhamnosus GG fimbrial spaFED operon: surface expression and functional characterization of recombinant SpaFED pili in Lactococcus lactis

PLoS One. 2014 Nov 21;9(11):e113922. doi: 10.1371/journal.pone.0113922. eCollection 2014.

Abstract

A noticeable genomic feature of many piliated Gram-positive bacterial species is the presence of more than one pilus-encoding operon. Paradigmatically, the gut-adapted Lactobacillus rhamnosus GG strain contains two different fimbrial operons in its genome. However, whereas one of these operons (called spaCBA) is encoding for the functionally mucus-/collagen-binding SpaCBA pilus, for the other operon (called spaFED) any native expression of the SpaFED-called pili is still the subject of some uncertainty. Irrespective of such considerations, we decided it would be of relevance or interest to decipher the gross structure of this pilus type, and as well assess its functional capabilities for cellular adhesion and immunostimulation. For this, and by following the approach we had used previously to explicate the immuno-properties of SpaCBA pili, we constructed nisin-inducible expression clones producing either wild-type or SpaF pilin-deleted surface-assembled L. rhamnosus GG SpaFED pili on Lactococcus lactis cells. Using these piliated lactococcal constructs, we found that the pilin-polymerized architecture of a recombinant-produced SpaFED pilus coincides with sequence-based functional predictions of the related pilins, and in fact is prototypical of those other sortase-dependent pilus-like structures thus far characterized for piliated Gram-positive bacteria. Moreover, we confirmed that among the different pilin subunits encompassing spaFED operon-encoded pili, the SpaF pilin is a main adhesion determinant, and when present in the assembled structure can mediate pilus binding to mucus, certain extracellular matrix proteins, and different gut epithelial cell lines. However, somewhat unexpectedly, when recombinant SpaFED pili are surface-attached, we found that they could not potentiate the existing lactococcal cell-induced immune responses so elicited from intestinal- and immune-related cells, but rather instead, they could dampen them. Accordingly, we have now provided the first phenotypical description of a spaFED pilus operon, and with that furthered the functional understanding of surface piliation for a particular gut-commensalic genre of piliated Gram-positive bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Adhesion / physiology*
  • Bacterial Proteins* / biosynthesis
  • Bacterial Proteins* / genetics
  • Fimbriae, Bacterial* / genetics
  • Fimbriae, Bacterial* / metabolism
  • Lacticaseibacillus rhamnosus / genetics*
  • Lacticaseibacillus rhamnosus / metabolism
  • Lactococcus lactis* / genetics
  • Lactococcus lactis* / metabolism
  • Operon*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics

Substances

  • Bacterial Proteins
  • Recombinant Proteins

Grants and funding

Financing of the operating expenses and costs for this project (including some salaries) was obtained from the Academy of Finland-funded Center of Excellence in Microbial Food Safety (CoE-MiFoSa) research program (Grant Nos. 118602 and 141140), and as well from Academy of Finland general research grants (Nos. 118165 and 277362)(http://www.aka.fi). Personal salary funding to Xia Yu was through the China Scholarship Council. Ravi Kant received some salary funding from The University of Helsinki Applied Bioscience (ABS) Graduate School (http://www.vetmed.helsinki.fi/abs/index.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.