PXD013677

PXD013677 is an original dataset announced via ProteomeXchange.

Title	A safe alternative to H37Rv: the attenuated double auxotroph Mycobacterium tuberculosis ΔleuDΔpanCD
Description	Currently available model organisms such as Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) have significantly contributed to our understanding of tuberculosis (TB) biology, these models have limitations such as differences in genome size, growth rates and virulence. Attenuated Mycobacterium tuberculosis strains may provide more representative, safer models to study M. tuberculosis biology. For example, the M. tuberculosis ΔleuDΔpanCD double auxotroph, has undergone rigorous in vitro and in vivo safety testing. Like other auxotrophic strains, this has subsequently been approved for use in biosafety level (BSL) 2 facilities. Auxotrophic strains have been assessed as models for drug-resistant M. tuberculosis and for studying latent TB. These offer the potential as safe and useful models, but it is important to understand how well these recapitulate salient features of non-attenuated M. tuberculosis. We therefore performed a comprehensive comparison of M. tuberculosis H37Rv and M. tuberculosis ΔleuDΔpanCD. These strains demonstrated similar in vitro and intra-macrophage replication rates, similar responses to anti-TB agents and whole genome sequence conservation. Shotgun proteomics analysis suggested that M. tuberculosis ΔleuDΔpanCD has an increased propensity to enter a dormant state during acid stress, which has been verified using a dual-fluorescent replication reporter assay. Importantly, infection of human peripheral blood mononuclear cells with the 2 strains elicited comparable cytokine production, demonstrating the suitability of M. tuberculosis ΔleuDΔpanCD for immunological assays. We provide comprehensive evidence to support the judicious use of M. tuberculosis ΔleuDΔpanCD as a safe and suitable model organism for M. tuberculosis research, without the need for a BSL3 facility.
HostingRepository	PRIDE
AnnounceDate	2019-10-10
AnnouncementXML	Submission_2019-10-11_02:50:24.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Samantha Sampson
SpeciesList	scientific name: Mycobacterium tuberculosis; NCBI TaxID: 1773;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-30 08:05:59	ID requested
1	2019-07-30 02:23:40	announced
2	2019-10-10 08:44:21	announced	2019-10-10: Updated project metadata.
⏵ 3	2019-10-11 02:50:25	announced	2019-10-10: Updated project metadata. 2019-10-11: Updated publication reference for PubMed record(s): 31481950.

Mouton JM, Heunis T, Dippenaar A, Gallant JL, Kleynhans L, Sampson SL, as an Alternative to H37Rv. Front Microbiol, 10():1922(2019) [pubmed]

submitter keyword: Mycobacterium tuberculosis, model organism, attenuated auxotroph, biosafety level 2

Samantha L. Sampson
contact affiliation	DST/NRF Centre of Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
contact email	ssampson@sun.ac.za
lab head
Samantha Sampson
contact affiliation	Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town
contact email	ssampson@sun.ac.za
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013677
     1. Label: PRIDE project
     2. Name: A safe alternative to H37Rv: the attenuated double auxotroph Mycobacterium tuberculosis ΔleuDΔpanCD