Persisters, persistent infections and the Yin-Yang model

Emerging Microbes and Infections

Volumn 3, Issue , 2014, Pages

  Zhang, Ying ^a,b  

^a JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

^b FUDAN UNIVERSITY   (China)

Author keywords

mechanisms; persistence; persisters; treatment strategies

Indexed keywords

AMOXICILLIN; ANTIBIOTIC AGENT; AZITHROMYCIN; BISMUTH; DNA BINDING PROTEIN; DOXYCYCLINE; ETHAMBUTOL; ISONIAZID; MACROLIDE; PENICILLIN DERIVATIVE; PROTEIN SYNTHESIS INHIBITOR; PYRAZINAMIDE; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RIFAMPICIN; TETRACYCLINE; VANCOMYCIN;

ALTERNATIVE ENERGY; ANTIBIOTIC THERAPY; BACTERIAL SURVIVAL; BRUCELLA ABORTUS; CANCER STEM CELL; CFU COUNTING; CHINESE MEDICINE; DRUG TOLERANCE; EFFUSION; ENERGY YIELD; ESCHERICHIA COLI; GENETIC RESISTANCE; HUMAN; LATENT TUBERCULOSIS; MACROMOLECULE; MUTAGENESIS; MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PATHOGENESIS; PERSISTENT INFECTION; PHOSPHATE METABOLISM; PRIORITY JOURNAL; PSEUDOMONAS INFECTION; REVIEW; SINGLE CELL ANALYSIS;

EID: 84892188759     PISSN: None     EISSN: 22221751     Source Type: Journal    
DOI: 10.1038/emi.2014.3     Document Type: Review

References (125)

