Database Authors
Wai Kit Ong1, Carol A Fulcher1, Anamika Kothari1, Pallavi Subhraveti1, Peter D Karp1, Ron Caspi1
1SRI International
Summary Some Lacticaseibacillus rhamnosus strains have beneficial effects on their host and are considered probiotics. Lacticaseibacillus rhamnosus GG (LGG) was originally isolated in 1983 from the intestinal tract of a healthy adult, and was initially used for the treatment of relapsing Clostridioides difficile colitis [Gorbach87]. The use of the strain was patented in 1985 by Sherwood Gorbach and Barry Goldin (hence the GG in its name) [Gorbach96]. Since then LGG has been used for various health effects including the prevention and treatment of gastro-intestinal infections and diarrhea and stimulation of immune responses, and is currently one of the most widely studied probiotic strains.

LGG produces exopolysaccharides rich in galactose residues and specific adhesive pili that enable it to adhere exceptionally well to the gastrointestinal mucosa [Kankainen09, Lebeer09]. It is able to withstand gastric acidity and bile salts effectively by producing anti-stress proteins [Conway87, Goldin92].

In addition to its antibacterial activity, LGG has several anti-inflammatory effects on its host [Khailova17]. The effect on the host's immune system is explained by the stimulation of different host cytokines such as TNF-α, IL-1β, IL-6, IL-10, IL-12, IFN-γ. LGG produces and secretes proteins (Msp1 and Msp2) that reduce the inflammatory state and apoptosis of intestinal epithelial cells [Yan07, Claes12]. Other apoptotic inhibition mechanisms are related to the modulation of cyclooxygenase-2 (COX-2) [Korhonen04, Ciorba12, Uribe18], leading to preclinical trials related to use of LGG against cancer [Banna17].

This Pathway/Genome Database (PGDB) was generated on 12-Jul-2016 by the PathoLogic [Karp10, Dale10, Caspi14] component of Pathway Tools software version 20.5 and MetaCyc version 20.0.

The primary data source for this dataset was the full genome sequence of Lacticaseibacillus rhamnosus GG, derived from RefSeq entry NC_013198.1 [Kankainen09].

The PGDB, which integrates the biochemical reaction network and metabolic pathways of the organism with its genome, was improved by limited manual curation.

Genome
RepliconTotal GenesProtein GenesRNA GenesPseudogenesSize (bp)NCBI Link
chromosome2,8002,70372253,010,111RefSeq:NC_013198
Ortholog data available?Yes
Database Contents
Genes2,800
Pathways208
Enzymatic Reactions990
Transport Reactions115
Polypeptides2,703
Protein Complexes85
Enzymes769
Transporters336
Compounds792
Transcription Units1,841
tRNAs57
Protein Features3,344
GO Terms102
Database Version29.0
Taxonomic Lineage cellular organisms
Bacteria <bacteria>
Terrabacteria group
Bacillota
Bacilli
Lactobacillales
Lactobacillaceae
Lacticaseibacillus
Lacticaseibacillus rhamnosus
Lacticaseibacillus rhamnosus GG
Genetic Code Number 11 -- Bacterial, Archaeal and Plant Plastid (same as Standard, except for alternate initiation codons)
NCBI BioProjectPRJNA224116
NCBI-Taxonomy568703
Relationship to Oxygenfacultative
Temperature Rangemesophile
Human Microbiome Body Sitegastrointestinal-tract
NCBI Genome Typerepresentative
Copyright SRI International 2016. All Rights Reserved.

References

Banna17: Banna GL, Torino F, Marletta F, Santagati M, Salemi R, Cannarozzo E, Falzone L, Ferrau F, Libra M (2017). "Lactobacillus rhamnosus GG: An Overview to Explore the Rationale of Its Use in Cancer." Front Pharmacol 8;603. PMID: 28919861

Caspi14: Caspi R, Altman T, Billington R, Dreher K, Foerster H, Fulcher CA, Holland TA, Keseler IM, Kothari A, Kubo A, Krummenacker M, Latendresse M, Mueller LA, Ong Q, Paley S, Subhraveti P, Weaver DS, Weerasinghe D, Zhang P, Karp PD (2014). "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases." Nucleic Acids Res. 42(1):D459-D471. PMID: 24225315

