Metabolic Potentation of Antibiotic Lethality from Carbon Source Preference in P. aeruginosa and S. aureus
Abstract
Antimicrobial resistance (AMR) is a growing public health concern with a dire need for new solutions. This problem has only been exacerbated in recent years due to the misuse of antibiotics and globalization. As new antibiotic drugs are costly and time-intensive, it is imperative to understand and study creative new ways to combat AMR. In both natural ecosystems and clinical infections, microorganisms seldom exist in isolation. Rather, they flourish within polymicrobial communities, presenting unique challenges for therapeutic interventions owing to elaborate inter-species interactions. Two such pathogens are Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA); bacteria commonly found in patients with cystic fibrosis, and severe burn wounds. These two pathogens have an intricate relationship involving virulence factors, competitive inhibition, and metabolic hijacking that further drive AMR, making PA + SA co-infections notoriously difficult to treat. Notably, recent work has uncovered a connection between bacterial metabolic state and antibiotic efficacy. Given that antibiotics target energy-consuming processes, the manipulation of bacterial metabolism may serve as a potential avenue to enhance the effectiveness of antibiotic treatment. Our hypothesis is that growth medium supplemented with various carbon sources may increase the metabolic rate of S. aureus enough to shield it from the effects of P. aeruginosa’s virulence factors, increasing the sensitivity of S. aureus to aminoglycoside antibiotics. To test for this, adenosine triphosphate (ATP) was quantified for PA and SA with various carbon sources to serve as an indicator of metabolic rate. Additionally, minimum inhibitory concentrations (MIC) were quantified for the aminoglycoside antibiotic, kanamycin, and were found to be altered in response to carbon source supplementation. Next, we found a reduction in MIC for SA when co-cultured with PA, suggesting metabolic state can be altered due to the metabolite source. Taken together, these results show that antibiotic efficacy can be successfully modulated via metabolic perturbations and re-shape the community composition of this infection. This research has implications for future antibiotic adjuvants and personalized medicine, effectively extending the shelf-life of existing antibiotics while new antibiotics are being discovered.
Faculty Sponsors
Dr. Robert Smith
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Metabolic Potentation of Antibiotic Lethality from Carbon Source Preference in P. aeruginosa and S. aureus
Alvin Sherman Library
Antimicrobial resistance (AMR) is a growing public health concern with a dire need for new solutions. This problem has only been exacerbated in recent years due to the misuse of antibiotics and globalization. As new antibiotic drugs are costly and time-intensive, it is imperative to understand and study creative new ways to combat AMR. In both natural ecosystems and clinical infections, microorganisms seldom exist in isolation. Rather, they flourish within polymicrobial communities, presenting unique challenges for therapeutic interventions owing to elaborate inter-species interactions. Two such pathogens are Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA); bacteria commonly found in patients with cystic fibrosis, and severe burn wounds. These two pathogens have an intricate relationship involving virulence factors, competitive inhibition, and metabolic hijacking that further drive AMR, making PA + SA co-infections notoriously difficult to treat. Notably, recent work has uncovered a connection between bacterial metabolic state and antibiotic efficacy. Given that antibiotics target energy-consuming processes, the manipulation of bacterial metabolism may serve as a potential avenue to enhance the effectiveness of antibiotic treatment. Our hypothesis is that growth medium supplemented with various carbon sources may increase the metabolic rate of S. aureus enough to shield it from the effects of P. aeruginosa’s virulence factors, increasing the sensitivity of S. aureus to aminoglycoside antibiotics. To test for this, adenosine triphosphate (ATP) was quantified for PA and SA with various carbon sources to serve as an indicator of metabolic rate. Additionally, minimum inhibitory concentrations (MIC) were quantified for the aminoglycoside antibiotic, kanamycin, and were found to be altered in response to carbon source supplementation. Next, we found a reduction in MIC for SA when co-cultured with PA, suggesting metabolic state can be altered due to the metabolite source. Taken together, these results show that antibiotic efficacy can be successfully modulated via metabolic perturbations and re-shape the community composition of this infection. This research has implications for future antibiotic adjuvants and personalized medicine, effectively extending the shelf-life of existing antibiotics while new antibiotics are being discovered.
