Intrexon Actobiotics N.v.

Actogenix N.v.

Klaas Vandenbroucke

Lothar Steidler

Karolien Van Huynegem

Pieter Rottiers

Sabine Neirynck

Dirk Iserentant

The present disclosure provides genetically modified microorganisms (e.g., bacteria or yeast) with enhanced mucin-binding and/or cell-adhesion properties. For example, the present disclosure provides bacteria exhibiting increased in vitro binding to Caco-2 cells, and increased in vitro binding to mucins. Such microorganisms (e.g., bacteria) can be used, e.g., to deliver bioactive polypeptides to the gastrointestinal tract of a mammalian subject. Modifying the microorganism in the described manner allows for the modulation of gastrointestinal retention and transit times for the microorganism (e.g., bacterium). Exemplary microorganisms (e.g., lactic acid bacteria, such as) contain an exogenous nucleic acid encoding a fusion protein containing a cell-adherence polypeptide, such as CmbA, and a mucin-binding polypeptide, such as a trefoil factor (TFF), e.g., human TFF3. The current disclosure further provides method for making and using the described microorganisms (e.g., bacteria).

Mucoadhesive microorganism

The invention relates to polycistronic expression in gram-positive bacterium and in particular concerns polycistronic expression units comprising one or more gene endogenous to the gram-positive bacterium transcriptionally coupled to one or more genes exogenous to the bacterium.

Polycistronic expression system for bacteria

The present invention relates to gram positive bacteria with increased stress resistance and/or improved storage characteristics. In particular, the invention relates to gram positive bacterium which accumulate intracellular trehalose. The gram positive bacterium according to the invention lack cellobiose-specific PTS system IIC component (PtcC) activity. The gram positive bacterium may further lack trehalose 6-phosphate phosphorylase (TrePP) activity. The gram positive bacterium may further overexpress trehalose transporters. The invention further relates to compositions comprising such gram positive bacterium as well as methods and uses thereof.

Modified gram positive bacteria and uses thereof

The present invention relates to gram positive bacteria with increased stress resistance and/or improved storage characteristics. In particular, the invention relates to gram positive bacterium which accumulate intracellular trehalose. The gram positive bacterium according to the invention lack cellobiose-specific PTS system IIC component (PtcC)activity. The gram positive bacterium may further lack trehalose 6-phosphate phosphorylase (TrePP)activity. The gram positive bacterium may further overexpress trehalose transporters. The invention further relates to compositions comprising such gram positive bacterium as well as methods and uses thereof.

The present invention relates to a gram positive bacterium, preferably a lactic acid bacterium (LAB) or, with increased stress resistance and/or improved manufacturing, processing and/or storage characteristics. In particular, the invention relates to a gram positive bacterium which accumulate intracellular trehalose. The gram positive bacterium according to the invention lack trehalose 6-phosphate phosphorylase (TrePP) activity. The gram positive bacterium may further lack cellobiose-specific PTS system IIC component (ptcC) activity. The gram positive bacterium may further overexpress trehalose transporters. The invention further relates to compositions comprising such gram positive bacterium as well as methods and uses thereof.

Treatments for chronic enterocolitis are disclosed. More specifically, methods for administration of pharmaceutical compositions that include anti-TNF-alpha antibody producing lactic acid microorganisms, such assp. andsp., are disclosed for the treatment of chronic enterocolitis.

Anti-TNF alpha producing lactic acid bacteria for the treatment of chronic enterocolitis

The invention is in the field of molecular biology, and relates to recombinant engineering and protein expression. More in particular, the invention relates to nucleic acids for recombinant expression of proteins comprising sequences derived fromand useful as promoters. The invention further relates to vectors comprising the nucleic acids and host cells transformed therewith. The invention also covers the use of host cells comprising the nucleic acids or vectors for expressing heterologous or homologous proteins; and also for delivery, especially therapeutic delivery, of the said proteins to subjects.

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De Pinte, Belgium

Klaas Vandenbroucke