Heather Curtsinger - Graduate Student, Immunology, Microbiology, and Virology Ph.D. Program
Conjugative plasmids are responsible for the dissemination of all known antibiotic resistance genes. Genomic surveillance efforts reveal that, although conjugation yields a wide diversity of strain/plasmid combinations, only a small minority of clones and their associated plasmids persist in situ and are clinically relevant. Thus, it is widely believed that the overall fitness of individual strain/plasmid pairs is a key feature of successful pathogens. Currently, plasmid fitness measurements focus on established strain-plasmid combinations. In contrast, the dynamics and factors favoring the initial formation of these combinations are entirely unknown. Understanding these early processes is critical for predicting the emergence of new pathogens, and developing strategies that intervene in plasmid acquisition before they become established in a population. Recently, our lab established a method to quantify the growth defects that occur immediately after conjugation, a phenomenon we refer to as a plasmid’s acquisition cost. Building on this, I found that a plasmid’s acquisition cost depends on the antibiotic used to select for it, indicating an antibiotic-specific effect on plasmid acquisition. Further investigation revealed that newly generated transconjugants exhibit heightened sensitivity to antibiotics compared to their adapted counterparts. This increased sensitivity occurred across different species, plasmid types, and antibiotic classes. Results confirms that the effect of antibiotic selection depends on the time since the plasmid was acquired, and reveals a vulnerable window immediately following plasmid acquisition that can potentially be exploited. Future work will focus on identifying the mechanism by which de novo transconjugants are more sensitive to antibiotics. Overall, this work will aid our general understanding of conjugation dynamics with promising applications in the clinic.
Dec 05, 2024 @ 12:00 p.m.
Medical Center | K307 (3-6408)
Host: Advisor: Allison Lopatkin, PhD