Recombinant bacteria and uses thereof
The present disclosure provides a recombinant, probiotic lactic acid bacterium, wherein the bacterium comprises a non-replicating plasmid vector comprising (a) a tumor suppressor gene or anti-inflammatory gene operably linked to a first promoter that directs expression of the tumor suppressor gene or anti-inflammatory gene in a mammalian cell, and (b) an adhesin gene operably linked to a second promoter that directs expression of the adhesin gene in the bacterium. The present disclosure also provides uses of the recombinant bacterium, and methods of constructing the recombinant bacterium. The present disclosure also provides a method of treating cancer in a subject, wherein the method comprises administering a pharmaceutically effective amount of a recombinant, probiotic lactic acid bacterium, wherein the bacterium comprises a non-replicating plasmid vector comprising an adhesin gene operably linked to a promoter that directs expression of the adhesin gene in the bacterium.
1 . A method of treating a gastrointestinal cancer in a subject in need thereof, wherein the method comprises administering a pharmaceutically effective amount of a recombinant, probiotic lactic acid bacterium into the gastrointestinal tract of the subject, wherein the bacterium comprises a non-replicating plasmid vector comprising
(a) a tumor suppressor gene operably linked to a first promoter that directs expression of the tumor suppressor gene in a mammalian cell, wherein the first promoter is a mammalian promoter, and wherein the tumor suppressor gene is DUSP10, and
(b) an adhesin gene operably linked to a second promoter that directs expression of the adhesin gene in the bacterium, wherein the second promoter is a prokaryotic promoter, and wherein the adhesin is fibronectin-binding protein.
2 . The method of claim 1 , wherein the bacterium is a lactic-acid producing bacterium.
3 . The method of claim 2 , wherein the bacterium is of the Lactococcus genus.
4 . The method of claim 3 , wherein the bacterium is Lactococcus lactis.
5 . The method of claim 1 , wherein the method further comprises administering a pharmaceutically effective amount of immune checkpoint inhibitor, optionally wherein the immune checkpoint inhibitor is anti-programmed death ligand-1 (PDL-1).
6 . The method of claim 1 , wherein the cancer is selected from the group consisting of esophageal cancer, gastric cancer, colorectal cancer and anal cancer.
7 . The method of claim 6 , wherein the cancer is colorectal cancer.
8 . The method of claim 1 , wherein the method reduces inflammation of the esophagus, the stomach, the small intestine, the caecum, the large intestine, or the anus.
9 . The method of claim 1 , wherein the recombinant, probiotic lactic acid bacterium is administered orally.
10 . The method of claim 1 , wherein the subject is a human.