Motivation: In 2001 and 2002, we published two papers (Bioinformatics, 17, 282--283, Bioinformatics, 18, 77--82) describing an ultrafast protein sequence clustering program called cd-hit. This program can efficiently cluster a huge protein database with millions of sequences. However, the applications of the underlying algorithm are not limited to only protein sequences clustering, here we present several new programs using the same algorithm including cd-hit-2d, cd-hit-est and cd-hit-est-2d. Cd-hit-2d compares two protein datasets and reports similar matches between them; cd-hit-est clusters a DNA/RNA sequence database and cd-hit-est-2d compares two nucleotide datasets. All these programs can handle huge datasets with millions of sequences and can be hundreds of times faster than methods based on the popular sequence comparison and database search tools, such as BLAST.

Availability: http://cd-hit.org

Contact: [email protected]

Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences

Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity.

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CRISPR provides acquired resistance against viruses in prokaryotes

Evolution of Protein Molecules

Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.

Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance

Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.

https://www.pnas.org/content/pnas/110/22/9066.full.pdf

Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

Fructo-Oligosaccharidverbrauchsverbindungen codierende Lactobacillus-acidophilus-Nukleinsäuren und Verwendungen dafür

L'invention porte sur des molecules, des fragments et des variants nucleotidiques possedant une activite de promoteur. L'invention se rapporte egalement a des vecteurs contenant la molecule nucleotidique precitee et a des cellules comprenant les vecteurs. L'invention concerne des procedes de fabrication et d'utilisation des molecules nucleotidiques precitees.

Compositions renfermant des sequences promoteurs et procedes d'utilisation

La presente invention a pour objet des methodes et des compositions pharmaceutiques destinees au traitement des symptomes associes a l'intolerance au lactose et a une amelioration globale de la sante gastro-intestinale. L'invention concerne des methodes et des compositions pharmaceutiques destinees a une amelioration globale de la sante gastro-intestinale ou a la diminution des symptomes de l'intolerance au lactose par l'administration au sujet en ayant besoin d'une composition pharmaceutique contenant un prebiotique, eventuellement en association avec une quantite efficace d'un microbe ou de microbes prebiotique(s).

Formulations prébiotiques et méthodes d'utilisation

L'invention concerne les molecules d'acide nucleique de la proteine liee au fructooligosaccharide (FOS) et leurs polypeptides, fragments et variantes. L'invention concerne egalement les proteines de fusion liees au FOS, les peptides antigeniques et les anticorps lies au FOS. L'invention concerne egalement des vecteurs d'expression recombinants contenant une molecule d'acide nucleique de l'invention et des cellules hotes dans lesquelles les vecteurs d'expression ont ete introduits. L'invention concerne enfin des procedes de production des polypeptides et leurs procedes d'utilisation.

Todd R. Klaenhammer

Papers

Fructo-Oligosaccharidverbrauchsverbindungen codierende Lactobacillus-acidophilus-Nukleinsäuren und Verwendungen dafür

Compositions renfermant des sequences promoteurs et procedes d'utilisation

Formulations prébiotiques et méthodes d'utilisation

Composes utilisant les acides nucleiques lactobacillus acidophilus codants pour le fructo-oligosaccharide et leurs utilisations

Nukleinsäurensequenzen, die für Proteine an der Zelloberfläche von Lactobacillus acidophilus kodieren und deren Verwendung