Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study [version 2; peer review: 2 approved]

Background: The effect of sequential exposure to different antibiotics is an underexplored topic. Azithromycin can be detected in humans for up to 28 days post-ingestion and may prime bacterial responses to subsequently ingested antibiotics. Methods: In this in vitro study, we assessed if preexposur...

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Main Authors: Sheeba S. Manoharan–Basil, Saïd Abdellati, Tessa de Block, Natalia González, Irith De Baetselier, Chris Kenyon, Jolein Gyonne Elise Laumen, Christophe Van Dijck
Format: Article
Language:English
Published: F1000 Research Ltd 2023-01-01
Series:F1000Research
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Online Access:https://f1000research.com/articles/11-1464/v2
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author Sheeba S. Manoharan–Basil
Saïd Abdellati
Tessa de Block
Natalia González
Irith De Baetselier
Chris Kenyon
Jolein Gyonne Elise Laumen
Christophe Van Dijck
author_facet Sheeba S. Manoharan–Basil
Saïd Abdellati
Tessa de Block
Natalia González
Irith De Baetselier
Chris Kenyon
Jolein Gyonne Elise Laumen
Christophe Van Dijck
author_sort Sheeba S. Manoharan–Basil
collection DOAJ
description Background: The effect of sequential exposure to different antibiotics is an underexplored topic. Azithromycin can be detected in humans for up to 28 days post-ingestion and may prime bacterial responses to subsequently ingested antibiotics. Methods: In this in vitro study, we assessed if preexposure to azithromycin could accelerate the acquisition of resistance to ciprofloxacin in Neisseria gonorrhoeae reference strain, WHO–F. In a morbidostat, we set two conditions in 3 vials each: mono-exposure (preexposure to Gonococcal Broth followed by exposure to ciprofloxacin) and dual sequential exposure (preexposure to azithromycin followed by exposure to ciprofloxacin).The growth of the cultures was measured by a software (MATLAB). The program decided if gonococcal broth or antibiotics were added to the vials in order to keep the evolution of the cultures. Samples were taken twice a week until the end of the experiment i.e. until resistance was achieved or cellular death. Additionally, six replicates of WHO–F WT and WHO–F with rplV mutation, caused by azithromycin, were exposed to increasing concentrations of ciprofloxacin in plates to assess if there were differences in the rate of resistance emergence. Results: We found that after 12 hours of pre-exposure to azithromycin, N. gonorrhoeae's resilience to ciprofloxacin exposure increased. Pre-exposure to azithromycin did not, however, accelerate the speed to acquisition of ciprofloxacin resistance. Conclusions:  We found that azithromycin does not accelerate the emergence of ciprofloxacin resistance, but there were differences in the molecular pathways to the acquisition of ciprofloxacin resistance: the strains preexpossed to azithromycin followed a different route (GyrA: S91F pathway) than the ones without antibiotic preexposure (GyrA:D95N pathway). However, the number of isolates is too small to draw such strong conclusions.
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spelling doaj.art-7639bc255ba340d596fe03854b332e762023-01-31T01:00:00ZengF1000 Research LtdF1000Research2046-14022023-01-0111143032Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study [version 2; peer review: 2 approved]Sheeba S. Manoharan–Basil0https://orcid.org/0000-0001-8421-5137Saïd Abdellati1https://orcid.org/0000-0002-9620-8257Tessa de Block2Natalia González3https://orcid.org/0000-0003-0999-4315Irith De Baetselier4Chris Kenyon5Jolein Gyonne Elise Laumen6https://orcid.org/0000-0003-0168-5622Christophe Van Dijck7https://orcid.org/0000-0001-8010-1351STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Antwerp, 2000, BelgiumClinical Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Antwerp, 2000, BelgiumClinical Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Antwerp, 2000, BelgiumSTI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Antwerp, 2000, BelgiumClinical Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Antwerp, 2000, BelgiumSTI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Antwerp, 2000, BelgiumSTI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Antwerp, 2000, BelgiumSTI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Antwerp, 2000, BelgiumBackground: The effect of sequential exposure to different antibiotics is an underexplored topic. Azithromycin can be detected in humans for up to 28 days post-ingestion and may prime bacterial responses to subsequently ingested antibiotics. Methods: In this in vitro study, we assessed if preexposure to azithromycin could accelerate the acquisition of resistance to ciprofloxacin in Neisseria gonorrhoeae reference strain, WHO–F. In a morbidostat, we set two conditions in 3 vials each: mono-exposure (preexposure to Gonococcal Broth followed by exposure to ciprofloxacin) and dual sequential exposure (preexposure to azithromycin followed by exposure to ciprofloxacin).The growth of the cultures was measured by a software (MATLAB). The program decided if gonococcal broth or antibiotics were added to the vials in order to keep the evolution of the cultures. Samples were taken twice a week until the end of the experiment i.e. until resistance was achieved or cellular death. Additionally, six replicates of WHO–F WT and WHO–F with rplV mutation, caused by azithromycin, were exposed to increasing concentrations of ciprofloxacin in plates to assess if there were differences in the rate of resistance emergence. Results: We found that after 12 hours of pre-exposure to azithromycin, N. gonorrhoeae's resilience to ciprofloxacin exposure increased. Pre-exposure to azithromycin did not, however, accelerate the speed to acquisition of ciprofloxacin resistance. Conclusions:  We found that azithromycin does not accelerate the emergence of ciprofloxacin resistance, but there were differences in the molecular pathways to the acquisition of ciprofloxacin resistance: the strains preexpossed to azithromycin followed a different route (GyrA: S91F pathway) than the ones without antibiotic preexposure (GyrA:D95N pathway). However, the number of isolates is too small to draw such strong conclusions.https://f1000research.com/articles/11-1464/v2N. gonorrhoeae antimicrobial consumption AMR resistance fluoroquinolone macrolideeng
spellingShingle Sheeba S. Manoharan–Basil
Saïd Abdellati
Tessa de Block
Natalia González
Irith De Baetselier
Chris Kenyon
Jolein Gyonne Elise Laumen
Christophe Van Dijck
Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study [version 2; peer review: 2 approved]
F1000Research
N. gonorrhoeae
antimicrobial consumption
AMR
resistance
fluoroquinolone
macrolide
eng
title Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study [version 2; peer review: 2 approved]
title_full Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study [version 2; peer review: 2 approved]
title_fullStr Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study [version 2; peer review: 2 approved]
title_full_unstemmed Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study [version 2; peer review: 2 approved]
title_short Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study [version 2; peer review: 2 approved]
title_sort pre exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure an in vitro study version 2 peer review 2 approved
topic N. gonorrhoeae
antimicrobial consumption
AMR
resistance
fluoroquinolone
macrolide
eng
url https://f1000research.com/articles/11-1464/v2
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