Genes required for mycobacterial growth defined by high density mutagenesis
Open accessAbstract
Summary: Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we describe the use of transposon site hybridization (TraSH) to comprehensively identify the genes required by the causative agent, Mycobacterium tuberculosis , for optimal growth. These genes include those that can be assigned to essential pathways as well as many of unknown function. The genes important for the growth of M. tuberculosis are largely conserved in the degenerate genome of the leprosy bacillus, Mycobacterium leprae , indicating that non‐essential functions have been selectively lost since this bacterium diverged from other mycobacteria. In contrast, a surprisingly high proportion of these genes lack identifiable orthologues in other bacteria, suggesting that the minimal gene set required for survival varies greatly between organisms with different evolutionary histories.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Loss of glycosylation in plants, fungi or prokaryotes can also lead to cell death.
“While space does not allow a detailed discussion, loss of glycosylation in plants, fungi or prokaryotes can also lead to cell death.”
From Biological roles of glycans (2017) · cites this paper as [435]
The Discussion reports that genes involved in building the mycobacterial cell wall are required for growth, and Table 2 identifies required steps in rhamnose and mannose metabolism. This supports a related point about prokaryotes, but the paper does not show that loss of glycosylation causes cell death or address plants and fungi. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe F1Fo-ATP synthase is essential for optimal growth in M. tuberculosis and M. smegmatis.
“The F1Fo-ATP synthase in M. tuberculosis and M. smegmatis has been shown to be essential for optimal growth (29, 103).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [29]
The Abstract and Discussion describe a screen for genes required for optimal growth in M. tuberculosis, but the passages found do not identify F1Fo-ATP synthase as one of them. Searches for ATP synthase, atp genes, and M. smegmatis yielded no passage establishing the claimed growth requirement in either species. (LLM, conf=0.74)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence
Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S. V., Eiglmeier, K., Gas, S., Barry, C. E., et al. (1998) · Nature · doi:10.1038/31159 · Cited by 7,847 · see citing works
Massive gene decay in the leprosy bacillus.
Cole, S. T., Eiglmeier, K., Parkhill, J., James, K. D., Thomson, N. R., Wheeler, P. R., Honoré, N., Garnier, T., Churcher, C., Harris, D., et al. (2001) · Nature · doi:10.1038/35059006 · Cited by 1,777 · see citing works
Global Transposon Mutagenesis and a Minimal Mycoplasma Genome
Hutchison, C. A., Peterson, S. N., Gill, S. R., Cline, R. T., White, O. R., Fraser, C. M., Smith, H. O., & Venter, J. C. (1999) · Science · doi:10.1126/science.286.5447.2165 · Cited by 925 · see citing works
Karp, P. D., Paley, S., & Romero, P. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.suppl_1.s225 · Cited by 661 · see citing works
Comprehensive identification of conditionally essential genes in mycobacteria
Sassetti, C. M., Boyd, D. H., & Rubin, E. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231275498 · Cited by 604 · see citing works
Self-citationDe Voss, J. J., Rutter, K., Schroeder, B. G., Su, H., Zhu, Y., & Barry, C. E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.3.1252 · Cited by 532 · see citing works
Rodríguez, G. M., Voskuil, M. I., Gold, B., Schoolnik, G. K., & Smith, I. (2002) · Infection and Immunity · doi:10.1128/iai.70.7.3371-3381.2002 · Cited by 491 · see citing works
A purified mariner transposase is sufficient to mediate transposition in vitro.