1. Hobby GL, Meyer K, Chaffee E. Observations on the mechanism of action of penicillin. Proc Soc Exp Biol NY 1942; 50: 281-285.
2. Bigger JW. Treatment of staphylococcal infections with penicillin by intermittent sterilisation. Lancet 1944; 244: 497-500.
3. Moyed HS, Bertrand KP. hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis. J Bacteriol 1983; 155: 768-775. (Pubitemid 13048115)
4. Li Y, Zhang Y. PhoU is a persistence switch involved in persister formation and tolerance to multiple antibiotics and stresses in Escherichia coli. Antimicrob Agents Chemother 2007; 51: 2092-2099. (Pubitemid 46903099)
5. Zhang Y. Advances in the treatment of tuberculosis. Clin Pharmacol Ther 2007; 82: 595-600. (Pubitemid 47622532)
6. Gefen O, Balaban NQ. The importance of being persistent: heterogeneity of bacterial populations under antibiotic stress. FEMS Microbiol Rev 2009; 33: 704-717.
7. Allison KR, Brynildsen MP, Collins JJ. Heterogeneous bacterial persisters and engineering approaches to eliminate them. Curr OpinMicrobiol 2011; 14: 593-598.
8. Zhang Y, Yew WW, Barer MR. Targeting persisters for tuberculosis control. Antimicrob Agents Chemother 2012; 56: 2223-2230.
9. Ma C, Sim S, Shi W, Du L, Xing D, Zhang Y. Energy production genes sucB and ubiF are involved in persister survival and tolerance to multiple antibiotics and stresses in Escherichia coli. FEMS Microbiol Lett 2010; 303: 33-40.
10. Joers A, Kaldalu N, Tenson T. The frequency of persisters in Escherichia coli reflects the kinetics of awakening from dormancy. J Bacteriol 2010; 192: 3379-3384.
11. Hu Y, Coates AR. Transposon mutagenesis identifies genes which control antimicrobial drug tolerance in stationary-phase Escherichia coli. FEMS Microbiol Lett 2005; 243: 117-124. (Pubitemid 40164397)
12. Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K. Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett 2004; 230: 13-18. (Pubitemid 38091733)
13. Lewis K. Persister cells. Annu Rev Microbiol 2010; 64: 357-372.
14. Xu HS, Roberts N, Singleton FL, Attwell RW, Grimes DJ, Colwell RR. Survival and viability of nonculturable Escherichia coli and Vibrio cholerae in the estuarine and marine environment. Microbial Ecology 1982; 8: 313-323. (Pubitemid 13105941)
15. Hobby GL, Auerbach O, Lenert TF, Small MJ, Comer JV. The late emergence of M. tuberculosis in liquid cultures of pulmonary lesions resected from humans. Am Rev Tuberc 1954; 70: 191-218.
16. Zhang Y, Yang Y, Woods A, Cotter RJ, Sun Z. Resuscitation of dormant Mycobacterium tuberculosis by phospholipids or specific peptides. Biochem Biophys Res Commun 2001; 284: 542-547. (Pubitemid 32918012)
17. Greenwood D. Phenotypic resistance to antimicrobial agents. J Antimicrob Chemother 1985; 15: 653-655. (Pubitemid 15064682)
18. Zhang Y. Persistent and dormant tubercle bacilli and latent tuberculosis. Front Biosci 2004; 9: 1136-1156. (Pubitemid 39060834)
19. Zhou J, Zhang Y. Cancer stem cells: models, mechanisms and implications for improved treatment. Cell Cycle 2008; 7: 1360-1370. (Pubitemid 351872574)
20. Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S. Bacterial persistence as a phenotypic switch. Science 2004; 305: 1622-1625. (Pubitemid 39296357)
21. Stewart B, Rozen DE. Genetic variation for antibiotic persistence in Escherichia coli. Evolution 2012; 66: 933-939.
22. Glover WA, Yang Y, Zhang Y. Insights into the molecular basis of L-form formation and survival in Escherichia coli. PLoS ONE 2009; 4: e7316.
23. Domingue GJ. Demystifying pleomorphic forms in persistence and expression of disease: are they bacteria, and is peptidoglycan the solution? Discov Med 2010; 10: 234-246.
24. Kim JS, Heo P, Yang TJ, et al. Bacterial persisters tolerate antibiotics by not producing hydroxyl radicals. Biochem Biophys Res Commun 2011; 413: 105-110.
