tuberculosis. Tuberculosis (Edinb) 88(Suppl
1):S25–S33.
https://doi.org/10.1016/
S1472-9792(08)70034-9
9. Lopez Quezada L, Silve S, Kelinske M, Liba A,
Diaz Gonzalez C, Kotev M, Goullieux L,
Sans S, Roubert C, Lagrange S, Bacque E,
Couturier C, Pellet A, Blanc I, Ferron M,
Debu F, Li K, Aube J, Roberts J, Little D,
Ling Y, Zhang J, Gold B, Nathan C (2019)
Bactericidal disruption of magnesium metallostasis in Mycobacterium tuberculosis is counteracted by mutations in the metal ion transporter
CorA. MBio 10(4). https://doi.org/10.
1128/mBio.01405-19
10. Lopez Quezada L, Li K, McDonald SL,
Nguyen Q, Perkowski AJ, Pharr CW, Gold B,
Roberts J, McAulay K, Saito K, Somersan
Karakaya S, Javidnia PE, Porras de
Francisco E, Amieva MM, Di Az SP, Mendoza
Losana A, Zimmerman M, Liang HH,
Zhang J, Dartois V, Sans S, Lagrange S,
Goullieux L, Roubert C, Nathan C, Aube J
(2019) Dual-pharmacophore pyrithione-containing cephalosporins kill both replicating
and nonreplicating Mycobacterium tuberculosis.
ACS Infect Dis 5(8):1433–1445. https://doi.
org/10.1021/acsinfecdis.9b00112
11. Grant SS, Kawate T, Nag PP, Silvis MR,
Gordon K, Stanley SA, Kazyanskaya E,
Nietupski R, Golas A, Fitzgerald M, Cho S,
Franzblau SG, Hung DT (2013) Identification
of novel inhibitors of nonreplicating Mycobacterium tuberculosis using a carbon starvation
model. ACS Chem Biol 8(10):2224–2234.
https://doi.org/10.1021/cb4004817
12. Mak PA, Rao SP, Ping Tan M, Lin X, Chyba J,
Tay J, Ng SH, Tan BH, Cherian J,
Duraiswamy J, Bifani P, Lim V, Lee BH, Ling
Ma N, Beer D, Thayalan P, Kuhen K,
Chatterjee A, Supek F, Glynne R, Zheng J,
Boshoff HI, Barry CE 3rd, Dick T, Pethe K,
Camacho LR (2012) A high-throughput
screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis. ACS Chem Biol 7(7):1190–1197. https://
doi.org/10.1021/cb2004884
13. Loebel RO, Shorr E, Richardson HB (1933)
The influence of foodstuffs upon the respiratory metabolism and growth of human tubercle bacilli. J Bacteriol 26(2):139–166
14. Loebel RO, Shorr E, Richardson HB (1933)
The influence of adverse conditions upon the
respiratory metabolism and growth of human
tubercle bacilli. J Bacteriol 26(2):167–200
15. Nyka W (1974) Studies on the effect of starvation on mycobacteria. Infect Immun 9
(5):843–850
16. Betts JC, Lukey PT, Robb LC, McAdam RA,
Duncan K (2002) Evaluation of a nutrient
starvation model of Mycobacterium tuberculosis
persistence by gene and protein expression
profiling. Mol Microbiol 43(3):717–731
17. Gengenbacher M, Rao SP, Pethe K, Dick T
(2010) Nutrient-starved, non-replicating
Mycobacterium tuberculosis requires respiration, ATP synthase and isocitrate lyase for
maintenance of ATP homeostasis and viability.
