Liping Li

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Current work

Due to its highly multidrug-resistant nature, Acinetobacter baumannii has become a very problematic hospital-acquired human pathogen for clinicians worldwide, especially in intensive care units.

So far, there are three major drug resistance mechanisms indentified in this organism: 1) antibiotic inactivation, through which enzymes produced by bacteria can degrade or inactivate antibiotics; 2) target structure reprogramming, where targets are modified so that they are no longer recognized by antibiotics; 3) drug efflux pumps, which are membrane transporter proteins, and when over-expressed, can export drugs against their concentration gradient to reduce intracellular drug concentration significantly.

However, bacteria respond to drug threats through not only a single mechanism but a tightly regulated network. One of my projects involves studying local and global transcriptional regulation of multidrug resistance mechanisms in A. baumannii. I will apply techniques such as random mutagenesis, transposon-directed insertion-site sequencing (TraDIS), saturation mutagenesis (TargeTron system) to find novel transcriptional regulators, and series of classical biomolecular technologies in characterizing regulation mechanisms. In addition, these studies 1) will complement substrate specificity study for their membrane effluxome counterparts which are notorious in purification and crystallization, and 2) may get insight into the physiological role of membrane transporters, not only drug resistant.

It is hypothesized that membrane drug effluxome may have other underlying physiological function, while their drug resistant capacity only evolved afterwards. My other project is aiming to analyse the effect of environmental compounds on those transporters in A. baumannii by qRT-PCR, and screening E.coli clones with over-expressed A. baumannii drug transporters by environmental compounds as well, to see whether they do have other cellular roles.

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