Selectable Markers for Use in Genetic Manipulation of Extensively Drug-Resistant (XDR) Acinetobacter baumannii HUMC1

MSphere
Brian M LunaBrad Spellberg

Abstract

Acinetobacter baumannii is one of the most antibiotic-resistant pathogens in clinical medicine, and extensively drug-resistant (XDR) strains are commonly isolated from infected patients. Such XDR strains are already resistant to traditional selectable genetic markers, limiting the ability to conduct pathogenesis research by genetic disruption. Optimization of selectable markers is therefore critical for the advancement of fundamental molecular biology techniques to use in these strains. We screened 23 drugs that constitute a broad array of antibiotics spanning multiple drug classes against HUMC1, a highly virulent and XDR A. baumannii clinical blood and lung isolate. HUMC1 is resistant to all clinically useful antibiotics that are reported by the clinical microbiology laboratory, except for colistin. Ethical concerns about intentionally establishing pan-resistance, including to the last-line agent, colistin, in a clinical isolate made identification of other markers desirable. We screened additional antibiotics that are in clinical use and those that are useful only in a lab setting to identify selectable markers that were effective at selecting for transformants in vitro. We show that supraphysiological levels of tetracycline ...Continue Reading

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Citations

Jan 18, 2018·Antimicrobial Agents and Chemotherapy·Massimiliano LucidiPaolo Visca
Jan 9, 2021·Frontiers in Genetics·Ellen M E SykesAyush Kumar
Jul 30, 2019·International Journal of Biological Macromolecules·Meenakshi SharmaKrishna Mohan Poluri

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Methods Mentioned

BETA
PCR
fluorescence microscopy

Software Mentioned

BLAST
NEBuilder

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