Development of novel antimicrobial substances and the detailed understanding of their mechanisms of action are of high priority tasks, because of the persistent evolution of resistance towards antibiotics. Recently, antibiotic-resistant strains showed highly attracting susceptibility profiles to antimicrobial peptides (AMPs); a high frequency of collateral sensitivity was observed, whereas occurrence of cross-resistance was relatively rare. An intriguing manifestation of the potential advantageous drug interactions is the sub-MIC synergy between a membrane targeting AMPs and antibiotics. We found that a membrane targeting AMP sequence PGLa derivative caused 30-fold decrease in resistance level of resistant bacteria as adjuvant at subinhibitory concentrations. Chemogenetic findings and the literature observations implying a potential pore-free transport phenomenon strongly focused our attention on the electrolyte equilibrium and transport across the bacterial membrane, and the possible ways through the AMP sequences can affect these parameters.

Selected publications

Rationally Designed Foldameric Adjuvants Enhance Antibiotic Efficacy: Via Promoting Membrane Hyperpolarization. Bhaumik, K. N.; Hetényi, A.; Olajos, G.; Martins, A.; Spohn, R.; Németh, L.; Jojart, B.; Szili, P.; Dunai, A.; Jangir, P. K.; Daruka, L.; Földesi, I.; Kata, D.; Pál, C.; Martinek, T. A. Mol. Syst. Des. Eng. 2022, 7 (1), 21–33.

Rapid Evolution of Reduced Susceptibility against a Balanced Dual-Targeting Antibiotic through Stepping-Stone Mutations. Szili, P.; Draskovits, G.; Révész, T.; Bogár, F.; Balogh, D.; Martinek, T.; Daruka, L.; Spohn, R.; Vásárhelyi, B. M.; Czikkely, M.; Kintses, B.; Grézal, G.; Ferenc, G.; Pál, C.; Nyerges, Á. Antimicrob. Agents Chemother. 2019, 63 (9).

Antibiotic-Resistant Bacteria Show Widespread Collateral Sensitivity to Antimicrobial Peptides. Lázár, V.; Martins, A.; Spohn, R.; Daruka, L.; Grézal, G.; Fekete, G.; Számel, M.; Jangir, P. K.; Kintses, B.; Csörgo, B.; Nyerges, Á.; Györkei, Á.; Kincses, A.; Dér, A.; Walter, F. R.; Deli, M. A.; Urbán, E.; Hegedus, Z.; Olajos, G.; Méhi, O.; Bálint, B.; Nagy, I.; Martinek, T. A.; Papp, B.; Pál, C. Nat. Microbiol. 2018, 3 (6), 718–731.