Lampe, D. J., Churchill, M. E. A., & Robertson, H. M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00930.x · Cited by 457 · see citing works
Quadri, L. E. N., Sello, J. K., Keating, T. A., Weinreb, P. H., & Walsh, C. T. (1998) · Chemistry & Biology · doi:10.1016/s1074-5521(98)90291-5 · Cited by 417 · see citing works
Ji, Y., Zhang, B., Van, S. F., Horn, Warren, P. V., Woodnutt, G., Burnham, M. K. R., & Rosenberg, M. J. (2001) · Science · doi:10.1126/science.1063566 · Cited by 414 · see citing works
Akerley, B. J., Rubin, E. J., Novick, V. L., Amaya, K. R., Judson, N., & Mekalanos, J. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012602299 · Cited by 358 · see citing works
Self-citationIn vivo transposition of mariner -based elements in enteric bacteria and mycobacteria
Rubin, E. J., Akerley, B. J., Novik, V., Lampe, D. J., Husson, R. N., & Mekalanos, J. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1645 · Cited by 358 · see citing works
Self-citationHyperactive transposase mutants of the Himar 1 mariner transposon
Lampe, D. J., Akerley, B. J., Rubin, E. J., Mekalanos, J. J., & Robertson, H. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11428 · Cited by 281 · see citing works
Self-citationA genome-based approach for the identification of essential bacterial genes
Arigoni, F., Talabot, F., Peitsch, M. C., Edgerton, M. D., Meldrum, E., Allet, E., Fish, R., Jamotte, T., Curchod, M., & Loferer, H. (1998) · Nature Biotechnology · doi:10.1038/nbt0998-851 · Cited by 264 · see citing works
Polarity of Tn5 insertion mutations in Escherichia coli
Berg, D. E., Weiss, A. A., & Crossland, L. D. (1980) · Journal of Bacteriology · doi:10.1128/jb.142.2.439-446.1980 · Cited by 254 · see citing works
An Essential Two-Component Signal Transduction System in Mycobacterium tuberculosis
Zahrt, T. C., & Deretic, V. P. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.13.3832-3838.2000 · Cited by 222 · see citing works
Definition of the First Mannosylation Step in Phosphatidylinositol Mannoside Synthesis
Korduláková, J., Gilleron, M., Mikušová, K., Puzo, G., Brennan, P. J., Gicquel, B., & Jackson, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204060200 · Cited by 192 · see citing works
Pavelka, M. S., & Jacobs, W. R. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.16.4780-4789.1999 · Cited by 177 · see citing works
TnAraOut, A transposon-based approach to identify and characterize essential bacterial genes
Judson, N., & Mekalanos, J. J. (2000) · Nature Biotechnology · doi:10.1038/77305 · Cited by 175 · see citing works
Chalker, A. F., Minehart, H. W., Hughes, N. J., Koretke, K. K., Lonetto, M. A., Brinkman, K. K., Warren, P. V., Lupas, A. N., Stanhope, M. J., Brown, J. R., et al. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.4.1259-1268.2001 · Cited by 157 · see citing works
Biosynthesis of Purine Nucleotides
Buchanan, J. M. (1960) · Elsevier eBooks · doi:10.1016/b978-0-12-395718-4.50013-5 · Cited by 138 · see citing works
whmD is an essential mycobacterial gene required for proper septation and cell division
Gomez, J. E., & Bishai, W. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.140225297 · Cited by 132 · see citing works
Formation of dTDP-Rhamnose Is Essential for Growth of Mycobacteria
Ma, Y., Pan, F., & McNeil, M. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.12.3392-3395.2002 · Cited by 79 · see citing works
Simplified Media for the Growth of Haemophilus influenzae from Clinical and Normal Flora Sources
KLEIN, R. D., & Luginbuhl, G. H. (1979) · Journal of General Microbiology · doi:10.1099/00221287-113-2-409 · Cited by 19 · see citing works
Brennan, P. J., & Vissa, V. (2001) · Leprosy Review · doi:10.5935/0305-7518.20010050 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Varki, A. (2017) · Glycobiology · doi:10.1093/glycob/cww086 · Cited by 2,635 · see citing works
“Knockouts of these genes in mycobacteria are lethal, as is the case with some other glycosyltransferases (435).”
