Antibiotic resistant bacteria survive treatment by doubling while shrinking
ABSTRACT Many antibiotics that are used in healthcare, farming, and aquaculture end up in environments with different spatial structures that might promote heterogeneity in the emergence of antibiotic resistance. However, the experimental evolution of microbes at sub-inhibitory concentrations of ant...
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| Language: | English |
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American Society for Microbiology
2024-12-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02375-24 |
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| author | Adrian Campey Urszula Łapińska Remy Chait Krasimira Tsaneva-Atanasova Stefano Pagliara |
| author_facet | Adrian Campey Urszula Łapińska Remy Chait Krasimira Tsaneva-Atanasova Stefano Pagliara |
| author_sort | Adrian Campey |
| collection | DOAJ |
| description | ABSTRACT Many antibiotics that are used in healthcare, farming, and aquaculture end up in environments with different spatial structures that might promote heterogeneity in the emergence of antibiotic resistance. However, the experimental evolution of microbes at sub-inhibitory concentrations of antibiotics has been mainly carried out at the population level which does not allow capturing single-cell responses to antibiotics. Here, we investigate and compare the emergence of resistance to ciprofloxacin in Escherichia coli in well-mixed and structured environments using experimental evolution, genomics, and microfluidics-based time-lapse microscopy. We discover that resistance to ciprofloxacin and cross-resistance to other antibiotics is stronger in the well-mixed environment due to the emergence of target mutations, whereas efflux regulator mutations emerge in the structured environment. The latter mutants also harbor sub-populations of persisters that survive high concentrations of ciprofloxacin that inhibit bacterial growth at the population level. In contrast, genetically resistant bacteria that display target mutations also survive high concentrations of ciprofloxacin that inhibit their growth via population-level antibiotic tolerance. These resistant and tolerant bacteria keep doubling while shrinking in size in the presence of ciprofloxacin and regain their original size after antibiotic removal, which constitutes a newly discovered phenotypic response. This new knowledge sheds light on the diversity of strategies employed by bacteria to survive antibiotics and poses a stepping stone for understanding the link between mutations at the population level and phenotypic single-cell responses.IMPORTANCEThe evolution of antimicrobial resistance poses a pressing challenge to global health with an estimated 5 million deaths associated with antimicrobial resistance every year globally. Here, we investigate the diversity of strategies employed by bacteria to survive antibiotics. We discovered that bacteria evolve genetic resistance to antibiotics while simultaneously displaying tolerance to very high doses of antibiotics by doubling while shrinking in size. |
| format | Article |
| id | doaj-art-bce3366e16e2425fa91cba48cf6a77a4 |
| institution | OA Journals |
| issn | 2150-7511 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj-art-bce3366e16e2425fa91cba48cf6a77a42025-08-20T02:33:47ZengAmerican Society for MicrobiologymBio2150-75112024-12-01151210.1128/mbio.02375-24Antibiotic resistant bacteria survive treatment by doubling while shrinkingAdrian Campey0Urszula Łapińska1Remy Chait2Krasimira Tsaneva-Atanasova3Stefano Pagliara4Living Systems Institute and Biosciences, University of Exeter, Exeter, Devon, United KingdomLiving Systems Institute and Biosciences, University of Exeter, Exeter, Devon, United KingdomLiving Systems Institute and Biosciences, University of Exeter, Exeter, Devon, United KingdomLiving Systems Institute and Biosciences, University of Exeter, Exeter, Devon, United KingdomLiving Systems Institute and Biosciences, University of Exeter, Exeter, Devon, United KingdomABSTRACT Many antibiotics that are used in healthcare, farming, and aquaculture end up in environments with different spatial structures that might promote heterogeneity in the emergence of antibiotic resistance. However, the experimental evolution of microbes at sub-inhibitory concentrations of antibiotics has been mainly carried out at the population level which does not allow capturing single-cell responses to antibiotics. Here, we investigate and compare the emergence of resistance to ciprofloxacin in Escherichia coli in well-mixed and structured environments using experimental evolution, genomics, and microfluidics-based time-lapse microscopy. We discover that resistance to ciprofloxacin and cross-resistance to other antibiotics is stronger in the well-mixed environment due to the emergence of target mutations, whereas efflux regulator mutations emerge in the structured environment. The latter mutants also harbor sub-populations of persisters that survive high concentrations of ciprofloxacin that inhibit bacterial growth at the population level. In contrast, genetically resistant bacteria that display target mutations also survive high concentrations of ciprofloxacin that inhibit their growth via population-level antibiotic tolerance. These resistant and tolerant bacteria keep doubling while shrinking in size in the presence of ciprofloxacin and regain their original size after antibiotic removal, which constitutes a newly discovered phenotypic response. This new knowledge sheds light on the diversity of strategies employed by bacteria to survive antibiotics and poses a stepping stone for understanding the link between mutations at the population level and phenotypic single-cell responses.IMPORTANCEThe evolution of antimicrobial resistance poses a pressing challenge to global health with an estimated 5 million deaths associated with antimicrobial resistance every year globally. Here, we investigate the diversity of strategies employed by bacteria to survive antibiotics. We discovered that bacteria evolve genetic resistance to antibiotics while simultaneously displaying tolerance to very high doses of antibiotics by doubling while shrinking in size.https://journals.asm.org/doi/10.1128/mbio.02375-24environmental structureantimicrobial resistanceantibiotic toleranceevolutionmutationspersisters |
| spellingShingle | Adrian Campey Urszula Łapińska Remy Chait Krasimira Tsaneva-Atanasova Stefano Pagliara Antibiotic resistant bacteria survive treatment by doubling while shrinking mBio environmental structure antimicrobial resistance antibiotic tolerance evolution mutations persisters |
| title | Antibiotic resistant bacteria survive treatment by doubling while shrinking |
| title_full | Antibiotic resistant bacteria survive treatment by doubling while shrinking |
| title_fullStr | Antibiotic resistant bacteria survive treatment by doubling while shrinking |
| title_full_unstemmed | Antibiotic resistant bacteria survive treatment by doubling while shrinking |
| title_short | Antibiotic resistant bacteria survive treatment by doubling while shrinking |
| title_sort | antibiotic resistant bacteria survive treatment by doubling while shrinking |
| topic | environmental structure antimicrobial resistance antibiotic tolerance evolution mutations persisters |
| url | https://journals.asm.org/doi/10.1128/mbio.02375-24 |
| work_keys_str_mv | AT adriancampey antibioticresistantbacteriasurvivetreatmentbydoublingwhileshrinking AT urszulałapinska antibioticresistantbacteriasurvivetreatmentbydoublingwhileshrinking AT remychait antibioticresistantbacteriasurvivetreatmentbydoublingwhileshrinking AT krasimiratsanevaatanasova antibioticresistantbacteriasurvivetreatmentbydoublingwhileshrinking AT stefanopagliara antibioticresistantbacteriasurvivetreatmentbydoublingwhileshrinking |