Functional genome analysis of
            <i>Bifidobacterium breve</i>
            UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor

Motherway, Mary O’Connell; Zomer, Aldert; Leahy, Sinead C.; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J.; O’Brien, Frances; Flynn, Kiera; Casey, Patrick G.; Muñoz, José Antonio Moreno; Kearney, Breda; Houston, Aileen; O’Mahony, Cáitlín; Higgins, Desmond G.; Shanahan, Fergus; Palva, Airi; Vos, Willem M. de; Fitzgerald, Gerald F.; Ventura, Marco; O’Toole, Paul W.; Sinderen, Douwe van

doi:10.1073/pnas.1105380108

Cited by 324 publications

(338 citation statements)

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“…Genes encoding a mannose-sensitive hemagglutinin (MSHA)-like Type-IVa pilus were also identified in both symbionts and the Osedax Rs1 symbiont uniquely possesses a Type-IVb tight adherence (tad) pilus-encoding gene cluster. These pili function in surface attachment, biofilm formation and colonization and are considered a key virulence factor in Vibrio cholerae and other pathogenic bacteria (Chiavelli et al, 2001;Dalisay et al, 2006;Tomich et al, 2007;O'Connell Motherway et al, 2011). Both symbionts possess genes with homology Figure 1 (dive DR471).…”

Section: Genomic Implications For Intracellular Lifementioning

confidence: 99%

Genomic versatility and functional variation between two dominant heterotrophic symbionts of deep-sea Osedax worms

Goffredi

Zhang

et al. 2013

The ISME Journal

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An unusual symbiosis, first observed at B3000 m depth in the Monterey Submarine Canyon, involves gutless marine polychaetes of the genus Osedax and intracellular endosymbionts belonging to the order Oceanospirillales. Ecologically, these worms and their microbial symbionts have a substantial role in the cycling of carbon from deep-sea whale fall carcasses. Microheterogeneity exists among the Osedax symbionts examined so far, and in the present study the genomes of the two dominant symbionts, Rs1 and Rs2, were sequenced. The genomes revealed heterotrophic versatility in carbon, phosphate and iron uptake, strategies for intracellular survival, evidence for an independent existence, and numerous potential virulence capabilities. The presence of specific permeases and peptidases (of glycine, proline and hydroxyproline), and numerous peptide transporters, suggests the use of degraded proteins, likely originating from collagenous bone matter, by the Osedax symbionts. 13 C tracer experiments confirmed the assimilation of glycine/ proline, as well as monosaccharides, by Osedax. The Rs1 and Rs2 symbionts are genomically distinct in carbon and sulfur metabolism, respiration, and cell wall composition, among others. Differences between Rs1 and Rs2 and phylogenetic analysis of chemotaxis-related genes within individuals of symbiont Rs1 revealed the influence of the relative age of the whale fall environment and support possible local niche adaptation of 'free-living' lifestages. Future genomic examinations of other horizontally-propogated intracellular symbionts will likely enhance our understanding of the contribution of intraspecific symbiont diversity to the ecological diversification of the intact association, as well as the maintenance of host diversity.

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Section: Genomic Implications For Intracellular Lifementioning

confidence: 99%

Genomic versatility and functional variation between two dominant heterotrophic symbionts of deep-sea Osedax worms

Goffredi

Zhang

et al. 2013

The ISME Journal

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“…Adhesion to cell surface-associated structures has been shown to be an important determinant of metabolic and immune interactions for both commensal and pathogenic bacteria in animal models of colonisation and disease. 79,80 Motherway et al 81 described type IVb tight adherence pilus expression and associated genetic determinants in B. breve UCC2003 using a mouse model of colonisation. The epitopes for pilus adhesion in this mouse model have yet to be identified.…”