BackgroundThe spectrum of latent tuberculosis: rethinking the biology and intervention strategies
Barry, C. E., Boshoff, H. I., Dartois, V. A., Dick, T., Ehrt, S., Flynn, J. L., Schnappinger, D., Wilkinson, R. J., & Young, D. B. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2236 · Cited by 1,424 · see citing works
Genetic requirements for mycobacterial survival during infection
Sassetti, C. M., & Rubin, E. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2134250100 · Cited by 1,327 · see citing works
Self-citationMycobacterial persistence requires the utilization of host cholesterol
Pandey, A. K., & Sassetti, C. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711159105 · Cited by 1,064 · see citing works
Self-citationGriffin, J. E., Gawronski, J. D., DeJesus, M. A., Ioerger, T. R., Akerley, B. J., & Sassetti, C. M. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002251 · Cited by 1,048 · see citing works
Self-citationvan Opijnen, T., Bodi, K. L., & Camilli, A. (2009) · Nature Methods · doi:10.1038/nmeth.1377 · Cited by 926 · see citing works
The ubiquitin-proteasome system
Nandi, D., Tahiliani, P., Kumar, A., & Chandu, D. (2006) · Journal of Biosciences · doi:10.1007/bf02705243 · Cited by 767 · see citing works
Type VII secretion — mycobacteria show the way
Abdallah, A. M., Gey van Pittius, N. C., DiGiuseppe Champion, P. A., Cox, J., Luirink, J., Vandenbroucke-Grauls, C. M. J. E., Appelmelk, B. J., & Bitter, W. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1773 · Cited by 763 · see citing works
Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved
Comas, I., Chakravartti, J., Small, P. M., Galagan, J. E., Niemann, S., Kremer, K., Ernst, J., & Gagneux, S. (2010) · Nature Genetics · doi:10.1038/ng.590 · Cited by 711 · see citing works
DeJesus, M. A., Gerrick, E. R., Xu, W., Park, S. W., Long, J. E., Boutte, C. C., Rubin, E. J., Schnappinger, D., Ehrt, S., Fortune, S. M., et al. (2017) · mBio · doi:10.1128/mbio.02133-16 · Cited by 676 · see citing works
Self-citationPathogenFinder - Distinguishing Friend from Foe Using Bacterial Whole Genome Sequence Data
Cosentino, S., Larsen, M. V., Aarestrup, F. M., & Lund, O. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077302 · Cited by 675 · see citing works
Pathway to Synthesis and Processing of Mycolic Acids in Mycobacterium tuberculosis
Takayama, K., Wang, C., & Besra, G. S. (2005) · Clinical Microbiology Reviews · doi:10.1128/cmr.18.1.81-101.2005 · Cited by 657 · see citing works
The power to reduce: pyridine nucleotides—small molecules with a multitude of functions
Pollak, N., Dölle, C., & Ziegler, M. (2007) · Biochemical Journal · doi:10.1042/bj20061638 · Cited by 730 · see citing works
Virulence factors of the Mycobacterium tuberculosis complex
Forrellad, M. A., Klepp, L. I., Gioffré, A., y García, J. S., Morbidoni, H. R., Santangelo, M. D. L. P., Cataldi, A. A., & Bigi, F. (2013) · Virulence · doi:10.4161/viru.22329 · Cited by 646 · see citing works
LysM, a widely distributed protein motif for binding to (peptido)glycans
Buist, G., Steen, A., Kok, J., & Kuipers, O. P. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06211.x · Cited by 628 · see citing works
The Transcriptional Responses of Mycobacterium tuberculosis to Inhibitors of Metabolism
Boshoff, H. I., Myers, T. G., Copp, B. R., McNeil, M., Wilson, M. A., & Barry, C. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406796200 · Cited by 609 · see citing works
Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis
Pethe, K., Bifani, P. J., Jang, J., Kang, S., Park, S., Ahn, S., Jiřiček, J., Jung, J., Jeon, H. K., Cechetto, J. D., et al. (2013) · Nature Medicine · doi:10.1038/nm.3262 · Cited by 606 · see citing works
Advanced sequencing technologies: methods and goals