25. Bink A, Vandenbosch D, Coenye T, Nelis H, Cammue BP, Thevissen K. Superoxide dismutases are involved in Candida albicans biofilm persistence against miconazole. Antimicrob Agents Chemother 2011; 55: 4033-4037.
26. Gerdes K, Maisonneuve E. Bacterial persistence and toxin-antitoxin loci. Annu Rev Microbiol 2012; 66: 103-123.
27. Li J, Ji L, Shi W, Xie J, Zhang Y. Trans-translation mediates tolerance to multiple antibiotics and stresses in Escherichia coli. J Antimicrob Chemother 2013; 68: 2477-2481.
28. Sarathy J, Dartois V, Dick T, Gengenbacher M. Reduced drug uptake in phenotypically resistant nutrient-starved nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother 2013; 57: 1648-1653.
29. Fung DK, Chan EW, Chin ML, Chan RC. Delineation of a bacterial starvation stress response network which can mediate antibiotic tolerance development. Antimicrob Agents Chemother 2010; 54: 1082-1093.
30. Amato SM, Orman MA, Brynildsen MP. Metabolic control of persister formation in Escherichia coli. Mol Cell 2013; 50: 475-487.
31. Korch SB, Henderson TA, Hill TM. Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis. Mol Microbiol 2003; 50: 1199-1213. (Pubitemid 37475853)
32. Leung V, Levesque CM. A stress-inducible quorum-sensing peptide mediates the formation of persister cells with noninherited multidrug tolerance. J Bacteriol 2012; 194: 2265-2274.
33. Wu Y, Vulic M, Keren I, Lewis K. Role of oxidative stress in persister tolerance. Antimicrob Agents Chemother 2012; 56: 4922-4926.
34. Nguyen D, Joshi-Datar A, Lepine F et al. Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science 2011; 334: 982-986.
35. Shatalin K, Shatalina E, Mironov A, Nudler E. H2S: a universal defense against antibiotics in bacteria. Science 2011; 334: 986-990.
36. Gusarov I, Shatalin K, Starodubtseva M, Nudler E. Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics. Science 2009; 325: 1380-1384.
37. Dorr T, Vulic M, LewisK. Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLoS Biol 2010; 8: e1000317.
38. Kwan BW, Valenta JA, Benedik MJ, Wood TK. Arrested protein synthesis increases persister-like cell formation. Antimicrob Agents Chemother 2013; 57: 1468-1473
39. Hansen S, Lewis K, Vulic M. Role of global regulators and nucleotide metabolism in antibiotic tolerance in Escherichia coli. Antimicrob Agents Chemother 2008; 52: 2718-2726.
40. Hong SH, Wang X, OConnor HF, Benedik MJ, Wood TK. Bacterial persistence increases as environmental fitness decreases. Microb Biotechnol 2012; 5: 509-522.
41. Luidalepp H, Joers A, Kaldalu N, Tenson T. Age of inoculum strongly influences persister frequency and can mask effects of mutations implicated in altered persistence. J Bacteriol 2011; 193: 3598-3605.
42. Levin-Reisman I, Gefen O, Fridman O et al. Automated imaging with ScanLag reveals previously undetectable bacterial growth phenotypes. Nat Methods 2010; 7: 737-739.
43. Scherrer R, Moyed HS. Conditional impairment of cell division and altered lethality in hipA mutants of Escherichia coli K-12. J Bacteriol 1988; 170: 3321-3326.
44. Pearl S, Gabay C, Kishony R, Oppenheim A, Balaban NQ. Nongenetic individuality in the host-phage interaction. PLoS Biol 2008; 6: e120.
45. Wakamoto Y, Dhar N, Chait R, et al. Dynamic persistence of antibiotic-stressed mycobacteria. Science 2013; 339: 91-95.
46. Zhang Y, Heym B, Allen B, Young D, Cole S. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 1992; 358: 591-593.
47. Stricker RB, Johnson L. The pain of chronic Lyme disease: moving the discourse backward? FASEB J 2011; 25: 4085-4087.
48. McDermott W. Microbial persistence. Yale J Biol Med 1958; 30: 257-291.
49. Fauvart M, de Groote VN, Michiels J. Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. J Med Microbiol 2011; 60: 699-709.
50. McDermott W. Microbial persistence. Harvey Lecture 1969; 63: 1-31.
