Congratulations to Rico Carale for being selected to share his research at St Jude Children's Research Hospital National Symposium for Undergraduate Research.
This Symposium featured 52 undergraduate researchers from institutions across the US and provided students with an opportunity to share their research with faculty, staff, and trainees across St. Jude. The participating students were introduced to the incredibly rich research environment at St. Jude Children’s Research Hospital. The Symposium helped bolster conversations, interactions and expanded the students’ network to stimulate a creative exchange of ideas and be personally rewarding to each participant.
Rico presented in the Genetics, Cell Biology and Signaling session.
How to evade a predator: Complex extracellular structures defend against predatory bacteria
Ricardo O. Carale1, Hannah E. Ledvina1, Ryan Sayegh2, Ashley L. Azadeh2, Aaron T. Whiteley1.
1Department of Biochemistry, University of Colorado, Boulder, CO, USA
2Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, CO, USA
Abstract
Antibiotic-resistant infections are an imminent threat to global public health. In 2019, antibiotic-resistant infections killed approximately 1.2 million people worldwide, and projections estimate this annual death toll could rise to 10 million people by 2050. Due to this rapidly expanding threat, scientists are racing to develop novel therapeutics against pathogenic bacteria. One proposed approach is using predatory bacteria as a “living antibiotic.” Predatory bacteria are potent pathogens of other bacteria capable of eradicating a prey population within 24 hours. However, for living antibiotics to be considered feasible treatments, we must better understand the interactions between predatory bacteria and their prey.
One of the predatory bacteria being studied as a potential living antibiotic is Bdellovibrio bacteriovorus, a Gram-negative predatory bacterium that preys on other Gram-negative bacteria, such as the pathogens Escherichia coli and Pseudomonas aeruginosa. B. bacteriovorus breaches the outer membrane of prey cells, drains the prey of nutrients, and proliferates within this intracellular niche. Interestingly, genetically-encoded defense mechanisms against B. bacteriovorus predation have not yet been reported; however, we hypothesized that this is because past research has focused on lab strains as prey, which notoriously lack genes implicated in defense from diverse threats. To test this hypothesis, I screened 72 wild strains of E. coli against B. bacteriovorus with the goal of identifying and characterizing an anti-B. bacteriovorus system. Excitingly, I identified 30 E. coli that exhibited over ten-thousand-fold resistance to B. bacteriovorus. We then used transposon mutagenesis to identify the genetic determinants of resistance. Surprisingly, we discovered that many of the resistant E. coli relied on an elaborate extracellular structure to defend themselves against B. bacteriovorus. These structures have been implicated in biofilm formation; however, their role in bacterial defense has yet to be elucidated. Our findings establish that extracellular structures serve as the first characterized genetically-encoded defense mechanism against B. bacteriovorus. This study indicates that researchers must consider the existing natural defenses against predatory bacteria when exploring B. bacteriovorus as a living antibiotic.