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L-form switching confers antibiotic, phage and stress tolerance in pathogenic Escherichia coli

View ORCID ProfileAleksandra Petrovic Fabijan, Muhammad Kamruzzaman, David Martinez-Martin, Carola Venturini, Katarzyna Mickiewicz, Neftali Flores-Rodriguez, Jeff Errington, Jonathan R. Iredell
doi: https://doi.org/10.1101/2021.06.21.449206
Aleksandra Petrovic Fabijan
1Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Sydney, New South Wales, Australia
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  • ORCID record for Aleksandra Petrovic Fabijan
Muhammad Kamruzzaman
1Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Sydney, New South Wales, Australia
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David Martinez-Martin
2School of Biomedical Engineering, The University of Sydney, Sydney, New South Wales, Australia
3The University of Sydney Nano Institute, The University of Sydney, Sydney, New South Wales 2006, Australia
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Carola Venturini
1Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Sydney, New South Wales, Australia
4School of Medicine, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
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Katarzyna Mickiewicz
5Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
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Neftali Flores-Rodriguez
6Sydney Microscopy and Microanalysis, Charles Perkins, The University of Sydney, Sydney, New South Wales, Australia
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Jeff Errington
5Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom
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Jonathan R. Iredell
1Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Sydney, New South Wales, Australia
4School of Medicine, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
7Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
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Abstract

The bacterial L-form is induced by exposure to cell wall targeting antibiotics or innate immune effectors such as lysozyme and is likely to be important in many human infections. Here, we demonstrate that the osmotically fragile L-form is a distinct physiological state in Escherichia coli that is highly tolerant of oxidative stress and resistant to powerful antibiotics and common therapeutic bacteriophages. L-forms quickly revert (<20h) to their cell-walled state after antibiotic withdrawal, with apparently normal physiology and with few or no changes in DNA sequence. T4-like phages that are obligately lytic in cell-walled E. coli preferentially pseudolysogenise their L-forms providing them with transient superinfection immunity. Our data indicate that L-form switching is a common response of pathogenic E. coli strains to cell wall-targeting antibiotics and that the most commonly used lytic bacteriophages are ineffective against them in this state.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 21, 2021.
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L-form switching confers antibiotic, phage and stress tolerance in pathogenic Escherichia coli
Aleksandra Petrovic Fabijan, Muhammad Kamruzzaman, David Martinez-Martin, Carola Venturini, Katarzyna Mickiewicz, Neftali Flores-Rodriguez, Jeff Errington, Jonathan R. Iredell
bioRxiv 2021.06.21.449206; doi: https://doi.org/10.1101/2021.06.21.449206
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L-form switching confers antibiotic, phage and stress tolerance in pathogenic Escherichia coli
Aleksandra Petrovic Fabijan, Muhammad Kamruzzaman, David Martinez-Martin, Carola Venturini, Katarzyna Mickiewicz, Neftali Flores-Rodriguez, Jeff Errington, Jonathan R. Iredell
bioRxiv 2021.06.21.449206; doi: https://doi.org/10.1101/2021.06.21.449206

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