Section: Identification Of Bifidobacterium Breve Bbg-001mentioning

confidence: 99%

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial

Costeloe

Bowler

Brocklehurst

et al. 2016

Health Technol Assess

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BackgroundNecrotising enterocolitis (NEC) and late-onset sepsis remain important causes of death and morbidity in preterm babies. Probiotic administration might strengthen intestinal barrier function and provide protection; this is supported by published meta-analyses, but there is a lack of large well-designed trials.ObjectiveTo test the use of the probioticBifidobacterium brevestrain BBG-001 to prevent NEC, late-onset sepsis and death in preterm babies while monitoring probiotic colonisation of participants.DesignDouble-blind, randomised, placebo-controlled trial.SettingRecruitment was carried out in 24 hospitals, and the randomisation programme used a minimisation algorithm. Parents, clinicians and outcome assessors were blinded to the allocation.ParticipantsBabies born between 23 and 30 weeks’ gestation and randomised within 48 hours of birth. Exclusions included life-threatening or any gastrointestinal malformation detected within 48 hours of birth and no realistic chance of survival.InterventionsActive intervention: 1 ml ofB. breveBBG-001 in one-eighth-strength infant formula Neocate®(Nutricia Ltd, Trowbridge, UK), (6.7 × 107to 6.7 × 109colony-forming units) per dose administered enterally. Placebo: 1 ml of one-eighth-strength infant formula Neocate. Started as soon as practicable and continued daily until 36 weeks’ postmenstrual age.Main outcome measuresPrimary outcomes were an episode of bloodstream infection, with any organism other than a skin commensal, in any baby between 72 hours and 46 weeks’ postmenstrual age; an episode of NEC Bell stage ≥ 2 in any baby; and death before discharge from hospital. Secondary outcomes included stool colonisation withB. breve.ResultsIn total, 654 babies were allocated to receive probiotic and 661 to receive placebo over 37 months from July 2010. Five babies were withdrawn; 650 babies from the probiotic group and 660 from the placebo group were included in the primary analysis. Baseline characteristics were well balanced. There was no evidence of benefit for the primary outcomes {sepsis: 11.2% vs. 11.7% [adjusted relative risk (RR) 0.97, 95% confidence interval (CI) 0.73 to 1.29]; NEC Bell stage ≥ 2: 9.4% vs. 10.0% [adjusted RR 0.93, 95% CI 0.68 to 1.27]; and death: 8.3% vs. 8.5% [adjusted RR 0.93, 95% CI 0.67 to 1.30]}.B. brevecolonisation status was available for 1186 (94%) survivors at 2 weeks’ postnatal age, of whom 724 (61%) were positive: 85% of the probiotic group and 37% of the placebo group. There were no differences for subgroup analyses by minimisation criteria and by stool colonisation withB. breveat 2 weeks. No harms associated with the interventions were reported.LimitationsCross-colonisation of the placebo arm could have reduced statistical power and confounded results; analyses suggest that this did not happen.ConclusionsThis is the largest trial to date of a probiotic intervention. It shows no evidence of benefit and does not support routine use of probiotics for preterm infants.Future work recommendationsThe increasing understanding of the pathogenesis of NEC and sepsis will inform the choice of probiotics for testing and better define the target population. Future Phase III trials should incorporate monitoring of the quality and viability of the intervention and colonisation rates of participants; cluster design should be considered.Trial registrationCurrent Controlled Trials ISRCTN05511098 and EudraCT 2006-003445-17.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 66. See the NIHR Journals Library website for further project information.

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“…As it was done for pathogens, it is essential to develop the cellular microbiology of symbionts and particularly to identify the genes required for their establishment and persistence in the gut. Transcriptomic profiling identified up-regulated genes linked to metabolic functions, stress responses, and pili synthesis during early colonization (11)(12)(13). Comparative genomics among Lactobacilli identified strain-specific candidate genes for extended colonization: In Lactobacillus rhamnosus, persistence was attributed to an spaCBA locus encoding LPXTG-like pilins (14), and in Lactobacillus johnsonii it was attributed to specific glycosyltransferases, a phosphotransfer system, and a protease (15).…”

mentioning

confidence: 99%

Functional genomics of Lactobacillus casei establishment in the gut

Licandro

Scornec

Pédron

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Although the composition of the gut microbiota and its symbiotic contribution to key host physiological functions are well established, little is known as yet about the bacterial factors that account for this symbiosis. We selected Lactobacillus casei as a model microorganism to proceed to genomewide identification of the functions required for a symbiont to establish colonization in the gut. As a result of our recent development of a transposonmutagenesis tool that overcomes the barrier that had prevented L. casei random mutagenesis, we developed a signature-tagged mutagenesis approach combining whole-genome reverse genetics using a set of tagged transposons and in vivo screening using the rabbit ligated ileal loop model. After sequencing transposon insertion sites in 9,250 random mutants, we assembled a library of 1,110 independent mutants, all disrupted in a different gene, that provides a representative view of the L. casei genome. By determining the relative quantity of each of the 1,110 mutants before and after the in vivo challenge, we identified a core of 47 L. casei genes necessary for its establishment in the gut. They are involved in housekeeping functions, metabolism (sugar, amino acids), cell wall biogenesis, and adaptation to environment. Hence we provide what is, to our knowledge, the first global functional genomics analysis of L. casei symbiosis.commensalism | Lactic acid bacteria T he pioneering studies that led to the characterization of the gut microbiota were reviewed in 2001 (1). These studies and recent investigations have revealed mutualistic functions (2), including a barrier effect against allogenic microbes (3), fermentation of complex sugars (4, 5), and maturation and homeostasis of the immune system (6). Recent metagenomic studies have revealed an extraordinary diversity of genes constituting the gut microbiome (7), opening the way to correlative studies linking microbiome diversity, homeostasis, and diseases (5,8,9).In parallel, some representative species, i.e., "model symbionts," now are being studied functionally (10). As it was done for pathogens, it is essential to develop the cellular microbiology of symbionts and particularly to identify the genes required for their establishment and persistence in the gut. Transcriptomic profiling identified up-regulated genes linked to metabolic functions, stress responses, and pili synthesis during early colonization (11-13). Comparative genomics among Lactobacilli identified strain-specific candidate genes for extended colonization: In Lactobacillus rhamnosus, persistence was attributed to an spaCBA locus encoding LPXTG-like pilins (14), and in Lactobacillus johnsonii it was attributed to specific glycosyltransferases, a phosphotransfer system, and a protease (15). Otherwise, a functional in vivo screening based on the expression of a genomic library of Bacteroides fragilis identified a locus encoding polysaccharide utilization as essential for stable colonization of murine colonic crypts (16). Alternatively, colonization of germ-free mic...

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Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor

Cited by 324 publications

References 58 publications

Genomic versatility and functional variation between two dominant heterotrophic symbionts of deep-sea Osedax worms

Genomic versatility and functional variation between two dominant heterotrophic symbionts of deep-sea Osedax worms

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial

Functional genomics of Lactobacillus casei establishment in the gut

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