Understanding the molecular mechanisms of gut commensal colonization, pathogen exclusion, and host-microbe interplay.

Project: Research project

Description

An Academy of Finland-funded research project (No. 277362) authored by Adjunct Prof. (Docent) Ingemar von Ossowski and awarded to Prof. (retired) Airi Palva.*

BACKGROUND AND DESCRIPTION: The myriad of “intestinal-friendly” bacteria residing in the gut of humans and other mammals is a normal part of natural digestive health and well-being. For this, accumulating world-wide research suggests that these different bacterial genera and species (called collectively the gut microbiota) represent a beneficial storehouse of metabolic, protective, and structural processes. However, the properties and behavior of most individual bacteria remain obscure, particularly the manner in which some can permanently colonize the intestine. The funded research project will address this latter shortcoming by studying the gut colonization behavior of a paradigm commensal bacterium (Lactobacillus ruminis) and its ability to coexist as an indigenous member of the gut microbiota. Here, the ultimate goal will be to correlate the contributive impact of its ecological niche factors and their extracellular matrix (ECM) adhesion capacity to its characteristic gut autochthony. Project objectives will involve (i) generating high-throughput genome data, thus laying groundwork for in silico comparative and predictive analyses; (ii) functional and structural characterization of novel niche factors and traits; and (iii) probing the host-cell interactions (e.g., by examining the propensity to localize in the gut, counteract invading intestinal pathogens, and trigger protective aspects of host immunity). As an expected outcome, this study should advance the biological understanding of one facet of the many interconnected roles and functions played by gut microbes.

PARTICIPANTS:
Prof. (retired) Airi Palva; project awardee
Adjunct Prof. (Docent) Ingemar von Ossowski; project author
MSc Ravi Kant; doctoral student and bioinformatics specialist
MSc Xia Yu; doctoral student
Dr. Silja Åvall-Jääskeläinen; university lecturer
Dr. Ulla Hynönen; postdoctoral fellow

PAST CONTRIBUTORS AND PARTICIPANTS:
Dr. Johanna Rintahaka; postdoctoral fellow
Dr. Agneta Lindholm; postdoctoral fellow
Annukka Jaatinen; MSc project student
Outi Lyytinen; laboratory assistant

PUBLICATIONS: (project-related)

von Ossowski I (2017) Novel molecular insights about lactobacillar sortase-dependent piliation. Int J Mol Sci 18(7):1551

Kant R, Palva A, von Ossowski I (2017) An in silico pan-genomic probe for the molecular traits behind Lactobacillus ruminis gut autochthony. PLoS ONE 12(4):e0175541

Yu X, Åvall-Jääskeläinen S, Koort J, Lindholm A, Rintahaka J, von Ossowski I, Palva A, Hynönen U (2017) A comparative characterization of different host-sourced Lactobacillus ruminis strains and their adhesive, inhibitory, and immunomodulating functions. Front Microbiol 8:657

Yu X, Rintahaka J, Jaatinen A, Hynönen U, Åvall-Jääskeläinen S, Lindholm A, von Ossowski I, Palva A (2016) Phenotypic characterization of a lactobacillar fimbrial operon through recombinant expression in Lactococcus lactis. J Clin Gastroenterol 50(Suppl 2):S209

Yu X, Jaatinen A, Rintahaka J, Hynönen U, Lyytinen O, Kant R, Åvall-Jääskeläinen S, von Ossowski I, Palva A (2015) Human gut-commensalic Lactobacillus ruminis ATCC 25644 displays sortase-assembled surface piliation: Phenotypic characterization of its fimbrial operon through in silico predictive analysis and recombinant expression in Lactococcus lactis. PLoS ONE 10(12):e0145718

PUBLICATIONS: (ancillary)

Mishra AK, Megta AK, Palva A, von Ossowski I, Krishnan V (2017) Crystallization and X-ray diffraction analysis of SpaE, a basal pilus protein from gut-adapted Lactobacillus rhamnosus GG. Acta Crystallogr F Struct Biol Commun F73:321-327

Chaurasia P, Pratap S, von Ossowski I, Palva A, Krishnan V (2016) New insights about pilus formation in gut-adapted Lactobacillus rhamnosus GG from the crystal structure of the SpaA backbone-pilin subunit. Sci Rep 6:28664

Kant A, von Ossowski I, Palva A, Krishnan V (2016) Crystallization and X-ray crystallographic analysis of the adhesive SpaC pilin subunit in the SpaCBA pilus of gut-adapted Lactobacillus rhamnosus GG. Protein Pept Lett 23:365-371

Chaurasia P, von Ossowski I, Palva A, Krishnan V (2015) Purification, crystallization, and preliminary X-ray diffraction analysis of SpaD, a backbone-pilin subunit encoded by the fimbrial spaFED operon in Lactobacillus rhamnosus GG. Acta Crystallogr F Struct Biol Commun F71:103-106

Rintahaka J, Yu X, Kant R, Palva A, von Ossowski I (2014) Phenotypical analysis of the Lactobacillus rhamnosus GG fimbrial spaFED operon: Surface expression and functional characterization of recombinant SpaFED pili in Lactococcus lactis. PLoS ONE 9(11):e113922

Kant R, Rintahaka J, Yu X, Sigvart-Mattila P, Paulin L, Mecklin J-P, Saarela M, Palva A, von Ossowski I (2014) A comparative pan-genome perspective of niche-adaptable cell-surface protein phenotypes in Lactobacillus rhamnosus. PLoS ONE 9(7):e102762

* A note of gratitude and appreciation is extended to the Academy of Finland for their decision to fund this research project.

StatusActive
Effective start/end date01/09/201431/08/2018

ID: 51424374