Attention: Restrictions on use of AUA, AUAER, and UCF content in third party applications, including artificial intelligence technologies, such as large language models and generative AI.
You are prohibited from using or uploading content you accessed through this website into external applications, bots, software, or websites, including those using artificial intelligence technologies and infrastructure, including deep learning, machine learning and large language models and generative AI.

Mentorship and Discovery: Developing a Mechanical Alternative to Antibiotic Prophylaxis

By: Maya Ragini Overland, MD, PhD, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine | Posted on: 30 Aug 2023

Worldwide, urinary tract infections (UTIs) impact at least 150 million people each year. Antibiotics are easily accessible and effective when appropriately targeted. However, growing antibiotic resistance patterns related to overuse in humans and in livestock are an increasing threat to public health and food security. Globally, drug-resistant infections are linked to over 700,000 deaths each year. At the patient level, progressively increasing antibiotic resistances with recurrent infections require escalation to broader-spectrum antibiotics with riskier side-effect profiles, including disruption of the systemic microbiome and increased risk of opportunistic infections. Across subspecialities in urology, recurrent UTIs represent one of the most costly and frustrating afflictions that we treat.

Several nonantibiotic UTI prevention strategies have been promising, but none to date has proven to be a broad solution to this pressing problem. A mechanical approach to UTI prophylaxis contingent upon the sequestration and localized killing of pathogenic bacteria, rather than their systemic poisoning, would minimize systemic side effects, eliminate difficult-to-adhere-to daily or weekly treatments, and have the potential for widespread adoption across diverse pediatric and adult patient populations.

Previous engineering studies have demonstrated the ability of complex machined multilayer microscale traps to clear motile bacteria in silico and in vitro.1 The bactericidal and antibiofilm properties of nanopillar surfaces also are well established.2 While training as a resident with Dr Marshall Stoller at the University of California, San Francisco, he and I established a collaboration with Dr Kaushik Chatterjee, a materials scientist with expertise in antimicrobial surfaces at the Indian Institute of Science in Bengaluru, India. As an interinstitutional team, we designed a prototype polymer foam device using a salt-leaching technique to create biocompatible scaffolds with a labyrinth of interconnected pores that function as a novel, easily fabricated bacterial trap (parts A and B of Figure). We also developed a new approach for creating antibacterial textures on flexible surfaces using dry plasma etching.3 In an in vitro proof-of-principle experiment, our porous scaffolds demonstrated a reduction in the number of viable Escherichia coli bacteria in culture solution over a time frame of several hours, with an additive dose-dependent effect from plasma etching of our scaffold surfaces (parts C and D of Figure). Additional preliminary data illustrated the ability of our traps to also clear other motile and nonmotile biofilm-forming bacterial subtypes from culture solution. This year, as a clinical fellow in pediatric urology at the Children’s Hospital of Philadelphia, I am working with Dr Stephen Zderic to test and optimize the ability of these device prototypes to clear uropathogenic bacteria from the bladder in a rodent model of UTI.

image
Figure. A, Scanning electron micrograph demonstrating interconnected pores within a salt-leached polymer scaffold. B, Micrograph of DH5α Escherichia coli accumulated within a scaffold after 24 hours’ incubation in culture solution. C, Micrograph of DH5α E coli skewered on a plasma-etched polymer surface. D, Proof-of-principle experiment demonstrating reduction of viable E coli colony-forming units in culture solution by porous polymer scaffolds and a dose-dependent effect of surface-plasma etching.

Our current interdisciplinary approach has been built through numerous iterations, and will almost certainly require additional redesigns and shifts in perspective along the way. I am incredibly lucky to have found generous surgeon-scientist mentors who encouraged me to seek out-of-the-box solutions to real-world clinical problems and who remain personally invested in solving this particular challenge with me. Over the course of my training, I have learned to always remain open minded to unexpected opportunities, and to never underestimate the value of experienced mentorship and friendships. As I navigate the transition from trainee to academic pediatric urologist in a new terrain of job negotiations and grant applications, the additional mentorship and perspective provided through the AUA USMART (Urology Scientific Mentoring and Research Training) Academy already have proven invaluable, and I look forward to continuing to work closely with my new mentor, Dr Linda Baker.

  1. Giacomo RD, Krödel S, Maresca B, et al. Deployable micro-traps to sequester motile bacteria. Sci Rep. 2017;7(1):1-8.
  2. Jenkins J, Mantell J, Neal C, et al. Antibacterial effects of nanopillar surfaces are mediated by cell impedance, penetration and induction of oxidative stress. Nat Commun. 2020;11(1):1626.
  3. Patil D, Golia V, Overland M, Stoller M, Chatterjee K. Mechanobactericidal nanotopography on nitrile surfaces toward antimicrobial protective gear. ACS Macro Lett. 2023;12(2):227-233.

advertisement

advertisement