Researchers from the Moscow Institute of Physics and Technology (MIPT) and Moscow State University have demonstrated that derivatives of triphenylphosphonium can function as antibiotics capable of targeting a cell-damaging pathogen. In future work, these compounds hold promise for treating dangerous bacterial diseases such as tuberculosis and staphylococcal infections. The findings were communicated to socialbites.ca by the Russian Ministry of Education and Science, highlighting a potential shift in how bacterial infections may be combated.
One ongoing challenge in antimicrobial development is identifying drugs that attack bacteria while sparing the host’s nuclear cells. Experts see potential in drugs built around protonophores, molecules that move protons across membranes driven by existing membrane potential. Among these, triphenylphosphonium stands out as a notable example due to its distinctive interactions with cellular membranes.
In human cells, the typical membrane potential is around -60 millivolts, whereas bacterial cells commonly exhibit a stronger negative charge near -180 millivolts. This difference creates a favorable environment for positively charged phosphonium derivatives to accumulate in bacterial cells, enabling selective action with reduced risk to human tissues.
Triphenylphosphonium derivatives are widely used as delivery vehicles for antibiotics, guiding therapeutic compounds to infection sites and supporting recovery. Historically, their clinical use has been limited by concerns about toxicity. The latest work from Russian researchers demonstrates a strategy that minimizes harm to healthy cells while effectively targeting bacterial cells, potentially broadening the range of feasible applications.
As explained by Pavel Nazarov, Associate Professor at the Training Programs Center of the Phystech School of Biological and Medical Physics at Belozersky Moscow State University, triphenylphosphonium derivatives can exert negative effects on bacterial cells while sparing general body tissues when they reach certain organs such as the liver. This selective behavior opens possibilities for targeted antibacterial therapies where the compounds concentrate in infected areas and reduce bacterial viability without compromising overall cellular health.
The mechanism involves slowing key processes inside bacterial cells. The derivatives hinder cell division, disrupt protein synthesis, and limit energy production by interfering with antioxidant activity. This multi-pronged disruption weakens bacteria and can lead to the clearance of infections that are particularly challenging to treat, including drug-resistant strains. The research points toward the potential development of new antibiotics capable of countering even the most dangerous infections with a favorable safety profile for the host.
In practical terms, the approach may translate into treatments that deliver robust antibacterial effects in organs prone to infection, while reducing systemic toxicity. The concept relies on exploiting the membrane potential differences between human and bacterial cells to achieve selective uptake. If validated through further studies and clinical trials, such strategies could complement existing antibiotics and reduce treatment durations for severe bacterial diseases while sparing healthy tissues from collateral damage.