Abstract：
:The rapid emergence of extensively drug-resistant A. baumannii has posed a major threat to global public health, emphasizing the desperate need for novel therapeutic strategies. We report the development of a highly efficient genome-engineering platform in A. baumannii by coupling a Cas9 nuclease-mediated genome cleavage system with the RecAb recombination system. We applied the CRISPR-Cas9/RecAb system to dissect the oxidative stress-sensing mechanism of OxyR by performing alanine scanning mutagenesis of 13 residues residing in the H2O2-sensing pocket, pinpointing new vital factors for H2O2 sensing. Moreover, we developed a cytidine base-editing system, enabling programmed C to T conversions. Exploiting this powerful technique, we systematically investigated the drug-resistant mechanisms in a clinically isolated multidrug-resistant A. baumannii strain by generating premature stop codons in the possible resistance genes, unveiling distinct roles of these genes in drug resistance. The development of these genome-engineering methods will facilitate new therapeutic-means development in A. baumannii and related organisms.
journal_name
Cell Chem Bioljournal_title
Cell chemical biologyauthors
Wang Y,Wang Z,Chen Y,Hua X,Yu Y,Ji Qdoi
10.1016/j.chembiol.2019.09.003subject
Has Abstractpub_date
2019-12-19 00:00:00pages
1732-1742.e5issue
12eissn
2451-9456issn
2451-9448pii
S2451-9456(19)30277-6journal_volume
26pub_type
杂志文章abstract：:Because small-molecule activators of adenylyl cyclases (AC) affect ACs cell-wide, it is challenging to explore the signaling consequences of AC activity emanating from specific intracellular compartments. We explored this issue using a series of engineered, optogenetic, spatially restricted, photoactivable adenylyl cy...
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