Tuesday, 7 February 2017

microbiology - Could plasmids and conjugation mechanisms be used against antibiotic-resistant bacteria?



I'm surprised no one has mentioned something like this.


Plasmids are often exchanged between bacteria, sometimes through conjugation. In particular, conjugation could be considered an "open-port" vulnerability.


Intuitively, there are several schemes that exploit plasmids and bacterial conjugation that could form alternatives to antibiotics:



A specially engineered nanoscale capsule or specially rigged bacterial cell is programmed to call out to target bacteria for conjugation. When the conjugation tunnel is opened, the capsule or rigged bacterial cell floods the target bacterium with toxins or malicious RNA designed to sabotage it.



A specially designed novel antibiotic contains a conjugation-signaling structure. When a bacterium docks with the antibiotic molecule, the antibiotic irreversibly latches on and tears a massive hole in the bacterium from the inside.




Plasmids that confer significant advantages are isolated from naturally-occuring bacteria and a special "crash gene" is added to the plasmids. The modified plasmids are implanted back into bacteria that are known to spread them around.


The crash gene's promoter listens for a small set of chemical cues. If it detects a certain threshold of 1 of these cues, it becomes active and sabotages the bacterium. The gene could code for a toxin that specifically damages bacteria. Alternately the promoter could be specifically designed so it never releases the chemical cue, forcing the bacterium to repeatedly produce a garbage produce and waste its resources.



This might be more difficult to build. A synthetic plasmid encodes 2 products: The first confers a significant benefit to prevent bacteria from discontinuing it through natural selection. The other product is periodically ("randomly") transcribed and vandalizes other plasmids, causing large numbers of nonsense mutations. A set of special markers on the synthetic plasmid protects it from vandalism by its own product. This could silently remove antibiotic resistance from bacterial populations and the bacteria have no way of "knowing" they've been sabotaged until it's too late.




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