Sapanlika Swarnamali Baththana Madiyanselage, Ph.D.
von Lintig lab
Sora Jin, Ph.D.
Meinan Lyu, Ph.D.
Neisseria gonorrhoeae is a human-specific pathogen that causes the sexually transmitted infection gonorrhea. This pathogen has emerged as one of the most highly antibiotic-resistant Gram-negative bacteria. Multidrug efflux is a major mechanism that N. gonorrhoeae uses to counteract the action of multiple classes of antibiotics. The most predominant multidrug efflux pump is the MtrD membrane protein, which belongs to the hydrophobic and amphiphilic efflux resistance-nodulation-cell division (HAE-RND) family and confers resistance to a variety of structurally unrelated toxic compounds. We focus on solving the structures of MtrD and multidrug bound complexes by using cryo-EM, revealing how this membrane protein mediates resistance to various antibiotics.
Chris E. Morgan, Ph.D.
Mitchell Moseng, Ph.D.
Wilnelly Hernandez-Sanchez, Ph.D.
Since DNA replication mechanisms are unable to extend the extreme ends of the lagging strand, a portion of genetic material is lost during each cell division. To compensate for this loss, the ends of all linear chromosomes contain repetitive DNA sequences called telomeres. A specialized enzyme called telomerase is responsible for the synthesis of telomere DNA and is essential for the retention of genomic material during continuous cellular division. Alterations to telomerase genes are associated with a range of diseases, including cancer, dyskeratosis congenita, aplastic anemia, and idiopathic pulmonary fibrosis. Whereas telomerase activity is undetectable in healthy adult somatic cells, it is upregulated in 90% of all metastatic tumor cells, allowing cancer cells to proliferate indefinitely by avoiding senescence. Because of the selective expression of telomerase in cancer cells, telomerase is a well-recognized cancer target. Thus, cancer researchers must understand the fundamental and molecular processes related to telomerase enzymology in healthy and diseased states. Insights from the findings in this study could guide new mechanisms for the therapeutic regulation of telomerase function.
Vikas Hazarilal Sharma, Ph.D.
Kyle Whiddon, Ph.D.
Zhemin Zhang, Ph.D.
Acinetobacter baumannii is a Gram-negative, nonfermentative bacillus, which is considered as an important nosocomial pathogen causing pneumonia, urinary tract infections, bacteremia, septicemia, and meningitis. Infected by A. baumannii is extremely difficult to cure. One major mechanism that A. baumannii uses to mediate antibiotic resistance is the expression of multidrug efflux pumps, especially those belonging to the resistance-nodulation-cell division (RND) superfamily. The most clinically relevant RND-type multidrug efflux in A. baumannii is the AdeJ membrane protein, which extrudes multiple classes of antibiotics, such as tetracyclines, aminoglycosides, β-lactams, and fluoroquinolones. However, the substrate recognition mechanism of AdeJ is still unknown. Thus, an atomic level structure of A. baumannii AdeJ multidrug efflux pump bound with substrate complex will be the key point to reveal a mechanism on how AdeJ recognize and extrude the antibiotics. These data in the project will provide an essential structural foundation for future anti-bacterial drug discovery.