Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates

ABSTRACT The spread of antibiotic resistance is driving interest in new approaches to control bacterial pathogens. This includes applying multiple antibiotics strategically, using bacteriophages against antibiotic-resistant bacteria, and combining both types of antibacterial agents. All these approa...

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Autores principales:	Richard C. Allen, Katia R. Pfrunder-Cardozo, Dominik Meinel, Adrian Egli, Alex R. Hall
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Escherichia coli antibiotic resistance bacteriophages evolution microbial ecology plasmids Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6d8b99b4384b4481b40a251d34c91fe8
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spelling	oai:doaj.org-article:6d8b99b4384b4481b40a251d34c91fe82021-11-15T15:51:51ZAssociations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates10.1128/mBio.01341-172150-7511https://doaj.org/article/6d8b99b4384b4481b40a251d34c91fe82017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01341-17https://doaj.org/toc/2150-7511ABSTRACT The spread of antibiotic resistance is driving interest in new approaches to control bacterial pathogens. This includes applying multiple antibiotics strategically, using bacteriophages against antibiotic-resistant bacteria, and combining both types of antibacterial agents. All these approaches rely on or are impacted by associations among resistance phenotypes (where bacteria resistant to one antibacterial agent are also relatively susceptible or resistant to others). Experiments with laboratory strains have shown strong associations between some resistance phenotypes, but we lack a quantitative understanding of associations among antibiotic and phage resistance phenotypes in natural and clinical populations. To address this, we measured resistance to various antibiotics and bacteriophages for 94 natural and clinical Escherichia coli isolates. We found several positive associations between resistance phenotypes across isolates. Associations were on average stronger for antibacterial agents of the same type (antibiotic-antibiotic or phage-phage) than different types (antibiotic-phage). Plasmid profiles and genetic knockouts suggested that such associations can result from both colocalization of resistance genes and pleiotropic effects of individual resistance mechanisms, including one case of antibiotic-phage cross-resistance. Antibiotic resistance was predicted by core genome phylogeny and plasmid profile, but phage resistance was predicted only by core genome phylogeny. Finally, we used observed associations to predict genes involved in a previously uncharacterized phage resistance mechanism, which we verified using experimental evolution. Our data suggest that susceptibility to phages and antibiotics are evolving largely independently, and unlike in experiments with lab strains, negative associations between antibiotic resistance phenotypes in nature are rare. This is relevant for treatment scenarios where bacteria encounter multiple antibacterial agents. IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages.Richard C. AllenKatia R. Pfrunder-CardozoDominik MeinelAdrian EgliAlex R. HallAmerican Society for MicrobiologyarticleEscherichia coliantibiotic resistancebacteriophagesevolutionmicrobial ecologyplasmidsMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Escherichia coli antibiotic resistance bacteriophages evolution microbial ecology plasmids Microbiology QR1-502
spellingShingle	Escherichia coli antibiotic resistance bacteriophages evolution microbial ecology plasmids Microbiology QR1-502 Richard C. Allen Katia R. Pfrunder-Cardozo Dominik Meinel Adrian Egli Alex R. Hall Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates
description	ABSTRACT The spread of antibiotic resistance is driving interest in new approaches to control bacterial pathogens. This includes applying multiple antibiotics strategically, using bacteriophages against antibiotic-resistant bacteria, and combining both types of antibacterial agents. All these approaches rely on or are impacted by associations among resistance phenotypes (where bacteria resistant to one antibacterial agent are also relatively susceptible or resistant to others). Experiments with laboratory strains have shown strong associations between some resistance phenotypes, but we lack a quantitative understanding of associations among antibiotic and phage resistance phenotypes in natural and clinical populations. To address this, we measured resistance to various antibiotics and bacteriophages for 94 natural and clinical Escherichia coli isolates. We found several positive associations between resistance phenotypes across isolates. Associations were on average stronger for antibacterial agents of the same type (antibiotic-antibiotic or phage-phage) than different types (antibiotic-phage). Plasmid profiles and genetic knockouts suggested that such associations can result from both colocalization of resistance genes and pleiotropic effects of individual resistance mechanisms, including one case of antibiotic-phage cross-resistance. Antibiotic resistance was predicted by core genome phylogeny and plasmid profile, but phage resistance was predicted only by core genome phylogeny. Finally, we used observed associations to predict genes involved in a previously uncharacterized phage resistance mechanism, which we verified using experimental evolution. Our data suggest that susceptibility to phages and antibiotics are evolving largely independently, and unlike in experiments with lab strains, negative associations between antibiotic resistance phenotypes in nature are rare. This is relevant for treatment scenarios where bacteria encounter multiple antibacterial agents. IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages.
format	article
author	Richard C. Allen Katia R. Pfrunder-Cardozo Dominik Meinel Adrian Egli Alex R. Hall
author_facet	Richard C. Allen Katia R. Pfrunder-Cardozo Dominik Meinel Adrian Egli Alex R. Hall
author_sort	Richard C. Allen
title	Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates
title_short	Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates
title_full	Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates
title_fullStr	Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates
title_full_unstemmed	Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates
title_sort	associations among antibiotic and phage resistance phenotypes in natural and clinical <italic toggle="yes">escherichia coli</italic> isolates
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/6d8b99b4384b4481b40a251d34c91fe8
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Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical <italic toggle="yes">Escherichia coli</italic> Isolates

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