We study the behaviors of bacterial pathogens during polymicrobial infections, specifically how they interact with the host and other co-inhabiting microbes to form unique ecological niches that evade immune clearance and resist stressors such as antibiotics.
Research
Bacteria, similar to higher animals, exhibit remarkable versatility by altering their behaviors in different environments. While microbiologists often study bacteria under standard lab conditions, our knowledge of bacterial functions in their natural habitats (e.g. humans, soils) is limited. Our lab is dedicated to using various state-of-the-art approaches to unravel how bacterial pathogens (such as Pseudomonas aeruginosa) behave during polymicrobial infection in the human host.
By directly examining bacterial gene expression in clinical samples, we have begun to understand P. aeruginosa physiology in humans. We discovered a key small regulatory RNA called SicX, which plays a critical role in orchestrating the transition between bacterial chronic persistence and acute exacerbation. Leveraging information on bacterial gene expression within human hosts, we can better understand how P. aeruginosa modulates its behaviors during infection and identify clinically relevant targets for therapeutic intervention. Building upon this discovery, our lab focuses on addressing several major questions:
How does SicX sRNA govern bacterial chronic or acute infection?
We've established the roles of SicX in vitro in response to oxygen deprivation, but how it governs bacterial lifestyle choice during infection requires further study. Filling this gap is critical for designing new therapies against this important pathogenic trait.
What are the roles of other bacterial sRNAs and small proteins in human infections?
The discovery of SicX sRNA is just the tip of the iceberg, and our knowledge of bacterial small regulatory elements remains limited to a few examples. Our goal is to uncover and characterize diverse sRNAs and small proteins that govern bacterial infections.
How do inter- and intra-species communication influence infection progression and outcomes?
Bacterial populations within the host often exhibit physiological heterogeneity and genetic diversity. Moreover, various microbial species often coexist and show intricate interactions with host cells. We aim to explore how novel mechanisms of cell-cell communication can shape the dynamics of bacterial infections.
Overall, our lab is dedicated to elucidating the multifaceted roles of small regulatory elements in bacterial behaviors and their implications for human health.
People
Alumni
2023-2024: Chao Gao, Research Assistant
2023-2024: Shuhan Shi, Admin Assistant
Publications
, Fleming, D., Moustafa, D. A., Dolan, S. K., Szymanik, K. H., Redman, W. K., Ramos, A., Diggle, F. L., Sullivan, C. S., Goldberg, J. B., Rumbaugh, K. P., and Whiteley, M. (2023). A Pseudomonas aeruginosa small RNA regulates chronic and acute infection. Nature. Link Research briefing
Ibberson, C. B., Barraza, J. P., Holmes, A. L., , and Whiteley, M. (2022). Precise spatial structure impacts antimicrobial susceptibility of S. aureus in polymicrobial wound infections. Proceedings of the National Academy of Sciences, 119(51), e2212340119. Link
Balagam, R., (co-first), Sah, G. P., Zhang, Z., Subedi, K., Wall, D., and Igoshin, O. A. (2021). Emergent myxobacterial behaviors arise from reversal suppression induced by kin contacts. mSystems, 6(6), e00720-21. Link
Sah, G. P., , and Wall, D. (2020). MYXO‐CTERM sorting tag directs proteins to the cell surface via the type II secretion system. Molecular Microbiology, 113(5), 1038-1051. Link
[Review article] , and Wall, D. (2020). The Fluidity of the Bacterial Outer Membrane Is Species Specific: Bacterial Lifestyles and the Emergence of a Fluid Outer Membrane. BioEssays, 1900246. Link
and Wall D. (2019). Direct visualization of a molecular handshake that governs kin recognition and tissue formation in myxobacteria. Nature Communications. 10(1), 1-10. Link Behind the paper
, Wei X., Awal R., Müller R., and Wall D. (2019). A highly polymorphic receptor governs many distinct self-recognition types within the Myxococcales order. mBio. e02751-18. Link
[Review article] Troselj V., (co-first) and Wall D. (2017). Cell-cell recognition and social networking in bacteria. Environmental Microbiology. doi:10.1111/1462-2920.14005. Link
and Wall D. (2017). Self-identify reprogrammed by a single residue switch in a cell surface receptor of a social bacterium. Proceedings of the National Academy of Sciences. Link
Vassallo C., , Conklin A., Finkelstein H., Hayes C., and Wall D. (2017). Infectious polymorphic toxins delivered by outer membrane exchange discriminate kin in myxobacteria. eLife. 6:e29397. Link
Vassallo C., Pathak D.T., , Zuckerman D.M., Hoiczyk E., and Wall D. (2015). Cell rejuvenation and social behaviors promoted by LPS exchange in myxobacteria. Proceedings of the National Academy of Sciences. 112(22):E2939-46. Link
[Review article] , Dey A., Vassallo C. and Wall D. (2015). How myxobacteria cooperate. Journal of Molecular Biology. 427:3709-3721. Link
Join Us
We aim to foster an inclusive and collaborative environment where individuals from diverse backgrounds feel comfortable expressing their opinions and are encouraged to thrive as independent scientists. We mentor individuals to perceive the 'big picture' of their research project, while developing robust expertise in conducting mechanistic work. If you are interested in joining our lab, see the opportunities below.
Intrigued by our research focus and our approach to tackle scientific questions? We welcome those with a PhD (or those on track to obtain one) in various disciplines to join us. Please email Pengbo your CV, a brief description of your research interests, and the contact information of at least two referees.
We are affiliated with the School of Life Sciences at Westlake University. Please visit the website to apply for the PhD program. Already admitted and interested in a lab rotation? Reach out to Pengbo via email to arrange a meeting.
Fresh out of college and interested in gaining research experience? Please email Pengbo your CV and briefly explain why you are interested in getting involved in our research.
News
A few personnel changes over the past few months: Farewell to our all-star research assistant Hantao and admin assistant Shuhan, who helped tremendously setting up our lab and getting things off the ground. We will miss you both! On a brighter note, we are thrilled to welcome our new admin assistant Yang Xiao, our postdoc Zijing, and our visiting students Yongmei and Danni. Exciting summer research awaits!
New year, new group photo! Welcome to our newest lab member, Haoru.
The lab starts. A warm welcome to Xiaolin, Hantao, Chao and Feihang. Let the adventures begin!
Best approach to contact Pengbo is via email: caopengbo@westlake.edu.cn