Targeting Respiratory Pathways to Combat Persistence: Investigating the Role of Respiratory Complexes in Klebsiella Aerogenes Persister Cell Formation

Access to IIT electronic theses and dissertations is restricted to IIT community members with a valid iit.edu email address. Please log in using your iit.edu email address and password. Requests for external users are handled through inter-library loan and can be emailed to iitmyillms@iit.edu.

Description

Klebsiella aerogenes is a multidrug-resistant nosocomial pathogen that poses significant challenges due to its ability to form persister cells that evade antibiotic treatment and contribute to chronic infections. This study explored the relationship between respiratory complexes and persister... Show moreKlebsiella aerogenes is a multidrug-resistant nosocomial pathogen that poses significant challenges due to its ability to form persister cells that evade antibiotic treatment and contribute to chronic infections. This study explored the relationship between respiratory complexes and persister cell formation, focusing on NDH-2, NQR, and cytochrome oxidases. The research used a combination of wild-type and mutant strains, along with respiratory inhibitors and antibiotics, to identify key metabolic pathways influencing persister survival.The results revealed that NDH-2 plays a pivotal role in persister cell formation, with NDH-2 mutants demonstrating a significant reduction in persister populations over time. Comparative analysis of respiratory mutants highlighted differential reliance on oxidative phosphorylation, with NDH-2 being essential for maintaining energy metabolism during stress. In contrast, mutants lacking NQR or nuo complexes exhibited slower colony count declines, suggesting a shift to low-energy states that mimic persister characteristics.
These findings emphasize the critical role of the respiratory chain, particularly NDH-2, in bacterial persistence and highlight its potential as a therapeutic target. By disrupting energy metabolism, it may be possible to eradicate persister cells and reduce the recurrence of infections caused by K. aerogenes, providing a promising avenue for combating multidrug-resistant pathogens. Show less

Details
Department

BIOL / Biology

Title

Targeting Respiratory Pathways to Combat Persistence: Investigating the Role of Respiratory Complexes in Klebsiella Aerogenes Persister Cell Formation

Institution

Illinois Institute of Technology

Creator(s)

Barnes, Alyssa Britney

Advisor(s)

Tuz, Karina

Date

2024

Description

Klebsiella aerogenes is a multidrug-resistant nosocomial pathogen that poses significant challenges due to its ability to form persister cells that evade antibiotic treatment and contribute to... Show moreKlebsiella aerogenes is a multidrug-resistant nosocomial pathogen that poses significant challenges due to its ability to form persister cells that evade antibiotic treatment and contribute to chronic infections. This study explored the relationship between respiratory complexes and persister cell formation, focusing on NDH-2, NQR, and cytochrome oxidases. The research used a combination of wild-type and mutant strains, along with respiratory inhibitors and antibiotics, to identify key metabolic pathways influencing persister survival.The results revealed that NDH-2 plays a pivotal role in persister cell formation, with NDH-2 mutants demonstrating a significant reduction in persister populations over time. Comparative analysis of respiratory mutants highlighted differential reliance on oxidative phosphorylation, with NDH-2 being essential for maintaining energy metabolism during stress. In contrast, mutants lacking NQR or nuo complexes exhibited slower colony count declines, suggesting a shift to low-energy states that mimic persister characteristics. These findings emphasize the critical role of the respiratory chain, particularly NDH-2, in bacterial persistence and highlight its potential as a therapeutic target. By disrupting energy metabolism, it may be possible to eradicate persister cells and reduce the recurrence of infections caused by K. aerogenes, providing a promising avenue for combating multidrug-resistant pathogens. Show less

Type

Thesis

File type

application/pdf

Subject

Biology
Klebsiella aerogenes
metabolically active
period of dormancy
persisters
respiratory inhibitors
respiratory mutants

Access

Restricted Access

Rights

In Copyright
http://rightsstatements.org/page/InC/1.0/

<p></p><p></p>