Shendure, J., Mitra, R. D., Varma, C., & Church, G. M. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1325 · Cited by 559 · see citing works
The Proteasome of Mycobacterium tuberculosis Is Required for Resistance to Nitric Oxide
Darwin, K. H., Ehrt, S., Gutierrez-Ramos, J.-C., Weich, N. S., & Nathan, C. (2003) · Science · doi:10.1126/science.1091176 · Cited by 535 · see citing works
Luo, H., Lin, Y., Gao, F., Zhang, C., & Zhang, R. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1131 · Cited by 521 · see citing works
Guinn, K. M., Hickey, M. J., Mathur, S. K., Zakel, K. L., Grotzke, J. E., Lewinsohn, D. M., Smith, S., & Sherman, D. R. (2004) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03844.x · Cited by 508 · see citing works
Tahlan, K., Wilson, R., Kastrinsky, D. B., Arora, K., Nair, V., Fischer, E. R., Barnes, S. W., Walker, J. R., Alland, D., Barry, C. E., et al. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05708-11 · Cited by 501 · see citing works
DEG 5.0, a database of essential genes in both prokaryotes and eukaryotes
Zhang, R., & Lin, Y. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn858 · Cited by 504 · see citing works
Tuberculosis — metabolism and respiration in the absence of growth
Boshoff, H. I. M., & Barry, C. E. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1065 · Cited by 448 · see citing works
Lipoproteins of Bacterial Pathogens
Kovacs-Simon, A., Titball, R. W., & Michell, S. L. (2010) · Infection and Immunity · doi:10.1128/iai.00682-10 · Cited by 441 · see citing works
THE MAGIC BULLETS AND TUBERCULOSIS DRUG TARGETS
Zhang, Y. (2004) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.45.120403.100120 · Cited by 432 · see citing works
van Pittius, N. C. G., Sampson, S. L., Lee, H., Kim, Y., van Helden, P. D., & Warren, R. M. (2006) · BMC Evolutionary Biology · doi:10.1186/1471-2148-6-95 · Cited by 423 · see citing works
Lew, J. M., Kapopoulou, A., Jones, L. M., & Cole, S. T. (2010) · Tuberculosis · doi:10.1016/j.tube.2010.09.008 · Cited by 416 · see citing works
Nathan, C. (2004) · Nature · doi:10.1038/431899a · Cited by 412 · see citing works
Bacterial Growth and Cell Division: a Mycobacterial Perspective
Hett, E. C., & Rubin, E. J. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00028-07 · Cited by 408 · see citing works
Self-citationComparative genomic and phylogeographic analysis of Mycobacterium leprae
Monot, M., Honoré, N., Garnier, T., Zidane, N., Sherafi, D., Paniz‐Mondolfi, A., Matsuoka, M., Taylor, G. M., Donoghue, H. D., Bouwman, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.477 · Cited by 398 · see citing works
Chandrasekaran, S., & Price, N. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005139107 · Cited by 399 · see citing works
Kang, C.-M., Abbott, D. W., Park, S. T., Dascher, C. C., Cantley, L. C., & Husson, R. N. (2005) · Genes & Development · doi:10.1101/gad.1311105 · Cited by 388 · see citing works
ESX secretion systems: mycobacterial evolution to counter host immunity
Gröschel, M. I., Sayes, F., Simeone, R., Majlessi, L., & Brosch, R. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.131 · Cited by 382 · see citing works
NADPH-generating systems in bacteria and archaea
Spaans, S. K., Weusthuis, R. A., John van der, O. O. S. T., & Kengen, S. W. M. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00742 · Cited by 377 · see citing works
Eukaryote-Like Serine/Threonine Kinases and Phosphatases in Bacteria
Pereira, S., Goss, L., & Dworkin, J. (2011) · Microbiology and Molecular Reviews · doi:10.1128/mmbr.00042-10 · Cited by 354 · see citing works
Interplay between mycobacteria and host signalling pathways
Koul, A., Herget, T., Klebl, B., & Ullrich, A. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro840 · Cited by 360 · see citing works
Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis
