Competence-inhibiting drugs may prevent the spread of antibiotic resistance

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A study, recently published in Cell Host and Microbe, has suggested that some approved drugs may be able to prevent bacterial competence, inhibiting the incorporation of free DNA into the genome and mitigating the risk of acquiring antibiotic-resistance genes.

The research, which was carried out by teams from the University of Groningen (Netherlands) and the University of Lausanne (Switzerland) in partnership with Heidelberg University (Germany), aimed to elucidate the underpinnings of the process that makes bacterial cells competent and how to prevent it.

“We collaborated with scientists from Heidelberg , who developed a high-throughput assay to simultaneously test cells for competence and growth” explained author Arnau Domenech (University of Lausanne).

Forty-six drugs were identified by a high-throughput screening of 1366 already approved compounds. These drugs not only prevented the induction of bacterial competence but also did not negatively impact bacterial growth.

“When cells are under growth stress, for instance in the presence of antibiotics, they try to find a solution and become resistant to these drugs,” stated Domenech. “Importantly, we did not observe resistance to the drugs found here as they do not cause growth stress.”

The 46 drugs identified were classified as either affecting ion homeostasis or antipsychotics, although both classes of drugs disrupt proton-motive force. The disturbance in electrochemical gradient inhibits genetic transformation by preventing quorum sensing, as the secretion of the peptide, CSP, is blocked.

“In the lab, we observed that our competence-blocking drugs could prevent the transfer of antibiotic-resistance genes to susceptible strains of Streptococcus pneumoniae and we obtained the same results in cultures of human lung epithelial cells,” commented Domenech.

These drugs also prevented the transmission of bacterial resistance genes in a mouse model of infection.

As human cells also utilize proton-motive force, future research is needed to determine if these types of drugs are safe to use in humans. However, this study has highlighted a pathway that could be targeted to prevent bacteria from acquiring resistance genes and it is suggested that these drugs could be potentially taken in combination with our current antibiotics to extend their lifespan.

Take a look at the author’s explanimation:

 

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Sources: Domenech A, Brochado AR, Sender V et al. Proton-motive force disruptors block bacterial competence and horizontal gene transfer. Cell Host Microbe (2020); www.eurekalert.org/emb_releases/2020-03/uog-adc022820.php

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