Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients

ABSTRACT Fluoroquinolones (FQs) and ciprofloxacin (Cp) are important antimicrobials that pollute the environment in trace amounts. Although Cp has been recommended as prophylaxis for patients undergoing leech therapy to prevent infections by the leech gut symbiont Aeromonas, a puzzling rise in Cp-re...

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Autores principales:	Lidia Beka, Matthew S. Fullmer, Sophie M. Colston, Michael C. Nelson, Emilie Talagrand-Reboul, Paul Walker, Bradley Ford, Iain S. Whitaker, Brigitte Lamy, Johann Peter Gogarten, Joerg Graf
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Aeromonas antibiotic resistance ciprofloxacin leech therapy genomics microbiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ec363db5f23247e58f8bc2c1ada5547d
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spelling	oai:doaj.org-article:ec363db5f23247e58f8bc2c1ada5547d2021-11-15T16:00:15ZLow-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients10.1128/mBio.01328-182150-7511https://doaj.org/article/ec363db5f23247e58f8bc2c1ada5547d2018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01328-18https://doaj.org/toc/2150-7511ABSTRACT Fluoroquinolones (FQs) and ciprofloxacin (Cp) are important antimicrobials that pollute the environment in trace amounts. Although Cp has been recommended as prophylaxis for patients undergoing leech therapy to prevent infections by the leech gut symbiont Aeromonas, a puzzling rise in Cp-resistant (Cpr) Aeromonas infections has been reported. We report on the effects of subtherapeutic FQ concentrations on bacteria in an environmental reservoir, the medicinal leech, and describe the presence of multiple antibiotic resistance mutations and a gain-of-function resistance gene. We link the rise of Cpr Aeromonas isolates to exposure of the leech microbiota to very low levels of Cp (0.01 to 0.04 µg/ml), <1/100 of the clinical resistance breakpoint for Aeromonas. Using competition experiments and comparative genomics of 37 strains, we determined the mechanisms of resistance in clinical and leech-derived Aeromonas isolates, traced their origin, and determined that the presence of merely 0.01 µg/ml Cp provides a strong competitive advantage for Cpr strains. Deep-sequencing the Cpr-conferring region of gyrA enabled tracing of the mutation-harboring Aeromonas population in archived gut samples, and an increase in the frequency of the Cpr-conferring mutation in 2011 coincides with the initial reports of Cpr Aeromonas infections in patients receiving leech therapy. IMPORTANCE The role of subtherapeutic antimicrobial contamination in selecting for resistant strains has received increasing attention and is an important clinical matter. This study describes the relationship of resistant bacteria from the medicinal leech, Hirudo verbana, with patient infections following leech therapy. While our results highlight the need for alternative antibiotic therapies, the rise of Cpr bacteria demonstrates the importance of restricting the exposure of animals to antibiotics approved for veterinary use. The shift to a more resistant community and the dispersion of Cpr-conferring mechanisms via mobile elements occurred in a natural setting due to the presence of very low levels of fluoroquinolones, revealing the challenges of controlling the spread of antibiotic-resistant bacteria and highlighting the importance of a holistic approach in the management of antibiotic use.Lidia BekaMatthew S. FullmerSophie M. ColstonMichael C. NelsonEmilie Talagrand-ReboulPaul WalkerBradley FordIain S. WhitakerBrigitte LamyJohann Peter GogartenJoerg GrafAmerican Society for MicrobiologyarticleAeromonasantibiotic resistanceciprofloxacinleech therapygenomicsmicrobiomeMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aeromonas antibiotic resistance ciprofloxacin leech therapy genomics microbiome Microbiology QR1-502
spellingShingle	Aeromonas antibiotic resistance ciprofloxacin leech therapy genomics microbiome Microbiology QR1-502 Lidia Beka Matthew S. Fullmer Sophie M. Colston Michael C. Nelson Emilie Talagrand-Reboul Paul Walker Bradley Ford Iain S. Whitaker Brigitte Lamy Johann Peter Gogarten Joerg Graf Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients
description	ABSTRACT Fluoroquinolones (FQs) and ciprofloxacin (Cp) are important antimicrobials that pollute the environment in trace amounts. Although Cp has been recommended as prophylaxis for patients undergoing leech therapy to prevent infections by the leech gut symbiont Aeromonas, a puzzling rise in Cp-resistant (Cpr) Aeromonas infections has been reported. We report on the effects of subtherapeutic FQ concentrations on bacteria in an environmental reservoir, the medicinal leech, and describe the presence of multiple antibiotic resistance mutations and a gain-of-function resistance gene. We link the rise of Cpr Aeromonas isolates to exposure of the leech microbiota to very low levels of Cp (0.01 to 0.04 µg/ml), <1/100 of the clinical resistance breakpoint for Aeromonas. Using competition experiments and comparative genomics of 37 strains, we determined the mechanisms of resistance in clinical and leech-derived Aeromonas isolates, traced their origin, and determined that the presence of merely 0.01 µg/ml Cp provides a strong competitive advantage for Cpr strains. Deep-sequencing the Cpr-conferring region of gyrA enabled tracing of the mutation-harboring Aeromonas population in archived gut samples, and an increase in the frequency of the Cpr-conferring mutation in 2011 coincides with the initial reports of Cpr Aeromonas infections in patients receiving leech therapy. IMPORTANCE The role of subtherapeutic antimicrobial contamination in selecting for resistant strains has received increasing attention and is an important clinical matter. This study describes the relationship of resistant bacteria from the medicinal leech, Hirudo verbana, with patient infections following leech therapy. While our results highlight the need for alternative antibiotic therapies, the rise of Cpr bacteria demonstrates the importance of restricting the exposure of animals to antibiotics approved for veterinary use. The shift to a more resistant community and the dispersion of Cpr-conferring mechanisms via mobile elements occurred in a natural setting due to the presence of very low levels of fluoroquinolones, revealing the challenges of controlling the spread of antibiotic-resistant bacteria and highlighting the importance of a holistic approach in the management of antibiotic use.
format	article
author	Lidia Beka Matthew S. Fullmer Sophie M. Colston Michael C. Nelson Emilie Talagrand-Reboul Paul Walker Bradley Ford Iain S. Whitaker Brigitte Lamy Johann Peter Gogarten Joerg Graf
author_facet	Lidia Beka Matthew S. Fullmer Sophie M. Colston Michael C. Nelson Emilie Talagrand-Reboul Paul Walker Bradley Ford Iain S. Whitaker Brigitte Lamy Johann Peter Gogarten Joerg Graf
author_sort	Lidia Beka
title	Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients
title_short	Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients
title_full	Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients
title_fullStr	Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients
title_full_unstemmed	Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients
title_sort	low-level antimicrobials in the medicinal leech select for resistant pathogens that spread to patients
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/ec363db5f23247e58f8bc2c1ada5547d
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Low-Level Antimicrobials in the Medicinal Leech Select for Resistant Pathogens That Spread to Patients

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