Identification of Genes Associated with the Long-Gut-Persistence Phenotype of the Probiotic
            <i>Lactobacillus johnsonii</i>
            Strain NCC533 Using a Combination of Genomics and Transcriptome Analysis

Denou, Emmanuel; Pridmore, R. David; Berger, Bernard; Panoff, Jean-Michel; Arigoni, Fabrizio; Brüssow, Harald

doi:10.1128/jb.01637-07

Cited by 164 publications

(136 citation statements)

References 55 publications

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“…Previous transcriptomic studies carried out in Lactobacillus plantarum and L. johnsonii while colonizing the gut showed an up-regulation of a large set of genes related to carbohydrate transport and metabolism, indicating a global recruitment of sugar-utilization enzymes for energy supply and a change in carbohydrate-utilization pathways to adapt to sugar limitation (15,53,54). In L. plantarum, energy production from maltose, melibiose, and lactose is activated, as is the import of mannose and cellobiose in the cecum of monocolonized mice (54).…”

Section: Discussionmentioning

confidence: 99%

“…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). 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).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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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“…Lactobacillus johnsonii is a member of this bacterial order that resides in the human gut and is a fatty acid auxotroph (47). L. johnsonii lacks the genes to carry out FASII and requires exogenous fatty acids from either the host or the gut microbial community for membrane lipid synthesis (48).…”

Section: Exogenous Fatty Acid Metabolism By Gram-positive Bacteriamentioning

confidence: 99%

How Bacterial Pathogens Eat Host Lipids: Implications for the Development of Fatty Acid Synthesis Therapeutics

Yao

Rock

2015

Journal of Biological Chemistry

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Bacterial type II fatty acid synthesis (FASII) is a target for the development of novel therapeutics. Bacteria incorporate extracellular fatty acids into membrane lipids, raising the question of whether pathogens use host fatty acids to bypass FASII and defeat FASII therapeutics. Some pathogens suppress FASII when exogenous fatty acids are present to bypass FASII therapeutics. FASII inhibition cannot be bypassed in many bacteria because essential fatty acids cannot be obtained from the host. FASII antibiotics may not be effective against all bacteria, but a broad spectrum of Gram-negative and -positive pathogens can be effectively treated with FASII inhibitors. The Biological ProblemThe discovery of antibiotics for the treatment of infectious bacterial diseases has led to significant improvements in human health. The success of these broad-spectrum "miracle drugs" is reflected in the dearth of new antibiotic classes introduced in the last 30 years (1). However, the steady increase in bacterial antibiotic resistance to all antimicrobials in clinical use (2, 3) has caused infectious bacterial diseases to re-emerge as a serious threat to human health. These resistant bacteria are a clear and present danger that will require the discovery of new antibiotic targets and drugs to combat (4). Fatty acid synthesis is a vital facet of bacterial physiology, and its essentiality for membrane formation makes it an attractive target for drug discovery (5). Nature has exploited this dependence to produce a variety of natural products that target bacterial fatty acid synthesis (5-7). Selective targeting of the bacterial pathway is possible due to the significant differences in the structure of eukaryotic and bacterial fatty acid synthesis systems. Mammalian type I fatty acid synthase is a large, multifunctional peptide that elongates acetyl-CoA to produce a single product, palmitic acid (8).In the bacterial type II system (FASII), 2 each enzymatic step is carried out by a discrete, monofunctional enzyme ( Fig. 1) (9).Many inhibitors targeting FASII enzymes have been made in the past two decades, and several of these inhibitors are effective antibiotics both in vitro and in animal models (10 -13). Two of these compounds, AFN-1252 and CG400549, have proven efficacy in human clinical trials, providing direct evidence that targeting FASII components can result in effective therapeutic agents (14,15).Most bacteria are able to incorporate extracellular fatty acids into their membrane phospholipids, leading to the important question of whether this property will allow them to circumvent FASII inhibitors by acquiring the fatty acids they need from the host. Brinster et al. (16) argued that FASII is not an antibacterial target in Gram-positive bacteria due to the ability of Streptococcus agalactiae to circumvent FASII inhibitors when supplied with exogenous host-derived fatty acids. However, the situation is more complex because not all Gram-positive bacteria have the same fatty acid structures as mammals, and the conclusion is not co...

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“…Consequently, a bacterial "species" has to be defined within the framework of population genetics, and the bacterial clone takes a cornerstone position in the discussion of bacterial evolution (24). Associating the different genotypes with specific phenotypes is now an important task for understanding the ecological physiology in a given bacterial species (13). A clear-cut clonal population structure has been documented for some pathogenic bacteria.…”

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The Role of Prophage for Genome Diversification within a Clonal Lineage ofLactobacillus johnsonii: Characterization of the Defective Prophage LJ771

et al. 2008

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Two independent isolates of the gut commensal Lactobacillus johnsonii were sequenced. These isolates belonged to the same clonal lineage and differed mainly by a 40.8-kb prophage, LJ771, belonging to the Sfi11 phage lineage. LJ771 shares close DNA sequence identity with Lactobacillus gasseri prophages. LJ771 coexists as an integrated prophage and excised circular phage DNA, but phage DNA packaged into extracellular phage particles was not detected. Between the phage lysin gene and attR a likely mazE ("antitoxin")/pemK ("toxin") gene cassette was detected in LJ771 but not in the L. gasseri prophages. Expressed pemK could be cloned in Escherichia coli only together with the mazE gene. LJ771 was shown to be highly stable and could be cured only by coexpression of mazE from a plasmid. The prophage was integrated into the methionine sulfoxide reductase gene (msrA) and complemented the 5 end of this gene, creating a protein with a slightly altered N-terminal sequence. The two L. johnsonii strains had identical in vitro growth and in vivo gut persistence phenotypes. Also, in an isogenic background, the presence of the prophage resulted in no growth disadvantage.

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Identification of Genes Associated with the Long-Gut-Persistence Phenotype of the Probiotic Lactobacillus johnsonii Strain NCC533 Using a Combination of Genomics and Transcriptome Analysis

Cited by 164 publications

References 55 publications

Functional genomics of Lactobacillus casei establishment in the gut

Functional genomics of Lactobacillus casei establishment in the gut

How Bacterial Pathogens Eat Host Lipids: Implications for the Development of Fatty Acid Synthesis Therapeutics

The Role of Prophage for Genome Diversification within a Clonal Lineage ofLactobacillus johnsonii: Characterization of the Defective Prophage LJ771

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