Altering microbial populations and modifying microbiota
The invention relates to methods, uses, systems, arrays, engineered nucleotide sequences and vectors for inhibiting bacterial population growth or for altering the relative ratio of sub-populations of first and second bacteria in a mixed population of bacteria. The invention is particularly useful, for example, for treatment of microbes such as for environmental, medical, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system.
1. A method for treating an infection caused by bacterial or archaeal host cells in an organism, the method comprising:
(a) contacting the host cells with an engineered nucleic acid for producing a host modifying crRNA (HM-crRNA), and
(b) producing the HM-crRNA in the host cells;
wherein
(i) the HM-crRNA is operable with a Type I Cas in the host cells, wherein the engineered nucleic acid and the Type I Cas are comprised by a Type I HM-CRISPR/Cas system in the host cells;
(ii) the HM-crRNA comprises a nucleotide sequence that is capable of hybridizing to the target sequence in the host cells to guide the Type I Cas to modify the target sequence in the host cells; and
(iii) wherein the Type I Cas is an endogenous Cas in the host cells;
wherein the target sequence is modified by the Type I HM-CRISPR/Cas system and the infection is treated.
2. The method of claim 1 , wherein the method limits spread of the infection in the organism.
3. The method of claim 1 , wherein the host cells are killed or growth of the host cells is inhibited.
4. The method of claim 1 , wherein the engineered nucleic acid for producing the HM-crRNA is present in a phage, phagemid or plasmid.
5. The method of claim 1 , wherein the target sequence is a host target sequence.
6. The method of claim 1 , wherein the host cells are C. difficile, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Salmonella enterica, Acinetobacter baumannii , or Staphylococcus aureus cells.
7. The method of claim 1 , wherein the method is for medical, dental or ophthalmic use.
8. The method of claim 1 , wherein the organism is a plant.
9. The method of claim 8 , wherein the organism is a crop.
10. The method of claim 1 , wherein the organism is an animal.
11. The method of claim 10 , wherein the organism is a human.
12. The method of claim 11 , wherein the host cells are present in a human microbiota.
13. The method of claim 1 , wherein host cells are killed and the infection is treated or the spread of infection is limited, wherein the method is for medical, dental or ophthalmic use, and the organism is an animal or a human.
14. The method of claim 1 , wherein host cells are killed and the infection is treated or the spread of infection is limited, wherein the method is for environmental or agricultural use, and the organism is a plant.
15. The method of claim 13 , wherein the host cells are C. difficile, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Salmonella enterica, Acinetobacter baumannii , or Staphylococcus aureus cells.
16. The method of claim 14 , wherein the host cells are C. difficile, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Salmonella enterica, Acinetobacter baumannii , or Staphylococcus aureus cells.
17. The method of claim 1 , wherein the engineered nucleic acid for producing the HM-crRNA is present in a phagemid.
18. The method of claim 1 , wherein the engineered nucleic acid for producing the HM-crRNA is present in a phage.
19. The method of claim 1 , wherein the engineered nucleic acid for producing the HM-crRNA is present in a plasmid.
20. The method of claim 1 , wherein the host cells are present in a mixed population of bacteria, wherein the mixed population comprises a first bacterial sub-population and a second bacterial sub-population, wherein the first bacterial sub-population comprises a first bacterial species and the second bacterial sub-population comprises the host cells, wherein the host cells are of a second bacterial species, wherein the second bacterial species is a different species than the first bacterial species, and wherein the HM-crRNA does not target the first bacterial species, and wherein the mixed population of bacteria is present in a microbiota.
21. The method of claim 13 , wherein the host cells are present in a mixed population of bacteria, wherein the mixed population comprises a first bacterial sub-population and a second bacterial sub-population, wherein the first bacterial sub-population comprises a first bacterial species and the second bacterial sub-population comprises the host cells, wherein the host cells are of a second bacterial species, wherein the second bacterial species is a different species than the first bacterial species, and wherein the HM-crRNA does not target the first bacterial species, and wherein the mixed population of bacteria is present in a microbiota.
22. The method of claim 14 , wherein the host cells are present in a mixed population of bacteria, wherein the mixed population comprises a first bacterial sub-population and a second bacterial sub-population, wherein the first bacterial sub-population comprises a first bacterial species and the second bacterial sub-population comprises the host cells, wherein the host cells are of a second bacterial species, wherein the second bacterial species is a different species than the first bacterial species, and wherein the HM-crRNA does not target the first bacterial species, and wherein the mixed population of bacteria is present in a microbiota.
23. The method of claim 1 , wherein the host cells are Clostridium, Pseudomonas, Klebsiella, Salmonella, Acinetobacter , or Staphylococcus cells.