51. Barry CE 3rd, Boshoff HI, Dartois V et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 2009; 7: 845-855.
52. Mulcahy LR, Burns JL, Lory S, Lewis K. Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J Bacteriol 2010; 192: 6191-6199.
53. Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ. Ineffectiveness of tigecycline against persistent Borrelia burgdorferi. Antimicrob Agents Chemother 2010; 54: 643-651.
54. Embers ME, Barthold SW, Borda JT et al. Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection. PLoS ONE 2012; 7: e29914.
55. Finzi D, Blankson J, Siliciano JD et al. Latent infection of CD41 T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 1999; 5: 512-517. (Pubitemid 29220209)
56. Zoulim F. New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA. J Hepatol 2005; 42: 302-308. (Pubitemid 40254242)
57. Masaki T, Qu J, Cholewa-Waclaw J, BurrK, Raaum R, Rambukkana A. Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection. Cell 2013; 152: 51-67.
58. Das B, Kashino SS, Pulu I et al. CD2711 bone marrow mesenchymal stem cells may provide a niche for dormant Mycobacterium tuberculosis. Sci Transl Med 2013; 5: 170ra13.
59. Veening JW, Smits WK, Kuipers OP. Bistability, epigenetics, and bet-hedging in bacteria. Annu Rev Microbiol 2008; 62: 193-210.
60. Rotem E, Loinger A, Ronin I et al. Regulation of phenotypic variability by a thresholdbased mechanism underlies bacterial persistence. Proc Natl Acad Sci USA 2010; 107: 12541-12546.
61. Klapper I, Gilbert P, Ayati BP, Dockery J, Stewart PS. Senescence can explain microbial persistence. Microbiology 2007; 153: 3623-3630. (Pubitemid 350168240)
62. Girgis HS, Harris K, Tavazoie S. Large mutational target size for rapid emergence of bacterial persistence. Proc Natl Acad Sci USA 2012; 109: 12740-12745.
63. Spoering AL, Vulic M, Lewis K. GlpD and PlsB participate in persister cell formation in Escherichia coli. J Bacteriol 2006; 188: 5136-5144. (Pubitemid 44051479)
64. Shah D, Zhang Z, Khodursky A, Kaldalu N, Kurg K, Lewis K. Persisters: a distinct physiological state of E. coli. BMC Microbiol 2006; 6: 53.
65. Betts J, Lukey P, Robb L, McAdam R, Duncan K. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 2002; 43: 717-731. (Pubitemid 34597265)
66. Buckles EL, Wang X, Lockatell CV, Johnson DE, Donnenberg MS. PhoU enhances the ability of extraintestinal pathogenic Escherichia coli strain CFT073 to colonize the murine urinary tract. Microbiology 2006; 152: 153-160. (Pubitemid 43092403)
67. Shi W, Zhang Y. PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. J Antimicrob Chemother 2010; 65: 1237-1242.
68. Dahl JL, Kraus CN, Boshoff HI et al. The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc Natl Acad Sci USA 2003; 100: 10026-10031. (Pubitemid 37087062)
69. Norton JP, Mulvey MA. Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli. PLoS Pathog 2012; 8: e1002954.
70. Clarke MF, Dick JE, Dirks PB et al. Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006; 66: 9339-9344. (Pubitemid 44623625)
71. Holzman D. Genetic switch plays key role, converting ordinary topersister bacteria. Washington, DC: Microbe Magazine, 2007. Available at http://forms.asm.org/ microbe/index.asp?bid551533 (accessed 24 March 2013).
72. Allan EJ, Hoischen C, Gumpert J. Bacterial L-forms. Adv Appl Microbiol 2009; 68: 1-39.
73. Zhou J, Wulfkuhle J, Zhang H et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci USA 2007; 104: 16158-16163. (Pubitemid 350099378)
74. Pietras A. Cancer stem cells in tumor heterogeneity. Adv Cancer Res 2011; 112: 255-281.
75. Glickman MS, Sawyers CL. Converting cancer therapies into cures: lessons from infectious diseases. Cell 2012; 148: 1089-1098.
76. Dawson CC, Intapa C, Jabra-Rizk MA. Persisters: survival at the cellular level. PLoS Pathog 2011; 7: e1002121.
