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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F1000 Research Ltd
2023-01-01
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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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language | English |
last_indexed | 2024-04-10T19:05:38Z |
publishDate | 2023-01-01 |
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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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