Ciorba12: Ciorba MA, Riehl TE, Rao MS, Moon C, Ee X, Nava GM, Walker MR, Marinshaw JM, Stappenbeck TS, Stenson WF (2012). "Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner." Gut 61(6);829-38. PMID: 22027478

Claes12: Claes IJ, Schoofs G, Regulski K, Courtin P, Chapot-Chartier MP, Rolain T, Hols P, von Ossowski I, Reunanen J, de Vos WM, Palva A, Vanderleyden J, De Keersmaecker SC, Lebeer S (2012). "Genetic and biochemical characterization of the cell wall hydrolase activity of the major secreted protein of Lactobacillus rhamnosus GG." PLoS One 7(2);e31588. PMID: 22359601

Conway87: Conway PL, Gorbach SL, Goldin BR (1987). "Survival of lactic acid bacteria in the human stomach and adhesion to intestinal cells." J Dairy Sci 70(1);1-12. PMID: 3106442

Dale10: Dale JM, Popescu L, Karp PD (2010). "Machine learning methods for metabolic pathway prediction." BMC Bioinformatics 11;15. PMID: 20064214

Goldin92: Goldin BR, Gorbach SL, Saxelin M, Barakat S, Gualtieri L, Salminen S (1992). "Survival of Lactobacillus species (strain GG) in human gastrointestinal tract." Dig Dis Sci 37(1);121-8. PMID: 1728516

Gorbach87: Gorbach SL, Chang TW, Goldin B (1987). "Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG." Lancet 2(8574);1519. PMID: 2892070

Gorbach96: Gorbach, S. L. (1996). "The Discovery of Lactobacillus GG." Nutr Today 31(6): (suppl.): 2S-4S.

Kankainen09: Kankainen M, Paulin L, Tynkkynen S, von Ossowski I, Reunanen J, Partanen P, Satokari R, Vesterlund S, Hendrickx AP, Lebeer S, De Keersmaecker SC, Vanderleyden J, Hamalainen T, Laukkanen S, Salovuori N, Ritari J, Alatalo E, Korpela R, Mattila-Sandholm T, Lassig A, Hatakka K, Kinnunen KT, Karjalainen H, Saxelin M, Laakso K, Surakka A, Palva A, Salusjarvi T, Auvinen P, de Vos WM (2009). "Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein." Proc Natl Acad Sci U S A 106(40);17193-8. PMID: 19805152

Karp10: Karp PD, Paley SM, Krummenacker M, Latendresse M, Dale JM, Lee TJ, Kaipa P, Gilham F, Spaulding A, Popescu L, Altman T, Paulsen I, Keseler IM, Caspi R (2010). "Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology." Brief Bioinform 11(1);40-79. PMID: 19955237

Khailova17: Khailova L, Baird CH, Rush AA, Barnes C, Wischmeyer PE (2017). "Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates inflammatory response and homeostasis of spleen and colon in experimental model of Pseudomonas aeruginosa pneumonia." Clin Nutr 36(6);1549-1557. PMID: 27745813

Korhonen04: Korhonen R, Kosonen O, Korpela R, Moilanen E (2004). "The expression of COX2 protein induced by Lactobacillus rhamnosus GG, endotoxin and lipoteichoic acid in T84 epithelial cells." Lett Appl Microbiol 39(1);19-24. PMID: 15189283

Lebeer09: Lebeer S, Verhoeven TL, Francius G, Schoofs G, Lambrichts I, Dufrene Y, Vanderleyden J, De Keersmaecker SC (2009). "Identification of a Gene Cluster for the Biosynthesis of a Long, Galactose-Rich Exopolysaccharide in Lactobacillus rhamnosus GG and Functional Analysis of the Priming Glycosyltransferase." Appl Environ Microbiol 75(11);3554-63. PMID: 19346339

Uribe18: Uribe G, Villeger R, Bressollier P, Dillard RN, Worthley DL, Wang TC, Powell DW, Urdaci MC, Pinchuk IV (2018). "Lactobacillus rhamnosus GG increases cyclooxygenase-2 expression and prostaglandin E2 secretion in colonic myofibroblasts via a MyD88-dependent mechanism during homeostasis." Cell Microbiol 20(11);e12871. PMID: 29920917

Yan07: Yan F, Cao H, Cover TL, Whitehead R, Washington MK, Polk DB (2007). "Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth." Gastroenterology 132(2);562-75. PMID: 17258729

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