77. Ben-Jacob E, Coffey DS, Levine H. Bacterial survival strategies suggest rethinking cancer cooperativity. Trends Microbiol 2012; 20: 403-410.
78. Zhang Y, Mitchison D. The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis 2003; 7: 6-21. (Pubitemid 36427026)
79. Zhang Y, Permar S, Sun Z. Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide. J Med Microbiol 2002; 51: 42-49. (Pubitemid 34060132)
80. Zhang Y, Wade MM, Scorpio A, Zhang H, Sun Z. Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid. J Antimicrob Chemother 2003; 52: 790-795. (Pubitemid 37407806)
81. Shi W, Zhang X, Jiang X et al. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science 2011; 333: 1630-1632.
82. Zhang S, Chen J, Shi W, Liu W, Zhang WH, Zhang Y. Mutations in panD encoding aspartate decarboxylase are associated with pyrazinamide resistance in Mycobacterium tuberculosis.Emerg Microbes Infect 2013; 2: e34.
83. Deye GA, Gettayacamin M, Hansukjariya P, et al. Use of a rhesus Plasmodium cynomolgi model to screen for anti-hypnozoite activity of pharmaceutical substances. Am J Trop Med Hyg 2012; 86: 931-935.
84. Wade MM, Zhang Y. Effects of weak acids, UV and proton motive force inhibitors on pyrazinamide activity against Mycobacterium tuberculosis in vitro. J Antimicrob Chemother 2006; 58: 936-941.
85. Coates AR, Hu Y. Targeting non-multiplying organisms as a way to develop novel antimicrobials. Trends Pharmacol Sci 2008; 29: 143-150.
86. Nathan C. Fresh approaches to anti-infective therapies. Sci Transl Med 2012; 4: 140sr2.
87. Zhang Y. The magic bullets and tuberculosis drug targets. Annu Rev Pharmacol Toxicol 2005; 45: 529-564. (Pubitemid 40261816)
88. Mukamolova GV, Turapov OA, Young DI, Kaprelyants AS, Kell DB, Young M. A family of autocrine growth factors in Mycobacterium tuberculosis. Mol Microbiol 2002; 46: 623-635. (Pubitemid 35365599)
89. Orman MA, Brynildsen MP. Establishment of a method to rapidly assay bacterial persister metabolism. Antimicrob Agents Chemother 2013; 57: 4398-4409.
90. Somoskovi A, Wade MM, Sun Z, Zhang Y. Iron enhances the antituberculous activity of pyrazinamide. J Antimicrob Chemother 2004; 53: 192-196. (Pubitemid 38239949)
91. Byrne ST, Denkin SM, Zhang Y. Aspirin and ibuprofen enhance pyrazinamide treatment of murine tuberculosis. J Antimicrob Chemother 2007; 59: 313-316. (Pubitemid 47072074)
92. Allison KR, Brynildsen MP, Collins JJ. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature 2011; 473:216-220.
93. Grant SS, Kaufmann BB, Chand NS, Haseley N, Hung DT. Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals. Proc Natl Acad Sci USA 2012; 109: 12147-12152.
94. Morones-Ramirez JR, Winkler JA, Spina CS, Collins JJ. Silver enhances antibiotic activity against gram-negative bacteria. Sci Transl Med 2013; 5: 190ra81.
95. Kim JS, Heo P, Yang TJ, et al. Selective killing of bacterial persisters by a single chemical compound without affecting normal antibiotic-sensitive cells. Antimicrob Agents Chemother 2011; 55: 5380-5383.
96. Pan J, Bahar AA, Syed H, Ren D. Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by (Z)-4-bromo-5-(bromomethylene)-3- methylfuran- 2(5H)-one. PLoS ONE 2012; 7: e45778.
97. Aagaard C, Hoang T, Dietrich J, et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med 2011; 17: 189-194.
98. Wang CC, Zhu B, Fan X, Gicquel B, Zhang Y. Systems approach to tuberculosis vaccine development. Respirology 2013; 18: 412-420.
99. Lowrie DB, Tascon RE, Bonato VL et al. Therapy of tuberculosis in mice by DNA vaccination. Nature 1999; 400: 269-271. (Pubitemid 29334142)
100. van Opijnen T, Bodi KL, Camilli A. Tn-seq: high-throughput parallel sequencing for fitness and genetic interaction studies in microorganisms. Nat Methods 2009; 6: 767-772.
