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

Autor:	Wang K; Department of Respiratory Disease, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.; Centre for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China., Chen YQ; Department of Respiratory Disease, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China chenyq0708@foxmail.com., Salido MM; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore., Kohli GS; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore., Kong JL; Department of Respiratory Disease, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China., Liang HJ; Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China., Yao ZT; Centre for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China., Xie YT; The First Clinical School of Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China., Wu HY; Department of Cell Biology and Genetics, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China., Cai SQ; Department of Respiratory Disease, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China., Drautz-Moses DI; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore., Darling AE; The ithree Institute, University of Technology Sydney, Sydney, New South Wales, Australia., Schuster SC; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore., Yang L; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore., Ding Y; Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore di0001en@e.ntu.edu.sg.; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.; Interdisciplinary Graduate School, SCELSE, Nanyang Technological University, Singapore 639798, Singapore.
Jazyk:	angličtina
Zdroj:	Open biology [Open Biol] 2017 Sep; Vol. 7 (9).
DOI:	10.1098/rsob.170029
Abstrakt:	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. (© 2017 The Authors.)
Databáze:	MEDLINE
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