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Effectiveness of Novel Compounds at Inhibiting and Killing Acinetobacter baumannii Biofilms

Latimer, Keye S.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337886639

Abstract Details

2012, MS, University of Cincinnati, Medicine: Molecular Genetics, Biochemistry, and Microbiology.
In the past two decades Acinetobacter baumannii (Ab) has grown from relative obscurity to one of the most important global nosocomial infections. Ab is classified as a low grade pathogen, infecting only the immunocompromised. Overtime, Ab has evolved the capability to incorporate extraneous DNA into its own genome which has led to a dramatic increase in resistance to conventional antibiotics. To compound the problem, Ab can form biofilms which provide an even greater level of resistance against antibiotics and environmental pressures including biocides and desiccation. Adherent properties of Ab biofilms enable the organism to grow on a variety of surfaces and medical devices composed of glass, plastic or steel and instruments including stethoscopes and ventilator tubing. A previous study was conducted using High-Throughput Screening (HTS) to identify novel compounds that are capable of killing and/or inhibiting biofilm formation of Pseudomonas aeruginosa (Pa) or Staphylococcus epidermidis (Se) and Acinetobacter baumannii (Ab) biofilms. The novel compounds were divided into 5 groups based on the HTS results against one or more of the microorganisms. The first group of compounds (designated 3, 7, 8 and 11) were effective against Pa, Se and Ab biofilms. Group 2 compounds (1, 2, 9, 10, 12, and 13) were effective against only Pa and Ab biofilms. Group 3 compounds (14, 15 and 16) were effective only against Pa biofilms. Group 4 compounds (Se1 to Se16) were effective only against Se biofilm. Finally, group 5 compounds (17 to 34) were effective only against Ab biofilm. The biofilms were challenged in two phases. The first phase determined the compounds' ability to inhibit the initial formation of a biofilm. The second phase determined the compounds' ability to kill a mature biofilm. Confocal Laser Scanning Microscopy (CLSM) was used to study the effects of the compounds on initial biofilm formation and killing of mature biofilm. Of the compounds examined for inhibiting initial Ab biofilm formation, two compounds (17 and 24) exhibited slight inhibition and five compounds (1-3, 7, 8, 12, 13 and 18) were positive for biofilm inhibition. Of the compounds examined for killing Ab biofilm, six (18, 24, 26, 28, 31 and 34) were positive. A minimal inhibitory concentration (MIC) assay was performed for only group 1 (compounds 3, 7, 8 and 11) on Ab. Compounds 3, 8 and 11 showed inhibitory effects below 10 ¿¿¿¿M while compound 7 did not demonstrate inhibitory effects below 16 ¿¿¿¿M. Lastly, the group of compounds that were effective in inhibition and/or killing was screened for cytotoxicity using airway A549 and differentiated THP-1 human monocyte/macrophage cell lines. Compounds 18, 24, 26, 28, 31 and 34 were negative for cytotoxicity (<30%) in the A549 human cell line 300 ¿¿¿¿M and below. THP-1 Cytotoxicity (>40%) was observed in compounds 18, 24, 26, 28, 31 and 34, respectively. We conclude that while this group of compounds are effective at killing Ab biofilm, these compounds may not be suitable for clinical applications. However, these compounds could be used industrially in fuel tanks and heavy equipment.
Daniel Hassett, PhD (Committee Chair)
Thomas Lamkin, PhD (Committee Member)
Edmund Choi, PhD (Committee Member)
70 p.
Microbiology
Biofilm; Acinetobacter; Cytotoxicity;

Recommended Citations

Citations

  • Latimer, K. S. (2012). Effectiveness of Novel Compounds at Inhibiting and Killing Acinetobacter baumannii Biofilms [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337886639

    APA Style (7th edition)

  • Latimer, Keye. Effectiveness of Novel Compounds at Inhibiting and Killing Acinetobacter baumannii Biofilms. 2012. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337886639.

    MLA Style (8th edition)

  • Latimer, Keye. "Effectiveness of Novel Compounds at Inhibiting and Killing Acinetobacter baumannii Biofilms." Master's thesis, University of Cincinnati, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337886639

    Chicago Manual of Style (17th edition)

ucin1337886639
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© 2012, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.