101. LaFleur MD, Kumamoto CA, Lewis K. Candida albicans biofilms produce antifungaltolerant persister cells. Antimicrob Agents Chemother 2006; 50: 3839-3846. (Pubitemid 44684901)
102. Cheng Q, Kyle DE, Gatton ML. Artemisinin resistance in Plasmodium falciparum: A process linked to dormancy? Int J Parasitol Drugs Drug Resist 2012; 2: 249-255.
103. Gupta PB, Chaffer CL, Weinberg RA. Cancer stem cells: mirage or reality? Nat Med 2009; 15: 1010-1012.
104. Gupta PB, Onder TT, Jiang G et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009; 138: 645-659.
105. Zhou JB, Zhang Y. Preclinical development of cancer stem cell drugs. Expert Opin Drug Discov 2009; 4: 741-752.
106. McCuneRMJr, McDermottW, Tompsett R. The fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. II. The conversion of tuberculous infection to the latent state by the administration of pyrazinamide and a companion drug. J Exp Med 1956; 104: 763-802.
107. Andries K, Verhasselt P, Guillemont J et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005; 307: 223-227. (Pubitemid 40116230)
108. Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. Int J Tuberc Lung Dis 1999; 3: S231-S279.
109. The World Health Organization. Treatment of tuberculosis: guidelines. 4th ed. Geneva: WHO, 2010.
110. Ryan FJ. Bacterial mutation in a stationary phase and the question of cell turnover. J Gen Microbiol 1959; 21: 530-549.
111. Zhou J, Zhang H, Gu P, Bai J, Margolick JB, Zhang Y. NF-kappaB pathway inhibitors preferentially inhibit breast cancer stem-like cells. Breast Cancer Res Treat 2008; 111: 419-427.
112. Zhou J, Zhang H, Gu P, Margolick JB, Yin D, Zhang Y. Cancer stem/progenitor cell active compound 8-quinolinol in combination with paclitaxel achieves an improved cure of breast cancer in the mouse model. Breast Cancer Res Treat 2009; 115: 269-277.
113. Yuan S, Wang F, ChenGet al. Effective elimination of cancer stem cells by a novel drug combination strategy. Stem Cells 2013; 31: 23-34.
114. Tashiro Y, Kawata K, Taniuchi A, Kakinuma K, May T, Okabe S. RelE-mediated dormancy is enhanced at high cell density in Escherichia coli. J Bacteriol 2012; 194: 1169-1176.
115. Kim Y, Wood TK. Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli. Biochem Biophys Res Commun 2009; 391: 209-213.
116. Deb C, Lee CM, Dubey VS et al. A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen. PLoS ONE 2009; 4: e6077.
117. Sureka K, Ghosh B, Dasgupta A, Basu J, Kundu M, Bose I. Positive feedback and noise activate the stringent response regulator rel in mycobacteria. PLoS ONE 2008; 3: e1771.
118. Debbia EA, Roveta S, Schito AM, Gualco L, Marchese A. Antibiotic persistence: the role of spontaneous DNA repair response. Microb Drug Resist 2001; 7: 335-342. (Pubitemid 34106307)
119. Dorr T, Lewis K, Vulic M. SOS response induces persistence to fluoroquinolones in Escherichia coli. PLoS Genet 2009; 5: e1000760.
120. Almiron M, Link AJ, Furlong D, Kolter R. A novel DNA-binding protein with regulatory and protective roles in starved Escherichia coli. Genes Dev 1992; 6: 2646-2654. (Pubitemid 23052891)
121. Pandey AK, Sassetti CM. Mycobacterial persistence requires the utilization of host cholesterol. Proc Natl Acad Sci USA 2008; 105: 4376-4380. (Pubitemid 351754388)
122. Adams KN, Takaki K, Connolly LE et al. Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell 2011; 145: 39-53.
123. Wang C, Mao Y, Yu J et al. PhoY2 of mycobacteria is required for metabolic homeostasis and stress response. J Bacteriol 2013; 195: 243-252.
124. Moker N, Dean CR, Tao J. Pseudomonas aeruginosa increases formation of multidrugtolerant persister cells in response to quorum-sensing signaling molecules. J Bacteriol 2010; 192: 1946-1955.
125. Vega NM, Allison KR, Khalil AS, Collins JJ. Signaling-mediated bacterial persister formation. Nat Chem Biol 2012; 8: 431-433.