Fighting Bacteria on Earth and in Space: Determining Effective Flavonoid-Antibiotic Synergies to Combat Pseudomonas aeruginosa
Is this project an undergraduate, graduate, or faculty project?
Undergraduate
Project Type
individual
Campus
Daytona Beach
Authors' Class Standing
Yegor Bushnev, Junior
Lead Presenter's Name
Yegor Bushnev
Lead Presenter's College
DB College of Arts and Sciences
Faculty Mentor Name
Emel Sen-Kilic
Abstract
Pseudomonas aeruginosa, a Gram-negative pathogen, poses a great risk to immunocompromised populations due to its multidrug resistance. This pathogen is prevalent in hospital environments and has been detected in spaceflight-related settings, including the International Space Station. Astronauts, who often experience immune dysregulation, are particularly vulnerable to infections from P. aeruginosa. Given this, the pathogen has been classified as an urgent threat, underscoring the need for novel countermeasures for astronauts.
One promising alternative to traditional antibiotic interventions for countering multidrug-resistant (MDR) bacteria is flavonoid-antibiotic synergies. Flavonoids are a class of secondary plant phenolics found in various edible vegetables and fruits that have been shown to have antibacterial and anti-oxidative properties via various mechanisms of action. When combined with antibiotics, flavonoids have been found to enhance antibiotic penetration through bacterial biofilms and membranes, boosting antibiotics’ bactericidal effects. In this study, we propose to evaluate the bactericidal effects of five flavonoids on P. aeruginosa and investigate potential flavonoid-antibiotic synergies in both Earth and simulated microgravity conditions.
The central objective is to determine flavonoid-antibiotic synergies that demonstrate significant bactericidal effects on P. aeruginosa in Earth and simulated microgravity conditions. Bacterial growth will be monitored using a multi-mode reader to ensure that bacteria in their exponential growth phase when introduced to flavonoids and flavonoid-antibiotic synergies. In the first phase, flavonoids by themselves will be tested on bacteria to identify minimal inhibitory concentrations (MIC) or sub-inhibitory concentrations. In the second phase, commonly used antibiotics used to treat MDR P. aeruginosa infection will be synergized with the flavonoids identified as having inhibitory activity in phase one and tested for antibacterial activity. Effective flavonoid-antibiotic synergies will then be tested for cytotoxicity on human lung epithelial cells (A549) to ensure that the concentrations of the synergies do not pose significant risks to human cells. In the last phase of this investigation, P. aeruginosa PAO1 will be cultured under standard laboratory conditions and then loaded into RWV bioreactors to be exposed to low shear modeled microgravity (LSMMG) to determine if identified flavonoid-antibiotic synergies remain effective against LSMMG-adapted P. aeruginosa. The results of this study will provide valuable insights into the antibacterial potential of flavonoids and their synergy with antibiotics in combating P. aeruginosa.
This research will also shed light on how P. aeruginosa adapts to microgravity, contributing to the development of new countermeasures for space missions. Additionally, flavonoid-antibiotic synergies could offer innovative solutions to combat MDR pathogens, addressing an emerging public health challenge.
Ultimately, the insights gained could inspire new antimicrobial strategies that improve clinical outcomes on Earth and promote safer, more effective space missions.
Did this research project receive funding support (Spark, SURF, Research Abroad, Student Internal Grants, Collaborative, Climbing, or Ignite Grants) from the Office of Undergraduate Research?
No
Fighting Bacteria on Earth and in Space: Determining Effective Flavonoid-Antibiotic Synergies to Combat Pseudomonas aeruginosa
Pseudomonas aeruginosa, a Gram-negative pathogen, poses a great risk to immunocompromised populations due to its multidrug resistance. This pathogen is prevalent in hospital environments and has been detected in spaceflight-related settings, including the International Space Station. Astronauts, who often experience immune dysregulation, are particularly vulnerable to infections from P. aeruginosa. Given this, the pathogen has been classified as an urgent threat, underscoring the need for novel countermeasures for astronauts.
One promising alternative to traditional antibiotic interventions for countering multidrug-resistant (MDR) bacteria is flavonoid-antibiotic synergies. Flavonoids are a class of secondary plant phenolics found in various edible vegetables and fruits that have been shown to have antibacterial and anti-oxidative properties via various mechanisms of action. When combined with antibiotics, flavonoids have been found to enhance antibiotic penetration through bacterial biofilms and membranes, boosting antibiotics’ bactericidal effects. In this study, we propose to evaluate the bactericidal effects of five flavonoids on P. aeruginosa and investigate potential flavonoid-antibiotic synergies in both Earth and simulated microgravity conditions.
The central objective is to determine flavonoid-antibiotic synergies that demonstrate significant bactericidal effects on P. aeruginosa in Earth and simulated microgravity conditions. Bacterial growth will be monitored using a multi-mode reader to ensure that bacteria in their exponential growth phase when introduced to flavonoids and flavonoid-antibiotic synergies. In the first phase, flavonoids by themselves will be tested on bacteria to identify minimal inhibitory concentrations (MIC) or sub-inhibitory concentrations. In the second phase, commonly used antibiotics used to treat MDR P. aeruginosa infection will be synergized with the flavonoids identified as having inhibitory activity in phase one and tested for antibacterial activity. Effective flavonoid-antibiotic synergies will then be tested for cytotoxicity on human lung epithelial cells (A549) to ensure that the concentrations of the synergies do not pose significant risks to human cells. In the last phase of this investigation, P. aeruginosa PAO1 will be cultured under standard laboratory conditions and then loaded into RWV bioreactors to be exposed to low shear modeled microgravity (LSMMG) to determine if identified flavonoid-antibiotic synergies remain effective against LSMMG-adapted P. aeruginosa. The results of this study will provide valuable insights into the antibacterial potential of flavonoids and their synergy with antibiotics in combating P. aeruginosa.
This research will also shed light on how P. aeruginosa adapts to microgravity, contributing to the development of new countermeasures for space missions. Additionally, flavonoid-antibiotic synergies could offer innovative solutions to combat MDR pathogens, addressing an emerging public health challenge.
Ultimately, the insights gained could inspire new antimicrobial strategies that improve clinical outcomes on Earth and promote safer, more effective space missions.