The RCS Phosphorelay's Role in the Development of Antibiotic Resistance

ABSTRACT

In the world today, levels of antibiotic resistance are continuing to arise exponentially (1). If a mechanism is found that explains what causes a strain of E. coli to be resistant to specific drugs, for example to β-lactam antibiotics, it is possible that this information could be used by researchers to develop new drugs that target specific pathways of interest (2). This information may help retard the increased movement of resistance and extend thousands of lives. When analyzing stress responses of E. coli, it is likely the level of activity of the Rcs phosphorelay is a major contributor to the increased resistance levels to mecillinam (2). While it is known that the Rcs phosphorelay increases survival of E. coli in the presence of antibiotics like mecillinam, it is not well documented which parts of the pathway provide the resistance and to what magnitude. This information could be essential for the creation of new antibiotics. E. coli mutants were isolated on different concentrations of mecillinam (0.3ug/ml, 3ug/ml and 30ug/ml) and analyzed. The resistance of these mutants to mecillinam on plates and in liquid did not correlate to the concentration of mecillinam on which they were isolated. To determine if specific genes in the Rcs pathway were important for resistance, each gene was individually deleted in a resistant mutant and resistance was measured to see if it was decreased. It was found that mutants resistant to mecillinam were dependent Rcs F and RcsB, but not RcsA. In addition to analyzing mutants that were isolated on mecillinam, mutants isolated for resistance to cefsulodin were tested for cross resistance to mecillinam. The importance of the Rcs pathway was then analyzed. For those mutants exhibiting cross resistance, it was found that cross resistant mutants were dependent on all parts of the Rcs phosphorelay, contradictory to the results generated by the mecillinam mutants.

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Work Title The RCS Phosphorelay's Role in the Development of Antibiotic Resistance
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Penn State
Creators
  1. Jordan Antetomaso
Keyword
  1. Biochemistry and Molecular Biology
  2. antibiotic resistance
  3. RCS Phosphorelay
  4. E.coli
License Attribution-NonCommercial-NoDerivs 3.0 United States
Work Type Thesis
Acknowledgments
  1. Thomas Mallouk - thesis reader
  2. Sarah Ades - research mentor
Publisher
  1. Eberly College of Science
  2. Department of Biochemistry and Molecular Biology
Publication Date Spring 2015
Subject
  1. Biochemistry and Molecular Biology
Language
  1. English
Deposited June 22, 2016

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