title: Alarmingly High Segregation Frequencies of Quinolone Resistance Alleles within Human and Animal Microbiomes Are Not Explained by Direct Clinical Antibiotic Exposure.
abstract: Antibiotic resistance poses a major threat to human health. It is therefore important to characterize the frequency of resistance within natural bacterial environments. Many studies have focused on characterizing the frequencies with which horizontally acquired resistance genes segregate within natural bacterial populations. Yet, very little is currently understood regarding the frequency of segregation of resistance alleles occurring within the housekeeping targets of antibiotics. We surveyed a large number of metagenomic datasets extracted from a large variety of host-associated and non host-associated environments for such alleles conferring resistance to three groups of broad spectrum antibiotics: streptomycin, rifamycins, and quinolones. We find notable segregation frequencies of resistance alleles occurring within the target genes of each of the three antibiotics, with quinolone resistance alleles being the most frequent and rifamycin resistance alleles being the least frequent. Resistance allele frequencies varied greatly between different phyla and as a function of environment. The frequency of quinolone resistance alleles was especially high within host-associated environments, where it averaged an alarming ∼ 40%. Within host-associated environments, resistance to quinolones was most often conferred by a specific resistance allele. High frequencies of quinolone resistance alleles were also found within hosts that were not directly treated with antibiotics. Therefore, the high segregation frequency of quinolone resistance alleles occurring within the housekeeping targets of antibiotics in host-associated environments does not seem to be the sole result of clinical antibiotic usage.
authors.affiliation: Rachel & Menachem Mendelovitch Evolutionary Processes of Mutation & Natural Selection Research Laboratory, Department of Genetics and Developmental Biology, the Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Wesley
authors.initials: W
authors.lastname: Field
authors.affiliation: Rachel & Menachem Mendelovitch Evolutionary Processes of Mutation & Natural Selection Research Laboratory, Department of Genetics and Developmental Biology, the Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel ruthersh@tx.technion.ac.il.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hershberg
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000145:classification / Q000235:genetics; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D064307:Microbiota / Q000235:genetics*; D015363:Quinolones / Q000494:pharmacology; D012294:Rifamycins / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D015363:Quinolones; D012294:Rifamycins; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D013307:Streptomycin
keywords: allele frequencies; antibiotic resistance; metagenomics; microbiome