CRISPR Turns Infectious Bacteria Against Themselves
A CRISPR encoded plasmid that causes Salmonella bacteria to make lethal cuts to its own genome could be a promising infection treatment to replace antibiotics.
The gut microbiome is the ecosystem of the different types of bacteria that reside in the gut. Many gut infections are caused by one species of microbiome bacteria becoming much more abundant that the others, which tips the fragile population balance out of control. Salmonella is one such example; in small populations the bacteria is harmless, but as its population gets out of control it becomes a very serious infection.
As antibiotics become more ineffective cures, due to the higher prevalence of bacterial resistance, new methods are being sought after to keep bacterial infections in check. A novel method has used CRISPR/cas-9 to equip another microbiome bacteria species with the tools to eliminate Salmonella.
Conjugative plasmids are small rings of DNA that are transmitted between bacteria to pass on antibiotic resistance through the population. In this study, researchers engineered a conjugative plasmid to encode a CRISPR/cas-9 system, which was then implanted in E-coli bacterial cells. E-coli are present in healthy microbiomes and have been observed to exchange conjugative plasmids with Salmonella.
The E. coli bacteria were then introduced to Salmonella in a petri dish, where they transmitted their engineered plasmids into Salmonella cell. Once inside, the plasmids were incorporated into the Salmonella genome. However, the CRISPR/cas-9 system was encoded to make cuts at parts of the Salmonella genome that would prove fatal to the cell.
The CRISPR system was therefore able to eliminate nearly all of the Salmonella bacteria whilst leaving the E-coli bacteria intact. Using CRISPR to control infection is advantageous, as additional genes can be encoded on the plasmid to reduce or prevent Salmonella developing resistance to CRISPR damage. Using a plasmid also promotes biofilm formation, which stimulates the species of bacteria to come closer together and allow easier transformation of the CRISPR/cas-9 plasmid.