Table of Contents
International Journal of Antibiotics
Volume 2014, Article ID 185068, 14 pages
Research Article

Effects of Chlorophyll-Derived Efflux Pump Inhibitor Pheophorbide a and Pyropheophorbide a on Growth and Macrolide Antibiotic Resistance of Indicator and Anaerobic Swine Manure Bacteria

1National Center for Agricultural Utilization Research, ARS, USDA, 1815 N. University Street, Peoria, IL 61604, USA
2Leopold Center for Sustainable Agriculture, 209 Curtiss Hall, Iowa State University, Ames, IA 50011, USA

Received 21 October 2013; Revised 12 December 2013; Accepted 19 December 2013; Published 11 February 2014

Academic Editor: Federico Pea

Copyright © 2014 Mareike Kraatz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Natural plant compounds, such as the chlorophyll a catabolites pheophorbide a (php) and pyropheophorbide a (pyp), are potentially active in the gastrointestinal tracts and manure of livestock as antimicrobial resistance-modifying agents through inhibition of bacterial efflux pumps. To investigate whether php, a known efflux pump inhibitor, and pyp influence bacterial resistance, we determined their long-term effects on the MICs of erythromycin for reference strains of clinically relevant indicator bacteria with macrolide or multidrug resistance efflux pumps. Pyp reduced the final MIC endpoint for Staphylococcus (S.) aureus and Escherichia (E.) coli by up to 1536 and 1024 μg erythromycin mL−1 or 1.4- and 1.2-fold, respectively. Estimation of growth parameters of S. aureus revealed that pyp exerted an intrinsic inhibitory effect under anaerobic conditions and was synergistically active, thereby potentiating the effect of erythromycin and partially reversing high-level erythromycin resistance. Anaerobe colony counts of total and erythromycin-resistant bacteria from stored swine manure samples tended to be lower in the presence of pyp. Tylosin, php, and pyp were not detectable by HPLC in the manure or medium. This is the first study showing that pyp affects growth and the level of sensitivity to erythromycin of S. aureus, E. coli, and anaerobic manure bacteria.