title: Disclosure of selective advantages in the "modern" sublineage of the Mycobacterium tuberculosis Beijing genotype family by quantitative proteomics.
abstract: The Mycobacterium tuberculosis Beijing genotype, consisting of the more ancient (atypical) and modern (typical) emerging sublineage, is one of the most prevalent and genetically conserved genotype families and has often been associated with multidrug resistance. In this study, we employed a 2D-LC-FTICR MS approach, combined with dimethylation of tryptic peptides, to systematically compare protein abundance levels of ancient and modern Beijing strains and identify differences that could be associated with successful spread of the modern sublineage. The data is available via ProteomeXchange using the identifier PXD000931. Despite the highly uniform protein abundance ratios in both sublineages, we identified four proteins as differentially regulated between both sublineages, which could explain the apparent increased adaptation of the modern Beijing strains. These proteins are; Rv0450c/MmpL4, Rv1269c, Rv3137, and Rv3283/sseA. Transcriptional and functional analysis of these proteins in a large cohort of 29 Beijing strains showed that the mRNA levels of Rv0450c/MmpL4 are significantly higher in modern Beijing strains, whereas we also provide evidence that Rv3283/sseA is less abundant in the modern Beijing sublineage. Our findings provide a possible explanation for the increased virulence and success of the modern Beijing sublineage. In addition, in the established dataset of 1817 proteins, we demonstrate the pre-existence of several, possibly unique, antibiotic efflux pumps in the proteome of the Beijing strains. This may reflect an increased ability of Beijing strains to escape exposure to antituberculosis drugs.
authors.affiliation: From the ‡Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre (LUMC), Leiden, 2300 RC, The Netherlands; j.de_keijzer@lumc.nl.
authors.forename: Jeroen
authors.initials: J
authors.lastname: de Keijzer
authors.affiliation: §Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, 3720 BA, The Netherlands;
authors.forename: Petra E
authors.initials: PE
authors.lastname: de Haas
authors.affiliation: From the ‡Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre (LUMC), Leiden, 2300 RC, The Netherlands;
authors.forename: Arnoud H
authors.initials: AH
authors.lastname: de Ru
authors.affiliation: From the ‡Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre (LUMC), Leiden, 2300 RC, The Netherlands;
authors.forename: Peter A
authors.initials: PA
authors.lastname: van Veelen
authors.affiliation: §Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, 3720 BA, The Netherlands; ¶Departments of Pulmonary Diseases and Medical Microbiology, Radboud University Medical Centre, Nijmegen, 6500 HB, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: van Soolingen
mesh_terms: D000222:Adaptation, Physiological; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005838:Genotype; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000378:metabolism* / Q000472:pathogenicity; D040901:Proteomics / Q000379:methods*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D037521:Virulence Factors