Antibiotic degradation by commensal microbes shields pathogens
| Autor: | Eric G. Pamer, James W. Keith, Tobias M. Hohl, Mytrang H. Do, Mergim Gjonbalaj, Simone Becattini |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Antibiotics
Drug Resistance Gut flora medicine.disease_cause Mice Ampicillin Ampicillin/administration & dosage/metabolism/pharmacology chemistry.chemical_classification 0303 health sciences biology Anti-Bacterial Agents/administration & dosage/metabolism/pharmacology Hydrolysis Bacterial Bacterial Infections Anti-Bacterial Agents 3. Good health Intestines Beta-Lactamases/metabolism Infectious Diseases Horizontal gene transfer Clostridium difficile/drug effects/growth & development Listeria monocytogenes/drug effects medicine.drug medicine.drug_class Immunology Microbiology beta-Lactamases 03 medical and health sciences Antibiotic resistance Listeria monocytogenes Drug Resistance Bacterial Escherichia coli medicine Animals Gene 030304 developmental biology Escherichia coli/enzymology/growth & development/metabolism Microbial Viability Clostridioides difficile 030306 microbiology Microbial Viability/drug effects Intestines/microbiology biology.organism_classification Commensalism Enzyme chemistry Microbial Interactions Parasitology Bacteria |
| Zdroj: | Infect Immun Infection and Immunity, Vol. 88, No 4 (2020) pp. e00012-20 |
| ISSN: | 0019-9567 |
| DOI: | 10.1101/870931 |
| Popis: | The complex bacterial populations that constitute the gut microbiota can harbor antibiotic resistance genes (ARGs), including those encoding β-lactamase enzymes (BLA), which degrade commonly prescribed antibiotics such as ampicillin. The prevalence of such genes in commensal bacteria has been increased in recent years by the wide use of antibiotics in human populations and in livestock. While transfer of ARGs between bacterial species has well-established dramatic public health implications, these genes can also function in trans within bacterial consortia, where antibiotic-resistant bacteria can provide antibiotic-sensitive neighbors with leaky protection from drugs, as shown both in vitro and in vivo, in models of lung and subcutaneous coinfection. However, whether the expression of ARGs by harmless commensal bacterial species can destroy antibiotics in the intestinal lumen and shield antibiotic-sensitive pathogens is unknown. To address this question, we colonized germfree or wild-type mice with a model intestinal commensal strain of Escherichia coli that produces either functional or defective BLA. Mice were subsequently infected with Listeria monocytogenes or Clostridioides difficile, followed by treatment with oral ampicillin. The production of functional BLA by commensal E. coli markedly reduced clearance of these pathogens and enhanced systemic dissemination during ampicillin treatment. Pathogen resistance was independent of ARG acquisition via horizontal gene transfer but instead relied on antibiotic degradation in the intestinal lumen by BLA. We conclude that commensal bacteria that have acquired ARGs can mediate shielding of pathogens from the bactericidal effects of antibiotics. |
| Databáze: | OpenAIRE |
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