The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe airway infections in humans. These infections are usually difficult to treat and associated with high mortality rates. While colonizing the human airways, P. aeruginosa could accumulate genetic mutations that often lead to its be...

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Main Authors: Wang, Ke, Chen, Yi-qiang, Salido, May M., Kohli, Gurjeet S., Kong, Jin-liang, Liang, Hong-jie, Yao, Zi-ting, Xie, Yan-tong, Wu, Hua-yu, Cai, Shuang-qi, Drautz-Moses, Daniela I., Darling, Aaron E., Schuster, Stephan C., Yang, Liang, Ding, Yichen
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/85357
http://hdl.handle.net/10220/48202
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-853572020-09-21T11:34:39Z The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence Wang, Ke Chen, Yi-qiang Salido, May M. Kohli, Gurjeet S. Kong, Jin-liang Liang, Hong-jie Yao, Zi-ting Xie, Yan-tong Wu, Hua-yu Cai, Shuang-qi Drautz-Moses, Daniela I. Darling, Aaron E. Schuster, Stephan C. Yang, Liang Ding, Yichen School of Biological Sciences Interdisciplinary Graduate School (IGS) Singapore Centre for Environmental Life Sciences and Engineering Pseudomonas Aeruginosa Ventilator-associated Pneumonia DRNTU::Engineering::Environmental engineering Pseudomonas aeruginosa is an opportunistic pathogen that causes severe airway infections in humans. These infections are usually difficult to treat and associated with high mortality rates. While colonizing the human airways, P. aeruginosa could accumulate genetic mutations that often lead to its better adaptability to the host environment. Understanding these evolutionary traits may provide important clues for the development of effective therapies to treat P. aeruginosa infections. In this study, 25 P. aeruginosa isolates were longitudinally sampled from the airways of four ventilator-associated pneumonia (VAP) patients. Pacbio and Illumina sequencing were used to analyse the in vivo evolutionary trajectories of these isolates. Our analysis showed that positive selection dominantly shaped P. aeruginosa genomes during VAP infections and led to three convergent evolution events, including loss-of-function mutations of lasR and mpl, and a pyoverdine-deficient phenotype. Specifically, lasR encodes one of the major transcriptional regulators in quorum sensing, whereas mpl encodes an enzyme responsible for recycling cell wall peptidoglycan. We also found that P. aeruginosa isolated at late stages of VAP infections produce less elastase and are less virulent in vivo than their earlier isolated counterparts, suggesting the short-term in vivo evolution of P. aeruginosa leads to attenuated virulence. MOE (Min. of Education, S’pore) Published version 2019-05-15T03:17:10Z 2019-12-06T16:02:22Z 2019-05-15T03:17:10Z 2019-12-06T16:02:22Z 2017 Journal Article Wang, K., Chen, Y., Salido, M. M., Kohli, G. S., Kong, J., Liang, H., . . . Ding, Y. (2017). The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence. Open Biology, 7(9), 170029-. doi:10.1098/rsob.170029 https://hdl.handle.net/10356/85357 http://hdl.handle.net/10220/48202 10.1098/rsob.170029 en Open Biology © 2017 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the originalauthor and source are credited 13 p. application/pdf
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic Pseudomonas Aeruginosa
Ventilator-associated Pneumonia
DRNTU::Engineering::Environmental engineering
spellingShingle Pseudomonas Aeruginosa
Ventilator-associated Pneumonia
DRNTU::Engineering::Environmental engineering
Wang, Ke
Chen, Yi-qiang
Salido, May M.
Kohli, Gurjeet S.
Kong, Jin-liang
Liang, Hong-jie
Yao, Zi-ting
Xie, Yan-tong
Wu, Hua-yu
Cai, Shuang-qi
Drautz-Moses, Daniela I.
Darling, Aaron E.
Schuster, Stephan C.
Yang, Liang
Ding, Yichen
The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence
description Pseudomonas aeruginosa is an opportunistic pathogen that causes severe airway infections in humans. These infections are usually difficult to treat and associated with high mortality rates. While colonizing the human airways, P. aeruginosa could accumulate genetic mutations that often lead to its better adaptability to the host environment. Understanding these evolutionary traits may provide important clues for the development of effective therapies to treat P. aeruginosa infections. In this study, 25 P. aeruginosa isolates were longitudinally sampled from the airways of four ventilator-associated pneumonia (VAP) patients. Pacbio and Illumina sequencing were used to analyse the in vivo evolutionary trajectories of these isolates. Our analysis showed that positive selection dominantly shaped P. aeruginosa genomes during VAP infections and led to three convergent evolution events, including loss-of-function mutations of lasR and mpl, and a pyoverdine-deficient phenotype. Specifically, lasR encodes one of the major transcriptional regulators in quorum sensing, whereas mpl encodes an enzyme responsible for recycling cell wall peptidoglycan. We also found that P. aeruginosa isolated at late stages of VAP infections produce less elastase and are less virulent in vivo than their earlier isolated counterparts, suggesting the short-term in vivo evolution of P. aeruginosa leads to attenuated virulence.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Wang, Ke
Chen, Yi-qiang
Salido, May M.
Kohli, Gurjeet S.
Kong, Jin-liang
Liang, Hong-jie
Yao, Zi-ting
Xie, Yan-tong
Wu, Hua-yu
Cai, Shuang-qi
Drautz-Moses, Daniela I.
Darling, Aaron E.
Schuster, Stephan C.
Yang, Liang
Ding, Yichen
format Article
author Wang, Ke
Chen, Yi-qiang
Salido, May M.
Kohli, Gurjeet S.
Kong, Jin-liang
Liang, Hong-jie
Yao, Zi-ting
Xie, Yan-tong
Wu, Hua-yu
Cai, Shuang-qi
Drautz-Moses, Daniela I.
Darling, Aaron E.
Schuster, Stephan C.
Yang, Liang
Ding, Yichen
author_sort Wang, Ke
title The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence
title_short The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence
title_full The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence
title_fullStr The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence
title_full_unstemmed The rapid in vivo evolution of Pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence
title_sort rapid in vivo evolution of pseudomonas aeruginosa in ventilator-associated pneumonia patients leads to attenuated virulence
publishDate 2019
url https://hdl.handle.net/10356/85357
http://hdl.handle.net/10220/48202
_version_ 1681058393620480000