Antibiotic failure mediated by a resistant subpopulation in Enterobacter cloacae
Autor: | Jan Pohl, Carmen M. Herrera, Steven E. Bosinger, David S. Weiss, Emily K. Crispell, Greg K. Tharp, M. Stephen Trent, Brooke A. Napier, Victor I. Band, Timothy D. Read, Eileen M. Burd, Kranthi Vavikolanu |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Microbiology (medical) Histidine Kinase medicine.drug_class 030106 microbiology Immunology Antibiotics Drug resistance Applied Microbiology and Biotechnology Microbiology Article 03 medical and health sciences Mice Antibiotic resistance Bacterial Proteins Immunity Drug Resistance Multiple Bacterial Enterobacter cloacae Genetics medicine Animals Treatment Failure Innate immune system biology Bacteria Colistin Enterobacteriaceae Infections Cell Biology biochemical phenomena metabolism and nutrition biology.organism_classification Immunity Innate Anti-Bacterial Agents 030104 developmental biology bacteria lipids (amino acids peptides and proteins) medicine.drug |
Zdroj: | Nature microbiology. 1(6) |
ISSN: | 2058-5276 |
Popis: | Antibiotic resistance is a major public health threat, further complicated by unexplained treatment failures caused by bacteria that appear antibiotic susceptible. We describe an Enterobacter cloacae isolate harbouring a minor subpopulation that is highly resistant to the last-line antibiotic colistin. This subpopulation was distinct from persisters, became predominant in colistin, returned to baseline after colistin removal and was dependent on the histidine kinase PhoQ. During murine infection, but in the absence of colistin, innate immune defences led to an increased frequency of the resistant subpopulation, leading to inefficacy of subsequent colistin therapy. An isolate with a lower-frequency colistin-resistant subpopulation similarly caused treatment failure but was misclassified as susceptible by current diagnostics once cultured outside the host. These data demonstrate the ability of low-frequency bacterial subpopulations to contribute to clinically relevant antibiotic resistance, elucidating an enigmatic cause of antibiotic treatment failure and highlighting the critical need for more sensitive diagnostics. |
Databáze: | OpenAIRE |
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