Question

Targeting the resistance genes specifically could be a potential solution

According to this study from NCBI, the two separate resistant strains of Y. pestis in Madagascar was not an isolated phenomenon, and could indicate a serious threat to public health. There is concern that another fatal plague epidemic is a very serious possibility and our current methods of treatment with antibiotics will not be effective. It is interesting to me that the resistant strains carry the resistance genes on the same plasmid that was likely acquired via conjugation. Would it be possible to attack this gene specifically through various gene therapy techniques instead of treating the pathogen via broad- or narrow-spectrum bactericidal antibiotics?

Answer 1

Answer: Conjugation is a method of sexual reproduction in bacteria where bacteria carrying F plasmid (fertility factor) transfer the genetic material to bacteria without F factor (F^- bacteria) by forming physical contact via pili. Since bacteriocidal antibiotics are not always an option all the time as they kill all the bacteria without specificity, it is required to target the bacteria to stop transfering the resistant gene to prevent the fatal outcome.

To this end, we should target the molecule playing key role in conjugation and inhibit that. DNA relaxase are the key protein of the conjugation process. TraI is an example of DNA relaxase of F-plasmid. TraI makes complexes with certain molecules that acts as potent cell inhibitor which selectively kills cells capable of conjugation. Two clinically approved inhibitors are Clodronate and Etidronate. They specifially kills the conjugating cells and hence this way we can avoid using bacteriocidal antibiotics (Scott A. Lujan, 2008).

Other methods include CRISPRs, development of restriction systems that digest the F plasmid once it enters the recepient cell, creating incompatibility between F⁺ and F^- cells.

Reference:

Lujan. S. A. 2008. Bacterial Conjugation and its Inhibition: The Hows and Whys of Conjugation and What Can be Done to Control It.