8230 Nucleic Acids Research, 2010, Vol. 38, No. 22 5. Gerdes,K., Christensen,S.K. and Løbner-Olesen,A. (2005) Prokaryotic toxin-antitoxin stress response loci. Nat. Rev. Microbiol., 3, 371–382. 6. Tsilibaris,V., Maenhaut-Michel,G., Mine,N. and Van Melderen,L. (2007) What is the beneﬁt to Escherichia coli of having multiple toxin-antitoxin systems in its genome? J. Bacteriol., 189, 6101–6108. 7. Marianovsky,I., Aizenman,E., Engelberg-Kulka,H. and Glaser,G. (2001) The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome. J. Biol. Chem., 276, 5975–5984. 8. Zhang,J., Zhang,Y. and Inouye,M. (2003) Characterization of the interactions within the mazEF addiction module of Escherichia coli. J. Biol. Chem., 278, 32300–32306. 9. Kamada,K., Hanaoka,F. and Burley,S.K. (2003) Crystal structure of the MazE/MazF complex:molecular bases of antidote-toxin recognition. Mol. Cell, 11, 875–884. 10. Zhu,L., Phadtare,S., Nariya,H., Ouyang,M., Husson,R.N. and Inouye,M. (2008) The mRNA interferases, MazF-mt3 and MazF-mt7 from Mycobacterium tuberculosis target unique pentad sequences in single-stranded RNA. Mol. Microbiol., 69, 559–569. 11. Zhang,Y., Zhang,J., Hoeﬂich,K.P., Ikura,M., Qing,G. and Inouye,M. (2003) MazF cleaves cellular mRNAs speciﬁcally at ACA to block protein synthesis in Escherichia coli. Mol. Cell, 12, 913–923. 12. James,P.E., Grinberg,O.Y., Michaels,G. and Swartz,H.M. (1995) Intraphagosomal oxygen in stimulated macrophages. J. Cell Physiol., 163, 241–247. 13. Schaible,U.E., Sturgill-Koszycki,S., Schlesinger,P.H. and Russell,D.G. (1998) Cytokine activation leads to acidiﬁcation and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages. J. Immunol., 160, 1290–1296. 14. Via,L.E., Fratti,R.A., McFalone,M., Pagan-Ramos,E., Deretic,D. and Deretic,V. (1998) Effects of cytokines on mycobacterial phagosome maturation. J. Cell Sci., 111, 897–905. 15. Cole,S.T., Brosch,R., Parkhill,J., Garnier,T., Churcher,C., Harris,D., Gordon,S.V., Eiglmeier,C., Gas,S., Barry,C.E. et al. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature, 393, 537–544. 16. Zhao,L. and Zhang,J. (2008) Biochemical characterization of a chromosomal toxin–antitoxin system in Mycobacterium tuberculosis. FEBS Lett., 582, 710–714. 17. Bhaduri,T., Bagui,T.K., Sikder,D. and Nagaraja,V. (1998) DNA topoisomerase 1 from Mycobacterium smegmatis. An enzyme with distinct features. J. Biol. Chem., 273, 13925–13932. 18. Jain,P. and Nagaraja,V. (2006) Indispensable, functionally complementing N and C-terminal domains constitute site-speciEc topoisomerase I. J. Mol. Biol., 357, 1409–1421. 19. Liu,L.F. and Wang,J.C. (1987) Supercoiling of the DNA template during transcription. Proc. Natl Acad. Sci. USA, 84, 7024–7027. 20. Sassetti,C.M. and Rubin,E.J. (2003) Genetic requirements for mycobacterial survival during infection. Proc. Natl Acad. Sci. USA, 100, 12989–12994. 21. Zhang,L., Zhang,L., Liu,Y., Yang,S., Gao,C., Gong,H., Feng,Y. and He,Z.G. (2009) Archaeal eukaryote-like Orc1/Cdc6 initiators physically interact with DNA polymerase B1 and regulate its functions. Proc. Natl Acad. Sci. USA, 106, 7792–7797. 22. Guo,M., Feng,H., Zhang,J., Wang,W., Li,Y., Gao,C., Chen,H., Feng,Y. and He,Z.G. (2009) Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res., 19, 1301–1308. 