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

ABSTRACT A total of 50 engineered strains with various resistance mechanisms from two fully susceptible strains, Acinetobacter baumannii KAB1544 and ATCC 17978, were constructed by in-frame deletion, site-directed mutagenesis and plasmid transformation. These strains included 31 strains with chromosome-mediated resistance and 19 strains with plasmid-mediated resistance, and each of the 50 resistance mechanisms showed similar effects on the MICs for KAB1544 and ATCC 17978. Compared to the parental strains, the engineered strains related to some efflux pumps showed a significant (≥4-fold) difference in the MICs of β-lactams, quinolones, aminoglycosides, tetracyclines, folate pathway inhibitors and/or phenicols, while no significant (≥4-fold) effects on the MICs were found for the engineered strains lacking OmpA, CarO, Omp25, Omp33, OmpW or OprD. Mechanisms due to GyrA/ParC mutations, β-lactamase, aminoglycoside-modifying enzyme, 16S rRNA methylase and tet resistance gene 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 the drug development against superbugs.