8. Dhar N, McKinney JD, Manina G (2016) Phenotypic heterogeneity in Mycobacterium tuberculosis. Microbiol Spectrum 4(6):TBTB20021-2016
9. Desai SK, Kenney LJ (2019) Switching lifestyles is an in vivo adaptive strategy of bacterial
pathogens. Front Cell Infect Microbiol 9:421.
https://doi.org/10.3389/fcimb.2019.00421
10. Schro ¨ter L, Dersch P (2019) Phenotypic diversification of microbial pathogens–cooperating
and preparing for the future. J Mol Biol
431:4645–4655
11. Defraine V, Fauvart M, Michiels J (2018)
Fighting bacterial persistence: current and
emerging anti-persister strategies and therapeutics. Drug Resist Update 38:12–26
12. Meylan S, Andrews IW, Collins JJ (2018) Targeting antibiotic tolerance pathogen by pathogen. Cell 172:1228–1238
13. Richardson K, Bennion OT, Tan S et al (2016)
Temporal and intrinsic factors of rifampicin
tolerance in mycobacteria. Proc Natl Acad Sci
U S A 113:8302–8307
14. Brehm-Stecher BF, Johnson EA (2004) Singlecell microbiology: tools, technologies, and
applications. Microbiol Mol Biol Rev
68:538–559
15. Sliusarenko O, Heinritz J, Emonet T et al
(2011) High-throughput, subpixel precision
analysis of bacterial morphogenesis and intracellular spatio-temporal dynamics. Mol Microbiol 80:612–627
16. Young JW, Locke JC, Altinok A et al (2012)
Measuring single-cell gene expression dynamics in bacteria using fluorescence time-lapse
microscopy. Nat Protoc 7:80–88
17. Konry T, Sarkar S, Sabhachandani P et al
(2016) Innovative tools and technology for
analysis of single cells and cell-cell interaction.
Annu Rev Biomed Eng 18:259–284
18. Binder D, Drepper T, Jaeger K-E et al (2017)
Homogenizing bacterial cell factories: analysis
and engineering of phenotypic heterogeneity.
Metab Eng 42:145–156
19. Potvin-Trottier L, Luro S, Paulsson J (2018)
Microfluidics and single-cell microscopy to
study stochastic processes in bacteria. Curr
Opin Microbiol 43:186–192
20. Joyce G, Robertson BD, Williams KJ (2011) A
modified agar pad method for mycobacterial
live-cell imaging. BMC Res Notes 4:73
21. Golchin SA, Stratford J, Curry RJ et al (2012)
A microfluidic system for long-term time-lapse
microscopy studies of mycobacteria. Tuberculosis (Edinb) 92:489–496
22. Wakamoto Y, Dhar N, Chait R et al (2013)
Dynamic persistence of antibiotic-stressed
mycobacteria. Science 339:91–95
23. Martı ´nez-Hoyos M, Perez-Herran E, Gulten G
et al (2016) Antitubercular drugs for an old
target: GSK693 as a promising InhA direct
inhibitor. EBioMedicine 8:291–301
24. Sakatos A, Babunovic GH, Chase MR et al
(2018) Posttranslational modification of a
histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria. Sci Adv 4:
eaao1478
25. Manina G, Griego A, Singh LK et al (2019)
Preexisting variation in DNA damage response
predicts the fate of single mycobacteria under
stress. EMBO J 38:e101876
26. Manina G, Dhar N, McKinney JD (2015)
Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity
and induce nongrowing metabolically active
forms. Cell Host Microbe 17:32–46
27. Barisch C, Lo ´ pez-Jime ´nez AT, Soldati T
(2015) Live imaging of Mycobacterium marinum infection in Dictyostelium discoideum.
Methods Mol Biol 1285:369–385
28. Delince ´ MJ, Bureau JB, Lo ´pez-Jime ´nez AT
et al (2016) A microfluidic cell-trapping device
for single-cell tracking of host-microbe interactions. Lab Chip 16:3276–3285
29. Lerner TR, Borel S, Greenwood DJ et al
(2017) Mycobacterium tuberculosis replicates
within necrotic human macrophages. J Cell
Biol 216:583–594
30. Santi I, McKinney JD (2015) Chromosome
organization and replisome dynamics in Mycobacterium smegmatis. MBio 6:e01999–e01914
31. Trojanowski D, Hoło ´wka J, Ginda K et al
(2017) Multifork chromosome replication in
slow-growing bacteria. Sci Rep 7:43836
32. Logsdon MM, Ho PY, Papavinasasundaram K
et al (2017) A parallel adder coordinates mycobacterial cell-cycle progression and cell-size
homeostasis in the context of asymmetric
growth and organization. Curr Biol
27:3367–3374
33. Mann KM, Huang DL, Hooppaw AJ et al
(2017) Rv0004 is a new essential member of
the mycobacterial DNA replication machinery.