23. Cui,T., Zhang,L., Wang,X. and He,Z.G. (2009) Uncovering new signaling proteins and potential drug targets through the interactome analysis of Mycobacterium tuberculosis. BMC Genomics, 10, 118. 24. Gill,S.C. and von Hippel,P.H. (1989) Calculation of protein extinction coefﬁcients from amino acid sequence data. Anal. Biochem., 182, 319–326. 25. Colangeli,R., Helb,D., Vilche` ze,C., Hazbo´ n,M.H., Lee,C.G., Saﬁ,H., Sayers,B., Sardone,I., Jones,M.B. and Fleischmann,R.D. (2007) Transcriptional regulation of multi-drug tolerance and antibiotic-induced responses by the histone-like protein Lsr2 in M. tuberculosis. PLoS Pathog., 3, e87. 26. Grasser,K.D., Ritt,C., Krieg,M., Fernandez,S., Alonso,J.C. and Grimm,R. (1997) The recombinant product of the Chryptomonas phi plastid gene hlpA is an architectural HU-like protein that promotes the assembly of complex nucleoprotein structures. Eur. J. Biochem., 249, 70–76. 27. Bhat,A.G., Leelaram,M.N., Hegde,S.M. and Nagaraja,V. (2009) Deciphering the distinct role for the metal coordination motif in the catalytic activity of Mycobacterium smegmatis topoisomerase I. J. Mol. Biol., 393, 788–802. 28. Ehrt,S., Guo,X.V., Hickey,C.M., Ryou,M., Monteleone,M., Riley,L.W. and Schnappinger,D. (2005) Controlling gene expression in mycobacteria with anhydrotetracycline and Tet repressor. Nucleic Acids Res., 33, e21. 29. Blokpoel,M.C., Murphy,H.N., O’Toole,R., Wiles,S., Runn,E.S., Stewart,G.R., Young,D.B. and Robertson,B.D. (2005) Tetracycline-inducible gene regulation in mycobacteria. Nucleic Acids Res., 33, e22. 30. Gossen,M. and Bujard,H. (1993) Anhydrotetracycline, a novel effector for tetracycline controlled gene expression systems in eukaryotic cells. Nucleic Acids Res., 21, 4411–4412. 31. Keren,I., Kaldalu,N., Spoering,A., Wang,Y. and Lewis,K. (2004) Persister cells and tolerance to antimicrobials. FEMS Microbiol. Lett., 230, 13–18. 32. Spoering,A.L. and Lewis,K. (2001) Bioﬁlms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. J. Bacteriol., 183, 6746–6751. 33. Tse-Dinh,Y.C. (2009) Bacterial topoisomerase I as a target for discovery of antibacterial compounds. Nucleic Acids Res., 37, 731–737. 34. Korch,S.B., Contreras,H. and Clark-Curtiss,J.E. (2009) Three Mycobacterium tuberculosis Rel toxin-antitoxin modules inhibit mycobacterial growth and are expressed in infected human macrophages. J. Bacteriol., 191, 1618–1630. 35. Pruss,G.J. and Drlica,K. (1986) Topoisomerase I mutants: the gene on pBR322 that encodes resistance to tetracycline affects plasmid DNA supercoiling. Proc. Natl Acad. Sci. USA, 83, 8952–8956. 36. Wang,J.C. (1996) DNA topoisomerases. Annu. Rev, Biochem., 65, 635–692. 37. Tse-Dinh,Y.C. (2007) Exploring DNA topoisomerases as targets of novel therapeutic agents in the treatment of infectious diseases. Infect. Disord. Drug Targets, 7, 3–9. 38. Baaklini,I., Usongo,V., Nolent,F., Sanscartier,P., Hraiky,C., Drlica,K. and Drolet,M. (2008) Hypernegative supercoiling inhibits growth by causing RNA degradation. J. Bacteriol., 190, 7346–7356. 39. Drolet,M. (2006) Growth inhibition mediated by excess negative supercoiling: the interplay between transcription elongation, R-loop formation and DNA topology. Mol. Microbiol., 59, 723–730.