By Nichollas Scott, CBR alumnus
Dr Nichollas Scott was a postdoctoral fellow at the lab of Dr. Leonard Foster (2012-2015), and has recently returned to Australia to begin a senior postdoctoral fellow position at the University of Melbourne. Nichollas is a fellow with the National Medical Council Australia CJ Martin and Michael Smith, specializing in the application of proteomic tools to study protein modifications and interactions. Through the support of a CBR Transition Grant, Nichollas began an independent research program on bacterial glycosylation, aiming to investigate its potential as a drug target.
Acinetobacter baumannii is an emerging opportunistic pathogen of significant concern to health care institutions worldwide. Since the 1970s, drug resistance and the ability of this pathogen to survive in harsh environments has led to an increased frequency of high-risk outbreaks in burn and intensive care hospital units. Within these settings, A. baumannii infections cause ventilator-associated pneumonia and wound infections, leading to life-threatening bacteremia/sepsis, especially in immunocompromised populations. Therefore, understanding the mechanisms by which A. baumannii resist the host’s immunological response could go a long way towards preventing further outbreaks in the hospital setting.
A. baumannii – helium ion microscopy. Image from: miphidic.wordpress.com
The survival of A. baumannii within the host’s blood is largely mediated by the generation of different polysaccharides, which coat the bacterial surface and create a dense protective capsule. These capsule structures confer A. baumannii with resistance to complement-mediated killing, allowing replication within the bloodstream and long-term survival on abiotic surfaces. Although in many bacteria, the carbohydrates are exclusively used for capsule generation, within A. baumannii, the capsule monomer can also be conjugated to protein substrates in a process known as protein glycosylation.
Through collaborations between the Foster lab at the CBR and the Feldman lab at the University of Alberta, we were able to characterize the biosynthetic pathways involved in protein glycosylation in A. baumannii bacteria1,2. These pathways are highly conserved and essential for biofilm formation and virulence1,3,4. Our findings demonstrated that a functional glycosylation system is required for virulence in A. baumannii bacteria.
However, the specific role of protein glycosylation in A. baumannii is still unknown, as there is no known mechanism currently linking glycosylations to pathogenesis.
The CBR Transition Grant provided me with a unique opportunity to collect some of the initial data needed to begin an independent research project. In my new position at the University of Melbourne, I am continuing my work on the role of protein glycosylation in bacterial pathogens. I have further expanded these projects to investigate the recently identified glycosylation systems of Burkholderia cenocepacia bacteria and the glycosyltransferase toxin utilized by multiple pathogens. The ability to obtain these initial data and take the first step towards establishing my independent research program would not have been possible without the aid of the CBR transition grant.