Bosch, B., DeJesus, M. A., Poulton, N. C., Zhang, W., Engelhart, C. A., Zaveri, A., Lavalette, S., Ruecker, N., Trujillo, C., Wallach, J. B., et al. (2021) · Cell · doi:10.1016/j.cell.2021.06.033 · Cited by 316 · see citing works
Biosynthesis and Functions of Mycothiol, the Unique Protective Thiol of Actinobacteria
Newton, G. L., Buchmeier, N. A., & Fahey, R. C. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00008-08 · Cited by 354 · see citing works
The Bacterial Twin-Arginine Translocation Pathway
Lee, P. A., Tullman‐Ercek, D., & Georgiou, G. (2006) · Annual Review of Microbiology · doi:10.1146/annurev.micro.60.080805.142212 · Cited by 348 · see citing works
Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition
Siegrist, M. S., Unnikrishnan, M., McConnell, M. J., Borowsky, M. L., Cheng, T., Siddiqi, N., Fortune, S. M., Moody, D. B., & Rubin, E. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900589106 · Cited by 329 · see citing works
Self-citationAuranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis
Harbut, M. B., Vilchèze, C., Luo, X., Hensler, M. E., Guo, H., Yang, B., Chatterjee, A. K., Nizet, V., Jacobs, W. R., Schultz, P. G., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1504022112 · Cited by 329 · see citing works
Christophe, T., Jackson, M., Jeon, H. K., Fenistein, D., Contreras-Domínguez, M., Kim, J. C., Genovesio, A., Carralot, J., Ewann, F., Kim, E. H., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000645 · Cited by 324 · see citing works
Mycobacterium tuberculosis nuoG Is a Virulence Gene That Inhibits Apoptosis of Infected Host Cells
Velmurugan, K., Chen, B., Miller, J. L., Azogue, S., Gurses, S. A., Hsu, T., Glickman, M. S., Jacobs, W. R., Porcelli, S. A., & Briken, V. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030110 · Cited by 330 · see citing works
Confronting the scientific obstacles to global control of tuberculosis
Young, D. B., Perkins, M. D., Duncan, K., & Barry, C. E. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34614 · Cited by 324 · see citing works
Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation
Pethe, K., Swenson, D. L., Alonso, S., Anderson, J. L., Wang, C., & Russell, D. G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401657101 · Cited by 318 · see citing works
Chaudhuri, R. R., Allen, A. G., Owen, P., Shalom, G., Stone, K. M., Harrison, M., Burgis, T. A., Lockyer, M. J., Garcı́a-Lara, J., Foster, S. J., et al. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-291 · Cited by 309 · see citing works
Global Transposon Mutagenesis and Essential Gene Analysis of Helicobacter pylori
Salama, N. R., Shepherd, B., & Falkow, S. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.23.7926-7935.2004 · Cited by 309 · see citing works
Systematic Genetic Nomenclature for Type VII Secretion Systems
Bitter, W., Houben, E. N. G., Bottai, D., Brodin, P., Brown, E. J., Cox, J. S., Derbyshire, K., Fortune, S. M., Gao, L.-Y., Liu, J., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000507 · Cited by 307 · see citing works
Self-citationGenomic-scale prioritization of drug targets: the TDR Targets database
Agüero, F., Al‐Lazikani, B., Aslett, M. A., Berriman, M., C, F. S. B. A., Campbell, R. K., Carmona, S. J., Carruthers, I. M., Chan, A. W. E., Chen, F., et al. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2684 · Cited by 306 · see citing works
Supply, P., Marceau, M., Mangenot, S., Roche, D., Rouanet, C., Khanna, V., Majlessi, L., Criscuolo, A., Tap, J., Pawlik, A., et al. (2013) · Nature Genetics · doi:10.1038/ng.2517 · Cited by 305 · see citing works
A Fluoroquinolone Resistance Protein from Mycobacterium tuberculosis That Mimics DNA
Hegde, S. S., Vetting, M. W., Roderick, S. L., Mitchenall, L. A., Maxwell, A., Takiff, H. E., & Blanchard, J. S. (2005) · Science · doi:10.1126/science.1110699 · Cited by 299 · see citing works
