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Identifying Gene Regions That Produce Antagonistic Factors Against Multidrug Resistant Pathogens

Crowl, Rachel A
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1625045409764561

Abstract Details

2021, Master of Science (MS), Bowling Green State University, Biological Sciences.
Multidrug resistant (MDR) bacterial infections cause an estimated 700,000 deaths per year worldwide. By the year 2050, it is predicted that MDR infections will account for 10 million deaths and cost 100 trillion dollars per year, becoming the leading cause of death surpassing cancer. Additionally, no major pharmaceutical companies are pursuing research on novel antibiotics, creating a global crisis in which pathogens have evolved resistance to most drugs and very few antibiotics are being discovered. We hypothesize that environmental Pseudomonas isolates that inhibit MDR pathogens produce novel antibiotic compounds with different bacterial targets involving growth and survivability. To test this hypothesis, 384 strains were isolated from the Maumee River in Northwest Ohio and were competed against MDR Pseudomonas aeruginosa and Burkholderia spp. using the Burkholder plate assays. Of 384 environmental isolates, 232 inhibited the growth of the 28 pathogens tested. To identify genes involved in antagonistic activity, we optimized transposon mutagenesis to identify loss of inhibition (LOI) mutants. Following three large-scale mutant hunts, a total of 34 LOI mutants were identified from environmental isolates RC3H12, RC4D1, and RC2C2. Arbitrary PCR and sequencing of the LOI mutants and whole genome sequencing of the wild-type strain were used to identify the biosynthetic gene clusters (BGCs) involved in antibiotic production. Using antiSMASH and JGI/IMG, the potential products of the identified BGCs were determined which include a predicted lipopeptide and sideromycin. The potential antibiotic compounds identified in this research can be further characterized using biochemical testing and bioinformatics which will help to advance the development of novel drugs for use against MDR P. aeruginosa and Burkholderia infections.
Hans Wildschutte, Ph.D. (Advisor)
Tim Davis, Ph.D. (Committee Member)
Vipa Phuntumart, Ph.D. (Committee Member)
90 p.
Biology; Microbiology; Molecular Biology
Cystic Fibrosis; multidrug resistant; antibiotic resistant; environmental Pseudomonas; Pseudomonas aeruginosa; Burkholderia; biosynthetic gene clusters; antibiotic discovery; transposon mutagenesis

Recommended Citations

Citations

  • Crowl, R. A. (2021). Identifying Gene Regions That Produce Antagonistic Factors Against Multidrug Resistant Pathogens [Master's thesis, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1625045409764561

    APA Style (7th edition)

  • Crowl, Rachel. Identifying Gene Regions That Produce Antagonistic Factors Against Multidrug Resistant Pathogens. 2021. Bowling Green State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1625045409764561.

    MLA Style (8th edition)

  • Crowl, Rachel. "Identifying Gene Regions That Produce Antagonistic Factors Against Multidrug Resistant Pathogens." Master's thesis, Bowling Green State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1625045409764561

    Chicago Manual of Style (17th edition)

bgsu1625045409764561
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© 2021, all rights reserved.
This open access ETD is published by Bowling Green State University and OhioLINK.