Anti-evolution drug could stop antibiotic resistance

March 03, 2020

The spread of antibiotic resistance is partly due to the ability of bacteria to pick up DNA from their surroundings. A new study, which started at the University of Groningen, showed that drugs blocking this ability (which is called 'competence') in the bacterium Streptococcus pneumoniae can indeed stop the spread of resistance in mice. As competence is blocked without affecting cell growth, it will be difficult for the bacteria to evolve resistance to the blockade. The study was published online by the journal Cell Host & Microbe on 3 March.

The bacterium Streptococcus pneumoniae is often present in our nose or throat and is usually harmless. However, it can migrate to other parts of the body, causing severe diseases. The only way to treat these infections is with antibiotics, but with this treatment, acquisition of antibiotic resistance is a cause for concern. In order to pick up these resistance genes, a chain of events is needed that brings the bacteria in a state called 'competence'. During competence, bacteria express all the machinery required to 'catch' and incorporate the resistance genes into their own genomes.

Growth stress

In a project that started at the University of Groningen in the Netherlands and was finished at the Swiss University of Lausanne, Arnau Domenech and colleagues figured out how to stop the cells from becoming competent. 'We collaborated with scientists from Heidelberg, who developed a high-throughput assay to simultaneously test cells for competence and growth,' says Domenech. In this assay, 1366 approved drugs were screened. It turned out that 46 of them blocked the induction of competence, without negatively affecting 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,' explains Domenech. 'Importantly, we did not observe resistance to the drugs found here as they do not cause growth stress.' The 46 drugs could be divided into two groups: drugs affecting ion homeostasis, and antipsychotics. Several candidates were selected for further exploration. 'This showed that they all acted through the same mechanism,' says Domenech. They disrupted the proton-motive force: the electrochemical gradient that moves protons across the bacterial membrane and powers various processes.


'The result is that the cells fail to secrete a peptide called CSP,' explains Domenech. The CSP concentration outside the cells induces competence through a process called quorum sensing: if enough cells secrete CSP, the concentration will reach a threshold that activates competence genes.

Domenech: '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.' The drugs also reduced the transmission of bacterial resistance genes in a mouse model of infection.


The concentrations blocking the induction of competence were lower than those inhibiting growth. However, they may still not be safe to treat patients, as human cells also rely on the proton-motive force for some vital functions. 'Nevertheless, we discovered a general pathway that we can block to prevent the spread of antibiotic resistance,' says Domenech. Future studies must show whether it is feasible to use this approach in humans. If that is the case, the finding could be a breakthrough: competence blockers are anti-evolution drugs, which could be given together with antibiotics. This combination would be a very powerful weapon in the fight against infections and could extend the lifespan of current antibiotics.

An explanimation of the study can be found on YouTube:
Reference: Domenech A, Brochado AR, Sender V, Hentrich K, Henriques-Normark B, Typas A, Veening J-W. Proton-motive force disruptors block bacterial competence and horizontal gene transfer. Cell Host and Microbe 3 March 2020.

Simple science summary

Bacteria can become resistant to antibiotics by picking up resistance genes from their environment. Scientists tested a large number of known drugs for their ability to prevent bacteria from picking up foreign DNA. They found 46 candidates and discovered that they all acted through the same principle: disrupting a system that drives the secretion of a protein called CSP. In cultures of human lung cells and in mice, the drugs prevented the transfer of resistance genes to non-resistant bacteria.

University of Groningen

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to