title: Collective Resistance in Microbial Communities by Intracellular Antibiotic Deactivation.
abstract: The structure and composition of bacterial communities can compromise antibiotic efficacy. For example, the secretion of β-lactamase by individual bacteria provides passive resistance for all residents within a polymicrobial environment. Here, we uncover that collective resistance can also develop via intracellular antibiotic deactivation. Real-time luminescence measurements and single-cell analysis demonstrate that the opportunistic human pathogen Streptococcus pneumoniae grows in medium supplemented with chloramphenicol (Cm) when resistant bacteria expressing Cm acetyltransferase (CAT) are present. We show that CAT processes Cm intracellularly but not extracellularly. In a mouse pneumonia model, more susceptible pneumococci survive Cm treatment when coinfected with a CAT-expressing strain. Mathematical modeling predicts that stable coexistence is only possible when antibiotic resistance comes at a fitness cost. Strikingly, CAT-expressing pneumococci in mouse lungs were outcompeted by susceptible cells even during Cm treatment. Our results highlight the importance of the microbial context during infectious disease as a potential complicating factor to antibiotic therapy.
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen, The Netherlands.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Sorg
authors.affiliation: Department of Pediatrics University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Leo
authors.initials: L
authors.lastname: Lin
authors.affiliation: Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.
authors.forename: G Sander
authors.initials: GS
authors.lastname: van Doorn
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen, The Netherlands.
authors.forename: Moritz
authors.initials: M
authors.lastname: Sorg
authors.affiliation: Department of Pediatrics University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Joshua
authors.initials: J
authors.lastname: Olson
authors.affiliation: Department of Pediatrics University of California, San Diego, La Jolla, California, United States of America.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen, The Netherlands.|Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Veening
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents