Author: Christy Groves
Huge congratulations to Dr. Andrew Pawlowski of the Wright lab for successfully defending his thesis this month. We had a chance to sit down with (the very busy!) Andrew, to ask him a few questions regarding his love for cooking up experiments, his area of research at the IIDR, and his goals for the future.
Make sure not to miss Dr. Pawlowski’s talk with Dr. Martha Fulford entitled “One Health – People, Animals, and the Environment” at this month’s ID/IIDR Combined Rounds. Rounds take place from 8:00am – 9:00am on Wednesday, December 6th in MUMC, HSC 4E20.
Tell me about yourself.
I was born in Toronto. I really enjoy cooking, and I approach it in the same way as I approach research; I know what I am trying to make, but instead of following established recipes I use my knowledge base to experiment and concoct new dishes. I also love to read novels such as those by David Foster Wallace, J.G. Ballard, and William S. Burroughs.
Where did you go to school prior to your PhD?
I completed my undergraduate degree in biochemistry with a co-op component at the University of Guelph. I worked in the laboratory of Dr Joe Lam, where I studied enzymes involved in lipopolysaccharide biosynthesis.
What was your area of research at the IIDR?
I completed my PhD with Dr Gerry Wright, where I studied the natural evolution of antibiotic resistance in environmental bacteria, focusing particularly on the genomic evolution of resistome genotypes. My research was important because resistance genes in pathogenic bacteria likely originated in environmental bacteria.
At the beginning of graduate school, I was involved in surveying antibiotic resistance in a collection of bacteria from Lechuguilla Cave. This cave is special because it was isolated from the surface for over four million years, and wastewater contaminated with antibiotics from medical or agricultural use has not influenced the development of resistance in these bacteria. Long story short, every bacteria were multi-drug resistant. One of these bacteria, a strain of Paenibacillus, was particularly interesting because it was resistant to most antibiotic drugs, and so I sequenced its genome. I found 18 different resistance elements including 5 mechanisms not previously discovered!
I then studied the relationship between bacterial diversity and resistance diversity in the Paenibacillaceae family of bacteria and found evidence of horizontal transfer of resistance genes. Mobile genetic elements transfer resistance genes into pathogenic bacteria. In contrast, only some resistance genes in Paenibacillaceae were possibly on mobile genetic elements. Therefore, we think that resistance genes may be stochastically captured by mobile genetic elements in bacteria because of natural genome evolution, which then become primed for their dissemination in pathogens.
I also developed a general strategy for understanding and predicting the functional evolution of resistance enzymes. Antibiotic drug development requires methods for assessing the potential for resistance to evolve. This strategy can help drug discoverers focus on new antibiotics where resistance is likely to evolve at a slower pace.
What are your plans for the future?
In January, I will begin a postdoctoral position with Dr. George Church at Harvard Medical School, where I will develop in situ genomics-based technologies for interrogating microbes in their natural environments. The lives of bacteria are relatively unknown because we lack the tools for investigating their interactions with neighbours and environments. My Ph.D. research into antibiotic resistance led to questions such as how does natural antibiotic production by microbes impact bacterial communities and does this select for resistance development, as we presume. The technologies I will develop in Dr. George Church’s lab will provide the means to ask such questions, and will ultimately be paired with synthetic biology approaches for generating biofuels.
- Pawlowski AC, Stogios PJ, Koteva K, Skarina T, Evdokimova E, Savchenko A, and Wright GD. (2017) The evolution of substrate discrimination in macrolide antibiotic resistance enzymes. Nature Communications, Accepted. Stay tuned, will be out shortly!
- Pawlowski AC, Westman EL, Koteva K, Waglechner N, and Wright GD. (2017) The complex resistomes of Paenibacillaceae reflect diverse antibiotic chemical ecologies. ISME Journal, Accepted.Stay tuned, will be out shortly!
- Cox G, Sieron A, King AM, De Pascale G, Pawlowski AC, Koteva K and Wright GD. (2017) A common platform for antibiotic dereplication and adjuvant discovery. Cell Chemical Biology 24:98-109. PMID: 28017602 http://www.cell.com/cell-chemical-biology/abstract/S2451-9456(16)30434-2
- Pawlowski AC, Wang W, Koteva K, Barton HA, McArthur AG and Wright GD. (2016) A diverse intrinsic antibiotic resistome from a cave bacterium. Nature Communications 7:13803. PMID: 27929110 https://www.nature.com/articles/ncomms13803
- Jia B et al. (2017) CARD 2017: expansion and model-centric curation of the Comprehensive Antibiotic Resistance Database. Nucleic Acids Research, 45(D1):D566-D573. PMID 27789705https://academic.oup.com/nar/article/45/D1/D566/2333912
- Pawlowski AC, Johnson JW, and Wright GD. (2016) Evolving medicinal chemistry strategies in antibiotic discovery, Current Opinion Biotechnology 42:108-117. PMID: 27116217 http://www.sciencedirect.com/science/article/pii/S0958166916301148?via%3Dihub
- McArthur AG et al. (2013) The Comprehensive Antibiotic Resistance Database. Antimicrobial Agents and Chemotherapy 57(7):3348-57. PMID: 23650175 http://aac.asm.org/content/57/7/3348.full
- Bhullar K, Waglechner N, Pawlowski A, Koteva K, Banks ED, Johnston MD, Barton HA and Wright GD. (2012) Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS ONE 7(4): e34953. PMID: 22509370 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034953