Koul, A., Vranckx, L., Dhar, N., Göhlmann, H. W. H., Özdemir, E., Neefs, J., Schulz, M., Lü, P., Mørtz, E., McKinney, J. D., et al. (2014) · Nature Communications · doi:10.1038/ncomms4369 · Cited by 289 · see citing works
Mishra, A. K., Driessen, N. N., Appelmelk, B. J., & Besra, G. S. (2011) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2011.00276.x · Cited by 295 · see citing works
Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs
Weinstein, E. A., Yano, T., Li, L.-S., Avarbock, D., Avarbock, A., Helm, D., McColm, A. A., Duncan, K., Lonsdale, J. T., & Rubin, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500469102 · Cited by 289 · see citing works
Coenzyme A biosynthesis: an antimicrobial drug target
Spry, C., Kirk, K., & Saliba, K. J. (2008) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2007.00093.x · Cited by 293 · see citing works
Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines
Olivares, A. O., Baker, T. A., & Sauer, R. T. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2015.4 · Cited by 292 · see citing works
Raman, K., Yeturu, K., & Chandra, N. R. (2008) · BMC Systems Biology · doi:10.1186/1752-0509-2-109 · Cited by 279 · see citing works
Manson, A. L., Cohen, K. A., Abeel, T., Desjardins, C. A., Armstrong, D. T., Barry, C. E., Brand, J., Chapman, S. B., Cho, S.-N., Gabrielian, A. E., et al. (2017) · Nature Genetics · doi:10.1038/ng.3767 · Cited by 279 · see citing works
Keeping Uracil Out of DNA: Physiological Role, Structure and Catalytic Mechanism of dUTPases
Vértessy, B. G., & Tóth, J. S. (2008) · Accounts of Chemical Research · doi:10.1021/ar800114w · Cited by 273 · see citing works
Abdallah, A. M., Verboom, T., Weerdenburg, E. M., van Pittius, N. C. G., Mahasha, P. W., Jiménez, C. R., Parra, M., Cadieux, N., Brennan, M. J., Appelmelk, B. J., et al. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06783.x · Cited by 268 · see citing works
DEG 15, an update of the Database of Essential Genes that includes built-in analysis tools
Luo, H., Lin, Y., Liu, T., Lai, F.-L., Zhang, C., Gao, F., & Zhang, R. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa917 · Cited by 264 · see citing works
Rohde, K. H., Veiga, D. F. T., Caldwell, S., Balázsi, G., & Russell, D. G. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002769 · Cited by 269 · see citing works
Multiple Toxin-Antitoxin Systems in Mycobacterium tuberculosis
Sala, A. J., Bordes, P., & Genevaux, P. (2014) · Toxins · doi:10.3390/toxins6031002 · Cited by 264 · see citing works
Jamshidi, N., & Palsson, B. Ø. (2007) · BMC Systems Biology · doi:10.1186/1752-0509-1-26 · Cited by 266 · see citing works
Kang, C.-M., Nyayapathy, S., Lee, J.-Y., Suh, J.-W., & Husson, R. N. (2008) · Microbiology · doi:10.1099/mic.0.2007/014076-0 · Cited by 264 · see citing works
Mycobacterial PE/PPE Proteins at the Host-Pathogen Interface
Sampson, S. L. (2011) · Clinical and Developmental Immunology · doi:10.1155/2011/497203 · Cited by 258 · see citing works
Savvi, S., Warner, D. F., Kana, B. D., McKinney, J. D., Mizrahi, V., & Dawes, S. S. (2008) · Journal of Bacteriology · doi:10.1128/jb.01767-07 · Cited by 256 · see citing works
Cowley, S. C., Ko, M., Pick, N., Chow, R., Downing, K. J., Gordhan, B. G., Betts, J. C., Mizrahi, V., Smith, D. A., Stokes, R. W., et al. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04085.x · Cited by 255 · see citing works
TRANSIT - A Software Tool for Himar1 TnSeq Analysis
DeJesus, M. A., Ambadipudi, C., Baker, R., Sassetti, C. M., & Ioerger, T. R. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004401 · Cited by 255 · see citing works
Self-citationGandotra, S., Schnappinger, D., Monteleone, M. M., Hillen, W., & Ehrt, S. (2007) · Nature Medicine · doi:10.1038/nm1683 · Cited by 254 · see citing works