Microbiology 156(Pt 1):81–87. https://doi.
org/10.1099/mic.0.033084-0
18. Xie Z, Siddiqi N, Rubin EJ (2005) Differential
antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates. Antimicrob Agents
Chemother 49(11):4778–4780. https://doi.
org/10.1128/AAC.49.11.4778-4780.2005
19. Wayne LG (1994) Dormancy of Mycobacterium tuberculosis and latency of disease. Eur J
Clin Microbiol Infect Dis 13(11):908–914
20. Wayne LG, Hayes LG (1996) An in vitro
model for sequential study of shiftdown of
Mycobacterium tuberculosis through two stages
of nonreplicating persistence. Infect Immun 64
(6):2062–2069
21. Wayne LG, Sramek HA (1994) Metronidazole
is bactericidal to dormant cells of Mycobacterium tuberculosis. Antimicrob Agents Chemother 38(9):2054–2058
22. Hugonnet JE, Tremblay LW, Boshoff HI,
Barry CE 3rd, Blanchard JS (2009)
Meropenem-clavulanate is effective against
extensively
drug-resistant
Mycobacterium
tuberculosis. Science 323(5918):1215–1218.
https://doi.org/10.1126/science.1167498
23. Via LE, Lin PL, Ray SM, Carrillo J, Allen SS,
Eum SY, Taylor K, Klein E, Manjunatha U,
Gonzales J, Lee EG, Park SK, Raleigh JA,
Cho SN, McMurray DN, Flynn JL, Barry CE
3rd (2008) Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman
primates. Infect Immun 76(6):2333–2340.
https://doi.org/10.1128/IAI.01515-07
24. Brooks JV, Furney SK, Orme IM (1999) Metronidazole therapy in mice infected with tuberculosis. Antimicrob Agents Chemother 43
(5):1285–1288
25. Lin PL, Dartois V, Johnston PJ, Janssen C,
Via L, Goodwin MB, Klein E, Barry CE 3rd,
Flynn JL (2012) Metronidazole prevents reactivation of latent Mycobacterium tuberculosis
infection in macaques. Proc Natl Acad Sci U S
A 109(35):14188–14193. https://doi.org/
10.1073/pnas.1121497109
26. Hoff DR, Caraway ML, Brooks EJ, Driver ER,
Ryan GJ, Peloquin CA, Orme IM, Basaraba RJ,
Lenaerts AJ (2008) Metronidazole lacks antibacterial activity in guinea pigs infected with
Mycobacterium tuberculosis. Antimicrob Agents
Chemother 52(11):4137–4140. https://doi.
org/10.1128/AAC.00196-08
Multi-stress Model for Nonreplicating M. tuberculosis
633
1):S25–S33.
https://doi.org/10.1016/
S1472-9792(08)70034-9
9. Lopez Quezada L, Silve S, Kelinske M, Liba A,
Diaz Gonzalez C, Kotev M, Goullieux L,
Sans S, Roubert C, Lagrange S, Bacque E,
Couturier C, Pellet A, Blanc I, Ferron M,
Debu F, Li K, Aube J, Roberts J, Little D,
Ling Y, Zhang J, Gold B, Nathan C (2019)
Bactericidal disruption of magnesium metallostasis in Mycobacterium tuberculosis is counteracted by mutations in the metal ion transporter
CorA. MBio 10(4). https://doi.org/10.
1128/mBio.01405-19
10. Lopez Quezada L, Li K, McDonald SL,
Nguyen Q, Perkowski AJ, Pharr CW, Gold B,
Roberts J, McAulay K, Saito K, Somersan
Karakaya S, Javidnia PE, Porras de
Francisco E, Amieva MM, Di Az SP, Mendoza
Losana A, Zimmerman M, Liang HH,
Zhang J, Dartois V, Sans S, Lagrange S,
Goullieux L, Roubert C, Nathan C, Aube J
(2019) Dual-pharmacophore pyrithione-containing cephalosporins kill both replicating
and nonreplicating Mycobacterium tuberculosis.
ACS Infect Dis 5(8):1433–1445. https://doi.
org/10.1021/acsinfecdis.9b00112
11. Grant SS, Kawate T, Nag PP, Silvis MR,
Gordon K, Stanley SA, Kazyanskaya E,
Nietupski R, Golas A, Fitzgerald M, Cho S,
Franzblau SG, Hung DT (2013) Identification
of novel inhibitors of nonreplicating Mycobacterium tuberculosis using a carbon starvation
model. ACS Chem Biol 8(10):2224–2234.
