Abstract: Methods and compositions are provided for transferring a genetic circuit from one prokaryotic cell (“donor cell”) to another prokaryotic cell (“recipient cell” or “target cell”). The genetic circuit contains a nucleic acid of interest under the transcriptional control of a repressor binding sequence. The nucleic acid sequence of interest may encode a protein or RNA of interest.

Abstract: The present invention relates to the delivery of a payload by bacterial delivery vehicle, i.e. the encapsulation and the delivery of a single plasmid by different bacterial virus particles. More specifically, the present invention concerns a pharmaceutical composition comprising a payload packaged in at least two different bacterial delivery vehicles and a method of production thereof.

Abstract: The present invention relates to a vector, preferably included in a delivery vehicle, comprising no more than 100, preferably no more than 10, restriction sites recognized by the restriction enzymes encoded by each bacterium of a group of bacteria of interest. The invention also relates to the use of said vector, preferably included in a delivery vehicle, as a drug, especially in the treatment of a disease in a patient in need thereof.

Abstract: The present invention concerns nucleic acids of interest for modulating the microbiome of a host, to vectors encoding said nucleic acids and to methods for in vivo modulating the microbiome of a subject by delivering said nucleic acid of interest.

Abstract: The present invention relates to a vector, preferably included in a delivery vehicle, comprising no more than (100), preferably no more than (10), restriction sites recognized by the restriction enzymes encoded by each bacterium of a group of bacteria of interest. The invention also relates to the use of said vector, preferably included in a delivery vehicle, as a drug, especially in the treatment of a disease in a patient in need thereof.

Abstract: The present invention concerns a postbiotic composition comprising at least one postbiotic and at least one bacteriocin and/or endolysin, preferably formulated, and a postbiotic composition comprising at least one postbiotic and at least one bacteriocin and/or endolysin for use as a medicament, wherein said postbiotic is preferably a microbial lysate, preferably obtained from microorganisms heterologously expressing said at least one bacteriocin and/or endolysin and wherein said at least one postbiotic and said at least one bacteriocin and/or endolysin have a synergistic effect in the therapeutic treatment.

Abstract: The invention encompasses compositions, kits and methods for modifying bacteria, preferably naturally occurring bacteria, in situ. These can be used to treat, prevent or cure microbiome-associated diseases or disorders by modulating the molecules expressed and/or secreted by bacterial populations of the microbiome in a specific manner. The genomic modifications can modify the interactions between part or all of these populations and the host in a way that decreases their deleterious potential on host health. The compositions, kits and methods of the invention do not result in the direct death of these populations or a direct significant inhibition of their growth. The invention further includes methods for screening for genetic modifications in the bacteria, for determining the efficiency of vectors at inducing these genetic mutations, and for determining the effects of these mutations on bacterial growth.

Abstract: The present invention concerns nucleic acids of interest for modulating the microbiome of a host, to vectors encoding the nucleic acids and to methods for in vivo modulating the microbiome of a subject by delivering the nucleic acids of interest.

Abstract: The invention relates to methods, kits, and compositions for reducing the level of or eliminating a nucleic acid vector in situ. The invention encompasses compositions and methods for selectively eradicating nucleic acid vectors in the microbiota using packaged phagemids. The microbiota can be intestinal and the packaged phagemids can be administered orally. The phagemid encodes a nuclease or other enzyme that genetically modifies the nucleic acid vector so that the nucleic acid vector can be inactivated or eliminated.

Abstract: The present disclosure relates generally to methods and compositions for transferring a genetic circuit from one prokaryotic cell (“donor cell”) to another prokaryotic cell (“recipient cell” or “target cell” which are used interchangeably herein). More specifically, the present disclosure relates to prokaryotic donor cells comprising (i) a genetic circuit of interest and (ii) one or more expressed transcriptional repressor proteins and the use of said donor cells in the efficient transfer of the genetic circuit into a prokaryotic recipient cell. The genetic circuit includes nucleic acid sequences encoding a RNA molecule or protein of interest.

Abstract: The invention relates to methods, kits and compositions for reducing the level of or eliminating Bacteroides in situ. The invention encompasses methods of preventing myocarditis, treating myocarditis or dilated cardiomyopathy, or limiting progression of myocarditis toward dilated cardiomyopathy in a subject in need thereof, comprising reducing the amount of Bacteroides sp. in the subject. The invention further encompasses methods of diagnosis of a subject as having myocarditis or dilated cardiomyopathy. The invention also encompasses compositions preventing myocarditis, treating myocarditis or dilated cardiomyopathy, or limiting progression of myocarditis toward dilated cardiomyopathy in a subject in need thereof.

