Avaliação da atividade antimicrobiana in vitro do peptídeo paje em isolados clínicos de acinetobacter baumannii resistentes aos carbapenêmicos.

Abstract

Antimicrobial resistance is a threat to global public health. Acinetobacter baumannii is an important agent of healthcare-associated infections. Considering the lack of new antimicrobials, peptides such as PAJE, developed by the combination of Papiliocin and Jellein-I, have emerged as a promising alternative against antimicrobial resistance. This study aimed to evaluate the antimicrobial activity of PAJE in clinical isolates of carbapenem-resistant A.baumannii (CRAB). Microbiological assays with PAJE were performed and MIC and MBC of 4 µg/mL were observed. The peptide promoted lysis of the bacterial cells, evident at a wavelength of 260nm. Treating the bacterial inoculum of A. baumannii for a period of 1 hour with half the MIC value (½ MIC) was able to reduce the MIC of amikacin by 32 times. In forming biofilms, PAJE reduced formation, limiting growth by 11%. In pre-established biofilms, PAJE reduced the 24-hour biofilm by approximately 77%. In the synergism test, PAJE showed an additive effect with conventional antimicrobials. The peptide was stable in different pH conditions, at different concentrations of human serum, fetal bovine serum, serum albumin and in the presence of NaCl. Only in the presence of trypsin MIC was increased. PAJE showed a bactericidal effect against logarithmically growing A. baumannii cells, completely eliminating the bacterial load after 30 minutes' exposure to the peptide at concentrations of 5X and 10X the MIC. In the resistance test, opposite to what is described in the literature, the MIC value increased significantly. PAJE showed an adequate haemolytic profile and negligible toxicity against VERO and HaCat cells lines, presenting great potential to be explored in the study and development of a new antimicrobial agent effective against A. baumannii isolates.