BibTex format
@article{Boeck:2022:10.1038/s41564-022-01204-x,
author = {Boeck, L and Burbaud, S and Skwark, M and Pearson, WH and Sangen, J and Wuest, AW and Marshall, EKP and Weimann, A and Everall, I and Bryant, JM and Malhotra, S and Bannerman, BP and Kierdorf, K and Blundell, TL and Dionne, MS and Parkhill, J and Floto, RA},
doi = {10.1038/s41564-022-01204-x},
journal = {Nature Microbiology},
pages = {1431--1441},
title = {Mycobacterium abscessus pathogenesis identified by phenogenomic analyses},
url = {http://dx.doi.org/10.1038/s41564-022-01204-x},
volume = {7},
year = {2022}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The medical and scientific response to emerging and established pathogens is often severely hampered by ignorance of the genetic determinants of virulence, drug resistance and clinical outcomes that could be used to identify therapeutic drug targets and forecast patient trajectories. Taking the newly emergent multidrug-resistant bacteria Mycobacterium abscessus as an example, we show that combining high-dimensional phenotyping with whole-genome sequencing in a phenogenomic analysis can rapidly reveal actionable systems-level insights into bacterial pathobiology. Through phenotyping of 331 clinical isolates, we discovered three distinct clusters of isolates, each with different virulence traits and associated with a different clinical outcome. We combined genome-wide association studies with proteome-wide computational structural modelling to define likely causal variants, and employed direct coupling analysis to identify co-evolving, and therefore potentially epistatic, gene networks. We then used in vivo CRISPR-based silencing to validate our findings and discover clinically relevant M. abscessus virulence factors including a secretion system, thus illustrating how phenogenomics can reveal critical pathways within emerging pathogenic bacteria.
AU - Boeck,L
AU - Burbaud,S
AU - Skwark,M
AU - Pearson,WH
AU - Sangen,J
AU - Wuest,AW
AU - Marshall,EKP
AU - Weimann,A
AU - Everall,I
AU - Bryant,JM
AU - Malhotra,S
AU - Bannerman,BP
AU - Kierdorf,K
AU - Blundell,TL
AU - Dionne,MS
AU - Parkhill,J
AU - Floto,RA
DO - 10.1038/s41564-022-01204-x
EP - 1441
PY - 2022///
SN - 2058-5276
SP - 1431
TI - Mycobacterium abscessus pathogenesis identified by phenogenomic analyses
T2 - Nature Microbiology
UR - http://dx.doi.org/10.1038/s41564-022-01204-x
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000844587900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR - https://www.nature.com/articles/s41564-022-01204-x
UR - http://hdl.handle.net/10044/1/115175
VL - 7
ER -