PLoS Genet 13:e1007115
34. Pen ˜a-Zalbidea S, Huang AY, Kavunja HW et al
(2018) Chemoenzymatic radiosynthesis of
2-deoxy-2-[18F]fluoro-d-trehalose ([18F]-2FDTre): a PET radioprobe for in vivo tracing
of trehalose metabolism. Carbohydr Res
472:16–22
35. Cheng Y, Xie J, Lee KH et al (2018) Rapid and
specific labeling of single live Mycobacterium
tuberculosis with a dual-targeting fluorogenic
probe. Sci Transl Med 10:eaar4470
36. Hodges HL, Brown RA, Crooks JA et al
(2018) Imaging mycobacterial growth and
228
Giulia Manina and Neeraj Dhar
9. Desai SK, Kenney LJ (2019) Switching lifestyles is an in vivo adaptive strategy of bacterial
pathogens. Front Cell Infect Microbiol 9:421.
https://doi.org/10.3389/fcimb.2019.00421
10. Schro ¨ter L, Dersch P (2019) Phenotypic diversification of microbial pathogens–cooperating
and preparing for the future. J Mol Biol
431:4645–4655
11. Defraine V, Fauvart M, Michiels J (2018)
Fighting bacterial persistence: current and
emerging anti-persister strategies and therapeutics. Drug Resist Update 38:12–26
12. Meylan S, Andrews IW, Collins JJ (2018) Targeting antibiotic tolerance pathogen by pathogen. Cell 172:1228–1238
13. Richardson K, Bennion OT, Tan S et al (2016)
Temporal and intrinsic factors of rifampicin
tolerance in mycobacteria. Proc Natl Acad Sci
U S A 113:8302–8307
14. Brehm-Stecher BF, Johnson EA (2004) Singlecell microbiology: tools, technologies, and
applications. Microbiol Mol Biol Rev
68:538–559
15. Sliusarenko O, Heinritz J, Emonet T et al
(2011) High-throughput, subpixel precision
analysis of bacterial morphogenesis and intracellular spatio-temporal dynamics. Mol Microbiol 80:612–627
16. Young JW, Locke JC, Altinok A et al (2012)
Measuring single-cell gene expression dynamics in bacteria using fluorescence time-lapse
microscopy. Nat Protoc 7:80–88
17. Konry T, Sarkar S, Sabhachandani P et al
(2016) Innovative tools and technology for
analysis of single cells and cell-cell interaction.
Annu Rev Biomed Eng 18:259–284
18. Binder D, Drepper T, Jaeger K-E et al (2017)
Homogenizing bacterial cell factories: analysis
and engineering of phenotypic heterogeneity.
Metab Eng 42:145–156
19. Potvin-Trottier L, Luro S, Paulsson J (2018)
Microfluidics and single-cell microscopy to
study stochastic processes in bacteria. Curr
Opin Microbiol 43:186–192
20. Joyce G, Robertson BD, Williams KJ (2011) A
modified agar pad method for mycobacterial
live-cell imaging. BMC Res Notes 4:73
21. Golchin SA, Stratford J, Curry RJ et al (2012)
A microfluidic system for long-term time-lapse
microscopy studies of mycobacteria. Tuberculosis (Edinb) 92:489–496
22. Wakamoto Y, Dhar N, Chait R et al (2013)
Dynamic persistence of antibiotic-stressed
mycobacteria. Science 339:91–95
23. Martı ´nez-Hoyos M, Perez-Herran E, Gulten G
et al (2016) Antitubercular drugs for an old
target: GSK693 as a promising InhA direct
inhibitor. EBioMedicine 8:291–301
24. Sakatos A, Babunovic GH, Chase MR et al
(2018) Posttranslational modification of a
histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria. Sci Adv 4:
eaao1478
25. Manina G, Griego A, Singh LK et al (2019)
Preexisting variation in DNA damage response
predicts the fate of single mycobacteria under
stress. EMBO J 38:e101876
26. Manina G, Dhar N, McKinney JD (2015)
Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity
and induce nongrowing metabolically active
forms. Cell Host Microbe 17:32–46
27. Barisch C, Lo ´ pez-Jime ´nez AT, Soldati T
(2015) Live imaging of Mycobacterium marinum infection in Dictyostelium discoideum.
Methods Mol Biol 1285:369–385
28. Delince ´ MJ, Bureau JB, Lo ´pez-Jime ´nez AT
et al (2016) A microfluidic cell-trapping device
for single-cell tracking of host-microbe interactions. Lab Chip 16:3276–3285
29. Lerner TR, Borel S, Greenwood DJ et al
(2017) Mycobacterium tuberculosis replicates
within necrotic human macrophages. J Cell
Biol 216:583–594
30. Santi I, McKinney JD (2015) Chromosome
organization and replisome dynamics in Mycobacterium smegmatis. MBio 6:e01999–e01914
31. Trojanowski D, Hoło ´wka J, Ginda K et al
(2017) Multifork chromosome replication in
slow-growing bacteria. Sci Rep 7:43836
32. Logsdon MM, Ho PY, Papavinasasundaram K
et al (2017) A parallel adder coordinates mycobacterial cell-cycle progression and cell-size
homeostasis in the context of asymmetric
growth and organization. Curr Biol
27:3367–3374
33. Mann KM, Huang DL, Hooppaw AJ et al
(2017) Rv0004 is a new essential member of
the mycobacterial DNA replication machinery.
PLoS Genet 13:e1007115
34. Pen ˜a-Zalbidea S, Huang AY, Kavunja HW et al
(2018) Chemoenzymatic radiosynthesis of
2-deoxy-2-[18F]fluoro-d-trehalose ([18F]-2FDTre): a PET radioprobe for in vivo tracing
of trehalose metabolism. Carbohydr Res
472:16–22
35. Cheng Y, Xie J, Lee KH et al (2018) Rapid and
specific labeling of single live Mycobacterium
tuberculosis with a dual-targeting fluorogenic
probe. Sci Transl Med 10:eaar4470
36. Hodges HL, Brown RA, Crooks JA et al
(2018) Imaging mycobacterial growth and
228
Giulia Manina and Neeraj Dhar