Compositions and methods for regulating bacterial pathogenesis
View Patent ↗The production of a purified extracellular bacterial signal called autoinducer-2 is regulated by changes in environmental conditions associated with a shift from a free-living existence to a colonizing or pathogenic existence in a host organism. Autoinducer-2 stimulates LuxQ luminescence genes, and is believed also to stimulate a variety of pathogenesis related genes in the bacterial species that produce it. A new class of bacterial genes is involved in the biosynthesis of autoinducer-2.
1. An isolated gram negative bacterial strain comprising a first genetic alteration introduced into a nucleotide sequence from the group consisting of SEQ ID NOS:1-9, wherein the first genetic alteration is in the luxS gene and inhibits production of functional LuxS protein, inhibiting production of the autoinducer-2 having the structure of the autoinducer-2 produced by Vibrio harveyi , and a second genetic alteration that inhibits the ability to detect an acyl-homoserine lactone autoinducer.
2. The isolated bacterial strain of claim 1 , wherein the strain is a V. harveyi strain.
3. The isolated bacterial strain of claim 1 , wherein the first genetic alteration in the luxS gene inhibits production of a pentanedione.
4. The isolated bacterial strain of claim 3 , wherein the pentanedione is 4,5-dihydroxy-2,3-pentanedione.
5. The isolated bacterial strain of claim 1 selected from the group consisting of Salmonella typhimurium and Escherichia coli.
6. The isolated bacterial strain of claim 1 selected from the group consisting of Haemophilus influenzae, Helicobacter pylori, Borrelia burgdorferi , and Vibrio cholerae.
7. The isolated bacterial strain of claim 1 selected from the group consisting of Haemophilus influenzae, Helicobacter pylori, Borrelia burgdorferi, Neisseria meningitidis, Neisseria gonorrhoeae, Yersinia pestis, Campylobacter jejuni , and Vibrio cholerae.
8. The isolated bacterial strain of claim 1 , wherein the strain comprises a luxN gene, and wherein the second genetic alteration is in the luxN gene.
9. The isolated bacterial strain of claim 1 , wherein the acyl-homoserine lactone is N-(3 -hydroxybutanoyl)-L-homoserine lactone.
10. A kit comprising the isolated bacterial strain of claim 1 .
11. The kit of claim 10 , wherein the strain is a V. harveyi strain.
12. The kit of claim 10 , wherein the first genetic alteration in the luxS gene inhibits production of a pentanedione.
13. The kit of claim 12 , wherein the pentanedione is 4,5-dihydroxy-2,3-pentanedione.
14. The kit of claim 10 , wherein the bacterial strain is selected from the group consisting of Salmonella typhimurium and Escherichia coli.
15. The kit of claim 10 , wherein the bacterial strain is selected from the group consisting of Haemophilus influenzae, Helicobacter pylon, , Borrelia burgdorferi , and Vibrio cholerae.
16. The kit of claim 10 , wherein the bacterial strain is selected from the group consisting of Haemophilus influenzae, Helicobacter pylori, Borrelia burgdorferi, Neisseria meningitidis, Neisseria gonorrhoeae, Yersinia pestis, Campylobacter jejuni , and Vibrio cholerae.
17. The kit of claim 10 , wherein the strain comprises a luxN gene, and wherein the second genetic alteration is in the luxN gene.
18. The kit of claim 10 , wherein the acyl-homoserine lactone is N-(3-hydroxybutanoyl)-L-homoserine lactone.