Cell population heterogeneity in Mycobacterium tuberculosis H37Rv

被引:17
作者
Andreu, Nuria [1 ]
Gibert, Isidre [1 ,2 ]
机构
[1] Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
[2] Univ Autonoma Barcelona, Fac Biociencies, Dept Genet & Microbiol, E-08193 Barcelona, Spain
基金
英国惠康基金;
关键词
Neutral red; Phthiocerol dimycocerosates; Phenotypic variation; Virulence instability; Population heterogeneity;
D O I
10.1016/j.tube.2008.03.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The laboratory strain H37Rv represents one of the most commonly used strains in the study of Mycobacterium tuberculosis. Despite the apparent stability of the strain, the absence of a selective pressure for virulence factors could lead to the in vitro accumulation of attenuated mutants. To assess this hypothesis, we performed a systematic analysis of individual clones isolated from subcultured M. tuberculosis H37Rv and from a non-subcultured frozen stock. First, we studied two virulence indicators: neutral red staining and content of phthiocerol dimyco-cerosates (PDIMs). We found that H37Rv formed a mixed population containing wild-type cells, as well as neutral red and PDIM mutants. Then, we compared the global gene expression of 3 isolated clones (which displayed various phenotypes) and the non-subcultured stock, by micro-array analysis. This transcriptional profiting confirmed that a significant heterogeneity existed despite, and in addition to, the neutral red and PDIM phenotypes. These results strongly suggest that great caution must be taken in extrapolating data obtained with M. tuberculosis H37Rv grown in vitro, and it would be prudent to study several independent clones to obtain valid conclusions. For this purpose, the neutral red and PDIM phenotypes might be useful indicators of undesired heterogeneity. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:553 / 559
页数:7
相关论文
共 31 条
[1]   Targeted replacement of the mycocerosic acid synthase gene in Mycobacterium bovis BCG produces a mutant that lacks mycosides [J].
Azad, AK ;
Sirakova, TD ;
Rogers, LM ;
Kolattukudy, PE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (10) :4787-4792
[2]   Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis [J].
Camacho, LR ;
Ensergueix, D ;
Perez, E ;
Gicquel, B ;
Guilhot, C .
MOLECULAR MICROBIOLOGY, 1999, 34 (02) :257-267
[3]   Neutral-red reaction is related to virulence and cell wall methyl-branched lipids in Mycobacterium tuberculosis [J].
Cardona, PJ ;
Soto, CY ;
Martín, C ;
Giquel, B ;
Agustí, G ;
Andreu, N ;
Guirado, E ;
Sirakova, T ;
Kolattukudy, R ;
Julián, E ;
Luquin, M .
MICROBES AND INFECTION, 2006, 8 (01) :183-190
[4]   Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence [J].
Cole, ST ;
Brosch, R ;
Parkhill, J ;
Garnier, T ;
Churcher, C ;
Harris, D ;
Gordon, SV ;
Eiglmeier, K ;
Gas, S ;
Barry, CE ;
Tekaia, F ;
Badcock, K ;
Basham, D ;
Brown, D ;
Chillingworth, T ;
Connor, R ;
Davies, R ;
Devlin, K ;
Feltwell, T ;
Gentles, S ;
Hamlin, N ;
Holroyd, S ;
Hornby, T ;
Jagels, K ;
Krogh, A ;
McLean, J ;
Moule, S ;
Murphy, L ;
Oliver, K ;
Osborne, J ;
Quail, MA ;
Rajandream, MA ;
Rogers, J ;
Rutter, S ;
Seeger, K ;
Skelton, J ;
Squares, R ;
Squares, S ;
Sulston, JE ;
Taylor, K ;
Whitehead, S ;
Barrell, BG .
NATURE, 1998, 393 (6685) :537-+
[5]   Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex -: Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene [J].
Constant, P ;
Perez, E ;
Malaga, W ;
Lanéelle, MA ;
Saurel, O ;
Daffé, M ;
Guilhot, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (41) :38148-38158
[6]   Complex lipid determine tissue specific replication of Mycobacterium tuberculosis in mice [J].
Cox, JS ;
Chen, B ;
McNeil, M ;
Jacobs, WR .
NATURE, 1999, 402 (6757) :79-83
[7]  
DOBSON G, 1985, CHEM METHODS BACTERI, V1, P237
[8]   The role of MmpL8 in sulfatide biogenesis and virulence of Mycobacterium tuberculosis [J].
Domenech, P ;
Reed, MB ;
Dowd, CS ;
Manca, C ;
Kaplan, G ;
Barry, CE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (20) :21257-21265
[9]  
DUBOS RJ, 1948, AM REV TUBERC PULM, V58, P698
[10]  
FOLCH J, 1957, J BIOL CHEM, V226, P497