ESX/type VII secretion systems and their role in host–pathogen interaction
Siméone, R., Bottai, D., & Brosch, R. (2009) · Current Opinion in Microbiology · doi:10.1016/j.mib.2008.11.003 · Cited by 250 · see citing works
Fumarate Reductase Activity Maintains an Energized Membrane in Anaerobic Mycobacterium tuberculosis
Watanabe, S., Zimmermann, M., Goodwin, M. B., Sauer, U., Barry, C. E., & Boshoff, H. I. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002287 · Cited by 246 · see citing works
Bacterial proteases, untapped antimicrobial drug targets
Culp, E., & Wright, G. D. (2017) · The Journal of Antibiotics · doi:10.1038/ja.2016.138 · Cited by 244 · see citing works
Global Assessment of Genomic Regions Required for Growth in Mycobacterium tuberculosis
Zhang, Y. J., Ioerger, T. R., Huttenhower, C., Long, J. E., Sassetti, C. M., Sacchettini, J. C., & Rubin, E. J. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002946 · Cited by 242 · see citing works
Self-citationA Comprehensive Genetic Characterization of Bacterial Motility
Girgis, H. S., Liu, Y., Ryu, W. S., & Tavazoie, S. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030154 · Cited by 237 · see citing works
Bhatt, A., Molle, V., Besra, G. S., Jacobs, W. R., & Kremer, L. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05761.x · Cited by 238 · see citing works
A specific secretion system mediates PPE41 transport in pathogenic mycobacteria
Abdallah, A. M., Verboom, T., Hannes, F., Safi, M., Strong, M., Eisenberg, D. S., Musters, R. J. P., Vandenbroucke‐Grauls, C. M. J. E., Appelmelk, B. J., Luirink, J., et al. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05409.x · Cited by 234 · see citing works
Microbial NAD Metabolism: Lessons from Comparative Genomics
Gazzaniga, F., Stebbins, R., Chang, S. Z., McPeek, M. A., & Brenner, C. (2009) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00042-08 · Cited by 230 · see citing works
Lipoproteins in bacteria: structures and biosynthetic pathways
Nakayama, H., Kurokawa, K., & Lee, B. L. (2012) · FEBS Journal · doi:10.1111/febs.12041 · Cited by 231 · see citing works
Essential role of DivIVA in polar growth and morphogenesis in Streptomyces coelicolor A3(2)
Flärdh, K. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03660.x · Cited by 227 · see citing works
Take five — Type VII secretion systems of Mycobacteria
Houben, E. N. G., Korotkov, K. V., & Bitter, W. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.11.003 · Cited by 223 · see citing works
Bald, D., Villellas, C., Lü, P., & Koul, A. (2017) · mBio · doi:10.1128/mbio.00272-17 · Cited by 223 · see citing works
Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria
Cook, G. M., Hards, K., Vilchèze, C., Hartman, T., & Berney, M. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.mgm2-0015-2013 · Cited by 212 · see citing works
“smegmatis has been shown to be essential for optimal growth (29, 103).”
BackgroundStructural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors
Batt, S. M., Jabeen, T., Bhowruth, V., Quill, L., Lund, P. A., Eggeling, L., Alderwick, L. J., Fütterer, K., & Besra, G. S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205735109 · Cited by 220 · see citing works
Knight, M., Braverman, J., Asfaha, K., Gronert, K., & Stanley, S. A. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1006874 · Cited by 219 · see citing works
Portrait of a Pathogen: The Mycobacterium tuberculosis Proteome In Vivo
Kruh, N. A., Troudt, J., Izzo, A., Prenni, J., & Dobos, K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013938 · Cited by 213 · see citing works
Niebisch, A., Kabus, A., Schultz, C., Weil, B., & Bott, M. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512515200 · Cited by 217 · see citing works
Redox homeostasis in mycobacteria: the key to tuberculosis control?
