New molecules can offer breakthrough in fight against antibiotic resistance

In a new study, researchers show how so‑called TriPcides can target the bacterium Staphylococcus aureus, including antibiotic‑resistant strains such as MRSA. The compounds disrupt the bacteria’s ability to cause infection and can also kill dormant bacterial cells, which are often difficult to treat with existing antibiotics.

“We have developed an entirely new class of compounds with very promising antibacterial properties. What stands out is that the bacteria we have studied do not easily develop resistance to these synthetic antibiotics. We have also not observed any existing resistance in a wide range of clinical isolates, which is encouraging” says Fredrik Almqvist, Professor at the Department of Chemistry at Umeå University.

Antibiotic resistance is widely recognised as a growing global threat to public health. As bacteria become resistant to existing drugs, the risk increases of infections that are difficult to treat, longer hospital stays and higher mortality rates. There is therefore an urgent need for new strategies that can complement or replace current antibiotics.

The new compounds act by affecting bacterial cell membranes and interfering with processes that are essential for establishing infection. In laboratory studies, they have shown activity against several Gram‑positive bacteria, including resistant strains.

An important finding is that the compounds are also effective against so‑called persister cell – bacteria in a dormant state that often survive antibiotic treatment. These cells can later cause a relapse of the infection.

“Persister cells are bacteria that enter a state similar to dormancy, in which they do not divide and are metabolically inactive. A small fraction of the bacteria causing an infection are in this state and can therefore survive antibiotic treatment. Once treatment ends, they can resume growth and cause the infection to return. Our TriPcides also showed activity against persister cells, which is very exciting” says Fredrik Almqvist.

The discovery could, in the longer term, contribute to new treatment approaches for severe infections, although further research is required before the findings can be applied clinically.

In addition to antibiotic resistance, the findings are also relevant to another societal challenge: the strain on healthcare systems. More effective treatments could reduce the need for care and free up resources, particularly in cases where infections currently require prolonged treatment and repeated interventions.

“This study is the first to investigate this new type of antibiotic and offers hope that we can continue developing effective new treatments. There is a significant global need for new types of antibiotics to which bacteria have not already developed resistance, and this discovery is a positive step forward. We may be moving towards a new and effective option for combating infectious diseases” says Fredrik Almqvist.

The study is based on an international collaboration. Three research groups at Umeå University contributed, and the Umeå Centre for Microbial Research (UCMR) played an important role in bringing together complementary expertise.

The study has been published in the scientific journal Science Advances.

About the scientific article

Hasan Tükenmez, Taylor M. Nye, Pardeep Singh, Aaron Mychack, Mari Bonde, Suzanne Hickerson, Chloe L. P. Obernuefemann, Jerome S. Pinkner, Shaochun Zhu, Souvik Sarkar, Jaideep B. Bharate, Ingeborg van der Lingen, Anh Quoc Ntuyenm, V. U. Bhaskara Rao, Anders E. G. Lindgren, Hanna Klein, Zongsen Zou, Karen W. Dodson, Suzanne Walker, Andre Mateus, Jörgen Johansson, Michael G. Caparon, Fredrik Almqvist, Scott J. Hultgren, Tunable TriPcides suppress virulence factor secretion during Staphylococcus aureus infection and kill dormant cells, Science Advances VOL. 12, NO. 19, DOI: 10.1126/sciadv.aec9100