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Induced Resistance to the Designer Proline-rich Antimicrobial Peptide A3-APO does not Involve Changes in the Intracellular Target DnaK

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Abstract

The designer proline-rich antimicrobial peptide A3-APO and its Chex1-Arg20 single chain in vivo metabolite were studied for their ability to induce bacterial resistance upon repeated incubation of Escherichia coli and Klebsiella pneumoniae strains in sublethal concentrations. While no resistant E. coli phenotype emerged to either peptides, after 10 passages the K. pneumoniae strain became resistant to the monomer but not the dimer. The major microbiological difference between A3-APO and Chex1-Arg20 is the improved membrane-disintegrating ability of the dimeric prodrug. Thus, in agreement with earlier studies, the induced resistance likely resides in some membrane component rather than the intracellular target protein DnaK. In support, no genetic alteration in the DnaK multihelical lid region could be observed in any of the sensitive or resistant bacterial strains.

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Abbreviations

AMP:

Antimicrobial peptide

ATP:

Adenosine triphosphate

cfu:

Colony forming units

MIC:

Minimal inhibitory concentration

PCR:

Polymerase chain reaction

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Authors and Affiliations

  1. Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA, USA

    Marco Cassone

  2. Sbarro Institute for Cancer Research and Molecular Medicine, Physician Student Training Program, Temple University, Philadelphia, PA, USA

    Nikea Frith

  3. Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA

    Paraskevi Vogiatzi

  4. Howard Florey Institute, University of Melbourne, Melbourne, Victoria, Australia

    John D. Wade

  5. Department of Biology, Temple University, Philadelphia, PA, USA

    Laszlo Otvos Jr.

  6. OLPE, LLC, 801 Mockingbird Lane, Audubon, PA, 19403, USA

    Laszlo Otvos Jr.

Authors
  1. Marco Cassone
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  2. Nikea Frith
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  3. Paraskevi Vogiatzi
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  4. John D. Wade
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  5. Laszlo Otvos Jr.
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Correspondence to Laszlo Otvos Jr..

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Cassone, M., Frith, N., Vogiatzi, P. et al. Induced Resistance to the Designer Proline-rich Antimicrobial Peptide A3-APO does not Involve Changes in the Intracellular Target DnaK. Int J Pept Res Ther 15, 121–128 (2009). https://doi.org/10.1007/s10989-009-9176-1

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  • DOI: https://doi.org/10.1007/s10989-009-9176-1

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