1 The potential impact of coinfection on antimicrobial chemotherapy and drug 1 resistance 2 3 Ruthie Birger* 1 , Roger D. Kouyos* ,2,3 , Ted Cohen 4 , Emily Griffiths 5 , Silvie Huijben 6 , 4 Michael Mina 1,7 , Victoriya Volkova 8 , Bryan Grenfell 1,9 , C. Jessica E. Metcalf* 1,9 5 6 1 Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ USA 7 2 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, 8 University of Zürich, Zürich, Switzerland 9 3 Institute of Medical Virology, University of Zürich, Zürich, Switzerland 10 4 Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, 11 USA 12 5 Department of Entomology, Gardner Hall, Derieux Place, NC State University, Raleigh NC 13 27695 14 6 ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, 15 Barcelona, Spain 16 7 Emory University School of Medicine, Atlanta, GA, USA 17 8 Department of Diagnostic Medicine/Pathobiology, Institute of Computational Comparative 18 Medicine, College of Veterinary Medicine, Kansas State University, USA 19 9 Fogarty International Center, National Institutes of Health, Bethesda, MD, USA 20 21 *These authors contributed equally 22 23 #Corresponding author: 24 Ruthie Birger 25 Dept of Ecology and Evolutionary Biology 26 rbirger@princeton.edu 27 28 Keywords: 29 Drug Resistance, Coinfection, Immune Modulation, Resource Competition, 30 Microbiome, Parasite Interactions 31 32 33 Abstract 34 Across a range of pathogens, resistance to chemotherapy is a growing problem in 35 both public health and animal health. Despite the ubiquity of coinfection, and its 36 potential effects on within-host biology, the role played by coinfecting pathogens on 37 the evolution of resistance and efficacy of antimicrobial chemotherapy is rarely 38 considered. In this review, we provide an overview of the mechanisms of interaction 39 of coinfecting pathogens, ranging from immune modulation, resource modulation, 40 and drug-interactions. We discuss their potential implications for the evolution of 41 resistance, providing evidence in the rare cases where it is available. Overall, our 42 review indicates that the impact of coinfection has the potential to be considerable, 43 suggesting that this should be taken into account when designing antimicrobial drug 44 treatments. 45 46 47 © 2015. This manuscript version is made available under the Elsevier user license http://www.elsevier.com/open-access/userlicense/1.0/