https://doi.org/10.1021/cb4004817
12. Mak PA, Rao SP, Ping Tan M, Lin X, Chyba J,
Tay J, Ng SH, Tan BH, Cherian J,
Duraiswamy J, Bifani P, Lim V, Lee BH, Ling
Ma N, Beer D, Thayalan P, Kuhen K,
Chatterjee A, Supek F, Glynne R, Zheng J,
Boshoff HI, Barry CE 3rd, Dick T, Pethe K,
Camacho LR (2012) A high-throughput
screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis. ACS Chem Biol 7(7):1190–1197. https://
doi.org/10.1021/cb2004884
13. Loebel RO, Shorr E, Richardson HB (1933)
The influence of foodstuffs upon the respiratory metabolism and growth of human tubercle bacilli. J Bacteriol 26(2):139–166
14. Loebel RO, Shorr E, Richardson HB (1933)
The influence of adverse conditions upon the
respiratory metabolism and growth of human
tubercle bacilli. J Bacteriol 26(2):167–200
15. Nyka W (1974) Studies on the effect of starvation on mycobacteria. Infect Immun 9
(5):843–850
16. Betts JC, Lukey PT, Robb LC, McAdam RA,
Duncan K (2002) Evaluation of a nutrient
starvation model of Mycobacterium tuberculosis
persistence by gene and protein expression
profiling. Mol Microbiol 43(3):717–731
17. Gengenbacher M, Rao SP, Pethe K, Dick T
(2010) Nutrient-starved, non-replicating
Mycobacterium tuberculosis requires respiration, ATP synthase and isocitrate lyase for
maintenance of ATP homeostasis and viability.
Microbiology 156(Pt 1):81–87. https://doi.
org/10.1099/mic.0.033084-0
18. Xie Z, Siddiqi N, Rubin EJ (2005) Differential
antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates. Antimicrob Agents
Chemother 49(11):4778–4780. https://doi.
org/10.1128/AAC.49.11.4778-4780.2005
19. Wayne LG (1994) Dormancy of Mycobacterium tuberculosis and latency of disease. Eur J
Clin Microbiol Infect Dis 13(11):908–914
20. Wayne LG, Hayes LG (1996) An in vitro
model for sequential study of shiftdown of
Mycobacterium tuberculosis through two stages
of nonreplicating persistence. Infect Immun 64
(6):2062–2069
21. Wayne LG, Sramek HA (1994) Metronidazole
is bactericidal to dormant cells of Mycobacterium tuberculosis. Antimicrob Agents Chemother 38(9):2054–2058
22. Hugonnet JE, Tremblay LW, Boshoff HI,
Barry CE 3rd, Blanchard JS (2009)
Meropenem-clavulanate is effective against
extensively
drug-resistant
Mycobacterium
tuberculosis. Science 323(5918):1215–1218.
https://doi.org/10.1126/science.1167498
23. Via LE, Lin PL, Ray SM, Carrillo J, Allen SS,
Eum SY, Taylor K, Klein E, Manjunatha U,
Gonzales J, Lee EG, Park SK, Raleigh JA,
Cho SN, McMurray DN, Flynn JL, Barry CE
3rd (2008) Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman
primates. Infect Immun 76(6):2333–2340.
https://doi.org/10.1128/IAI.01515-07
24. Brooks JV, Furney SK, Orme IM (1999) Metronidazole therapy in mice infected with tuberculosis. Antimicrob Agents Chemother 43
(5):1285–1288
25. Lin PL, Dartois V, Johnston PJ, Janssen C,
Via L, Goodwin MB, Klein E, Barry CE 3rd,
Flynn JL (2012) Metronidazole prevents reactivation of latent Mycobacterium tuberculosis
infection in macaques. Proc Natl Acad Sci U S
A 109(35):14188–14193. https://doi.org/
10.1073/pnas.1121497109
26. Hoff DR, Caraway ML, Brooks EJ, Driver ER,
Ryan GJ, Peloquin CA, Orme IM, Basaraba RJ,
Lenaerts AJ (2008) Metronidazole lacks antibacterial activity in guinea pigs infected with
Mycobacterium tuberculosis. Antimicrob Agents
Chemother 52(11):4137–4140. https://doi.
org/10.1128/AAC.00196-08
Multi-stress Model for Nonreplicating M. tuberculosis
633