Characteristics and resistance of tachyplesin-I resistance in Pseudomonas aeruginosa

Abstract:

[Objective] To explore the safety of tachyplesin I as an antibacterial drug for wide clinical application, we induced Pseudomonas aeruginosa resistance to tachyplesin I and studied the preliminary resistance mechanisms, which may provide theoretical basis for the widely application of tachyplesin-I.[Methods] First, we induced P. aeruginosa resistance to tachyplesin I using continuously increasing concentration selection pressure and monitored bacterial resistance. Second, we studied the stability, cross-resistance and cost of resistance of resistant strain. Last, we investigated the potential role of extracellular proteases, extracellular polysaccharide content and biofilm formation in the resistance mechanism.[Results] After more than 30 serial transfers in P. aeruginosa ATCC27853 under increasing concentrations of tachyplesin I selection, the MICvalues for P. aeruginosa was gradually increased, whereas high resistance to tachyplesin I was produced until 80 serial transfers. P. aeruginosa ATCC27853 showed resistance to tachyplesin I under long-term, continuously increasing concentration selection pressure. Cross-resistances between tachyplesin I, amikacin and other antimicrobial peptides (pexiganan, tachyplesin Ⅲ, and polyphemusin I) were observed in resistant mutant. Our resistant strain displayed a substantial cost of resistance mainly in the form of a much longer lag phase in the absence of tachyplesin I in P. aeruginosa, whereas in the presence of tachyplesin I, resistant strain had a shorter lag phase and greater growth rate. The resistant strain P. aeruginosa ATCC27853-88-2 exhibited increased levels of extracellular proteolytic activity and reduced the antimicrobial activity of tachyplesin I. Under the same conditions, extracellular polysaccharide content of the resistant strain was higher, more easily to form biofilm than the original strain.[Conclusion] We demonstrate that long-term continuous exposure to high concentrations of tachyplesin I can induce resistance in P. aeruginosa ATCC27853 and the potential involvement of extracellular protease and biofilm formation in mediating this resistance.