title: Experimental Induction of Bacterial Resistance to the Antimicrobial Peptide Tachyplesin I and Investigation of the Resistance Mechanisms.
abstract: Tachyplesin I is a 17-amino-acid cationic antimicrobial peptide (AMP) with a typical cyclic antiparallel β-sheet structure that is a promising therapeutic for infections, tumors, and viruses. To date, no bacterial resistance to tachyplesin I has been reported. To explore the safety of tachyplesin I as an antibacterial drug for wide clinical application, we experimentally induced bacterial resistance to tachyplesin I by using two selection procedures and studied the preliminary resistance mechanisms. Aeromonas hydrophila XS91-4-1, Pseudomonas aeruginosa CGMCC1.2620, and Escherichia coli ATCC 25922 and F41 showed resistance to tachyplesin I under long-term selection pressure with continuously increasing concentrations of tachyplesin I. In addition, P. aeruginosa and E. coli exhibited resistance to tachyplesin I under UV mutagenesis selection conditions. Cell growth and colony morphology were slightly different between control strains and strains with induced resistance. Cross-resistance to tachyplesin I and antimicrobial agents (cefoperazone and amikacin) or other AMPs (pexiganan, tachyplesin III, and polyphemusin I) was observed in some resistant mutants. Previous studies showed that extracellular protease-mediated degradation of AMPs induced bacterial resistance to AMPs. Our results indicated that the resistance mechanism of P. aeruginosa was not entirely dependent on extracellular proteolytic degradation of tachyplesin I; however, tachyplesin I could induce increased proteolytic activity in P. aeruginosa Most importantly, our findings raise serious concerns about the long-term risks associated with the development and clinical use of tachyplesin I.
authors.affiliation: College of Life Science and Engineering, Henan University of Urban Construction, Ping Dingshan, People's Republic of China hongjun@hncj.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Hong
authors.affiliation: College of Life Science and Engineering, Henan University of Urban Construction, Ping Dingshan, People's Republic of China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Hu
authors.affiliation: College of Life Science and Engineering, Henan University of Urban Construction, Ping Dingshan, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ke
mesh_terms: D016980:Aeromonas hydrophila / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects / Q000648:ultrastructure; D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002438:Cefoperazone / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010456:Peptides, Cyclic / Q000494:pharmacology*; D059748:Proteolysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects / Q000648:ultrastructure; D012641:Selection, Genetic; D014466:Ultraviolet Rays
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D010456:Peptides, Cyclic; C057636:tachyplesin peptide, Tachypleus tridentatus; C062385:polyphemusin I; D002438:Cefoperazone; D000583:Amikacin; C093828:pexiganan