Kumar, A., Farhana, A., Guidry, L., Saini, V., Hondalus, M. K., & Steyn, A. J. C. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411002079 · Cited by 206 · see citing works
Almeida, D. V., Ioerger, T. R., Tyagi, S. K., Li, S., Mdluli, K. E., Andries, K., Grosset, J. H. E., Sacchettini, J. C., & Nuermberger, E. L. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00753-16 · Cited by 210 · see citing works
Sweeney, K. A., Dao, D. N., Goldberg, M. F., Hsu, T., Venkataswamy, M. M., Henao-Tamayo, M. I., Ordway, D. J., Sellers, R. S., Jain, P., Chen, B., et al. (2011) · Nature Medicine · doi:10.1038/nm.2420 · Cited by 208 · see citing works
GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosismetabolism
Beste, D. J. V., Hooper, T., Stewart, G. R., Bonde, B. K., Avignone-Rossa, C. A., Bushell, M. E., Wheeler, P. R., Klamt, S., Kierzek, A. M., & McFadden, J. (2007) · Genome biology · doi:10.1186/gb-2007-8-5-r89 · Cited by 204 · see citing works
Cook, G. M., Berney, M., Gebhard, S., Heinemann, M., Cox, R. A., Danilchanka, O., & Niederweis, M. (2009) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/s0065-2911(09)05502-7 · Cited by 205 · see citing works
The Key Role of Genomics in Modern Vaccine and Drug Design for Emerging Infectious Diseases
Seib, K. L., Gordon Dougan, B., & Rappuoli, R. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000612 · Cited by 203 · see citing works
Berg, S., Kaur, D., Jackson, M., & Brennan, P. J. (2007) · Glycobiology · doi:10.1093/glycob/cwm010 · Cited by 202 · see citing works
The Toxin-Antitoxin System DarTG Catalyzes Reversible ADP-Ribosylation of DNA
Jankevicius, G., Ariza, A., Ahel, M., & Ahel, I. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.11.014 · Cited by 196 · see citing works
Bacterial Branched-Chain Amino Acid Biosynthesis: Structures, Mechanisms, and Drugability
Franco, T. M. A., & Blanchard, J. S. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00849 · Cited by 202 · see citing works
Serafini, A., Boldrin, F., Palù, G., & Manganelli, R. (2009) · Journal of Bacteriology · doi:10.1128/jb.00756-09 · Cited by 198 · see citing works
Tian, J., Bryk, R., Itoh, M., Suematsu, M., & Nathan, C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501605102 · Cited by 200 · see citing works
Zheng, J., Rubin, E. J., Bifani, P. J., Mathys, V., Lim, V., Au, M., Jang, J., Nam, J., Dick, T., Walker, J. R., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.475798 · Cited by 199 · see citing works
Self-citation
- Authors
- Sassetti, C. M., Boyd, D. H., & Rubin, E. J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Rubin, Eric J.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2003-03-25
- Volume
- 48
- Issue
- 1
- Pages
- 77-84
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2128482141
- Cited by
- 2,544
- References
- 25
- Citations by year
- 2026: 43 · 2025: 71 · 2024: 99 · 2023: 77 · 2022: 87 · 2021: 94 · 2020: 114 · 2019: 137 · 2018: 111 · 2017: 129 · 2016: 129 · 2015: 154 · 2014: 149 · 2013: 154 · 2012: 128
- FWCI
- 45.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI 48704, R01AI048704, R01AI051929, AI51929)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- Mycobacterium tuberculosis, Mycobacterium leprae, essential genes, bacterial growth, gene essentiality, drug resistance, gene loss, minimal gene set, orthologs
- MeSH terms
- DNA Transposable Elements, Genes, Bacterial, Mycobacterium leprae, Mycobacterium tuberculosis, Mutagenesis, Evolution, Molecular
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