Abstract: The invention relates to methods, kits, and compositions for reducing the level of or eliminating antimicrobial resistant (AMR) bacteria in situ. The invention encompasses compositions and methods for selectively eradicating antibiotic resistance in bacteria that carry antibiotic resistance genes in the microbiota using packaged phagemids. The microbiota can be intestinal and the packaged phagemids can be administered to a healthy subject or patient, for example, orally, rectally (e.g., in an enema), vaginally, nasally or to the skin. The phagemid encodes a nuclease or other enzyme that genetically modifies the DNA encoding the antibiotic resistance gene so that the bacteria can then be eliminated with the antibiotic.

Abstract: The present invention concerns a method for the cosmetic caring of the skin and/or mucosa, comprising applying a postbiotic composition comprising at least one postbiotic and at least one bacteriocin and/or endolysin, wherein said postbiotic is preferably a bacterial lysate preferably obtained from bacteria heterologously expressing said at least one bacteriocin and/or endolysin and wherein said postbiotic and said at least one bacteriocin and/or endolysin have a synergistic effect in the cosmetic caring method.

Abstract: The present invention concerns a postbiotic composition comprising at least one postbiotic and at least one bacteriocin and/or endolysin, preferably formulated, and a postbiotic composition comprising at least one postbiotic and at least one bacteriocin and/or endolysin for use as a medicament, wherein said postbiotic is preferably a microbial lysate, preferably obtained from microorganisms heterologously expressing said at least one bacteriocin and/or endolysin and wherein said at least one postbiotic and said at least one bacteriocin and/or endolysin have a synergistic effect in the therapeutic treatment.

Abstract: The invention encompasses compositions, kits and methods for modifying bacteria, preferably naturally occurring bacteria, in situ. These can be used to treat, prevent or cure microbiome-associated diseases or disorders by modulating the molecules expressed and/or secreted by bacterial populations of the microbiome in a specific manner. The genomic modifications can modify the interactions between part or all of these populations and the host in a way that decreases their deleterious potential on host health. The compositions, kits and methods of the invention do not result in the direct death of these populations or a direct significant inhibition of their growth. The invention further includes methods for screening for genetic modifications in the bacteria, for determining the efficiency of vectors at inducing these genetic mutations, and for determining the effects of these mutations on bacterial growth.

Abstract: The present disclosure provides a chimeric receptor binding protein (RBP) resistant to proteolytic digestion wherein said RBP comprises a portion of a receptor binding protein derived from a bacteriophage fused through a designed linker region consisting of 1 to 70 amino acids, to a portion of a receptor binding protein derived from a different bacteriophage, wherein said linker region is designed to be resistant to proteolytic digestion.

Abstract: The present invention concerns a method to modulate the level of or to modify a target molecule in a subject or an environment, said method comprising: administering in said subject or providing to said environment an engineered bacterial strain comprising (i) a heterologous or engineered nucleic acid involved in the expression of a molecule of interest, wherein the expression of said molecule of interest modulates directly or indirectly the level of or modify the target molecule in said subject or environment, and (ii) a heterologous or engineered gene or gene set involved in the import and/or metabolism of a rare carbohydrate, wherein said heterologous gene or gene set comes from another species than the engineered bacterial strain; and further administering to said subject, or providing to said environment, said rare carbohydrate; whereby the level of the target molecule in said subject or environment is modulated or the target molecule is modified in said subject or environment.

Abstract: A method for the cosmetic caring of the skin and/or mucosa, comprising applying a postbiotic composition comprising at least one postbiotic and at least one bacteriocin and/or endolysin, wherein the postbiotic is preferably a bacterial lysate preferably obtained from bacteria heterologously expressing the at least one bacteriocin and/or endolysin and wherein the postbiotic and the at least one bacteriocin and/or endolysin have a synergistic effect in the cosmetic caring method.

Abstract: The present invention concerns a method to modulate the level of or to modify a target molecule in a subject or an environment, said method comprising: administering in said subject or providing to said environment an engineered bacterial strain comprising (i) a heterologous or engineered nucleic acid involved in the expression of a molecule of interest, wherein the expression of said molecule of interest modulates directly or indirectly the level of or modify the target molecule in said subject or environment and (ii) an autologous gene or gene set involved in the import and/or metabolism of a milk oligosaccharide; and further administering to said subject, or providing to said environment, said milk oligosaccharide; whereby the level of the target molecule in said subject or environment is modulated or the target molecule is modified in said subject or environment.

Abstract: The invention encompasses compositions, kits and methods for modifying bacteria, preferably naturally occurring bacteria, in situ. These can be used to treat, prevent or cure microbiome-associated diseases or disorders by modulating the molecules expressed and/or secreted by bacterial populations of the microbiome in a specific manner. The genomic modifications can modify the interactions between part or all of these populations and the host in a way that decreases their deleterious potential on host health. The compositions, kits and methods of the invention do not result in the direct death of these populations or a direct significant inhibition of their growth. The invention further includes methods for screening for genetic modifications in the bacteria, for determining the efficiency of vectors at inducing these genetic mutations, and for determining the effects of these mutations on bacterial growth.