Effects of different resistance mechanisms on antimicrobial resistance in Acinetobacter baumannii: a strategic system for screening and activity testing of new antibiotics

A total of 50 engineered strains with various antimicrobial resistance mechanisms were constructed by in-frame deletion, site-directed mutagenesis and plasmid transformation from two fully-susceptible strains (Acinetobacter baumannii KAB1544 and ATCC 17978), including 31 strains with chromosomally-mediated resistance and 19 with plasmid-mediated resistance. Each of the 50 resistance mechanisms showed similar effects on the minimum inhibitory concentrations (MICs) of KAB1544 and ATCC 17978. Compared with the parental strains, the engineered strains related to some efflux pumps showed a significant (>= 4-fold) difference in the MICs of beta-lactams, quinolones, aminoglycosides, tetracyclines, folate pathway inhibitors and/or phenicols, whereas no significant effects on the MICs were found for the engineered strains lacking OmpA, CarO, Omp25, Omp33, OmpW or OprD. Mechanisms due to GyrA/ParC mutations, beta-lactamases, aminoglycoside-modifying enzymes, 16S rRNA methylases and tet resistance genes contributed their corresponding resistance, as previously published. In conclusion, strains constructed in this study have clear resistance mechanisms and can be used to screen and assess compounds against specific resistance mechanisms for treating Acinetobacter. In addition to our previously published system for Enterobacteriaceae, the combination of these two systems could increase the coverage of bacterial types for drug assessment and facilitate the selection process of new candidates in drug development against drug-resistant superbugs. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.