October 26, 2020

Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage

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dokland2From left: James Kizziah, graduate student and lead author on the study, Dr. Terje Dokland, and Keith Manning, graduate student and co-author on the study; at Rabbit Ears Pass in Colorado. Terje Dokland, Ph.D., professor in the Department of Microbiology, is the latest winner of the School of Medicine’s Featured Discovery. This initiative celebrates important research from School of Medicine faculty members.

Dokland’s study, “Structure of the host cell recognition and penetration machinery of a Staphylococcus aureus bacteriophage,” was recently published in PLOS Pathogens. The first author on the paper was Dokland’s student, James Kizziah. Another of Dokland’s students, Keith Manning, also co-authored the paper.

Bacteriophages or “phages” are viruses that infect and kill bacteria, and are currently being considered for treatments of a variety of bacterial infections. Bacteriophage 80alpha infects Staphylococcus aureus, an important pathogen involved in many diseases. 80alpha is an example of a group of phages that are involved in the horizontal dissemination of mobile genetic elements, such as pathogenicity islands. Dokland says, “In this study, we used high-resolution cryo-electron microscopy to determine the atomic structure of the 80alpha baseplate, a protein complex located at the tip of the bacteriophage tail. The study yields insights into host range determination and the infection and mobilization process.” This information will be important in developing future phage-based therapies.

Dokland and his team’s research on antibiotic-resistant Staphylococcus aureus can lead to more effective treatments and potentially better outcomes for patients, especially from a public health perspective. Their model will provide researchers a basis for developing phage-based strategies to combat and treat antibiotic resistance in S. aureus. In a time when viral infections are so greatly impacting public health, this knowledge is important for research, clinical data, and potential treatments. Read the full publication here..

The School of Medicine communications staff sat down with Dr. Dokland to gain insights about the research of this study, UAB, and the science community.

Q: What compelled you to pursue this research?

I have always been fascinated with molecular machines and how these beautiful and complex structures self-assemble from their protein components. With technical advances in the field of cryo-electron microscopy, it is now possible to determine the atomic resolution structures of these complexes. We have already worked extensively on the “head” part of the bacteriophage and we decided to tackle the “tail” end, specifically the baseplate that is responsible for recognizing the bacterial host, penetrating the host’s cell wall, and injecting the phage genome.

Q: What was your most unexpected finding?

By comparing the 80alpha baseplate structure from those of other bacteriophages, we found that the proteins that make up these complexes are made from a set of modules combined in a “mix-and-match” strategy, and that very different bacteriophages may use many of the same modules if they infect the same host. Our results further strengthen the idea that all tailed bacteriophages are evolutionarily related.

Q: What is your research’s relevance to human disease?

In light of the rise in antibiotic resistance and the paucity of new antibiotics in the development pipeline, bacteriophages are now being considered for therapeutic purposes (known as “phage therapy”). Phages are highly specific to their hosts. A better understanding of how this specificity is defined opens for the possibility to custom design phages for specific purposes.

Q: How has being at UAB and living in Birmingham affected your research?

Birmingham has developed tremendously in the 15 years that I have been at UAB, and it has a lot to offer. We have a good pool of excellent students, such as James Kizziah and Keith Manning, who are co-authors on this study. UAB has made it easy for students and employees to stay engaged with research and do the best work possible.

Q: What made you come to UAB?

I came to UAB after six years in Singapore, and was looking for a larger and more vibrant research environment. UAB was establishing cryo-electron microscopy and was looking for somebody with my exact skill set and research focus, so it was a perfect match.

Read the publication here.