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Chapter 23 : Acid-Fast Positive and Acid-Fast Negative : The Koch Paradox

Authors: Catherine Vilchèze1, Laurent Kremer2
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Affiliations: 1: Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; 2: IRIM (ex-CPBS) UMR 9004, Infectious Disease Research Institute of Montpellier (IDRIM), Université de Montpellier, CNRS, 34293 Montpellier, France
Content Type: Monograph
Publication Year: 2017

Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis

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Abstract:

possesses a unique cell wall architecture that is distinct from both Gram-negative and Gram-positive bacteria. The cell wall consists of a thick, lipid-rich outer layer composed primarily of mycolic acids ( ) ( Fig. 1 ). This lipid layer lies on top of a layer of peptidoglycan and the polysaccharide arabinogalactan, which, in turn, are anchored to the inner lipid membrane common to all bacteria ( ). The overall thick waxy coat renders acid-fast (AF) mycobacteria resistant to Gram staining. When stained with alternative dyes, the cell wall is resistant to decolorization with acid alcohol, thus giving these bacteria their sobriquet “acid-fast.” This unique AF property has been the basis for the continuous development of staining procedures over the past century and remains the cornerstone for the diagnosis of tuberculosis (TB), especially in low-income and middle-income countries where more than 90% of TB cases occur ( ). The Ziehl-Neelsen (ZN) stain, also known as the AF stain, which is used in microscopic detection of , was originally developed independently by Ziehl and Neelsen, who improved on the early work of Koch, Rindfleisch, and Ehrlich (see below).

Citation: Vilchèze C, Kremer L. 2017. Acid-Fast Positive and Acid-Fast Negative : The Koch Paradox, p 519-532. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0003-2015
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Acid-Fast Positive and Acid-Fast Negative Mycobacterium tuberculosis: The Koch Paradox
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Citation: Vilchèze C, Kremer L. 2017. Acid-Fast Positive and Acid-Fast Negative : The Koch Paradox, p 519-532. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0003-2015
/content/10.1128/9781555819569.chap23.fig23-1
Figure 1

Chemical structures of the major mycolic acids of . Cyclopropane rings and methyl branches are shown and annotated with the -adenosyl methionine-dependent methyl transferases responsible for their synthesis. , ; , .

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Image of Figure 1
Figure 1

Chemical structures of the major mycolic acids of . Cyclopropane rings and methyl branches are shown and annotated with the -adenosyl methionine-dependent methyl transferases responsible for their synthesis. , ; , .

Citation: Vilchèze C, Kremer L. 2017. Acid-Fast Positive and Acid-Fast Negative : The Koch Paradox, p 519-532. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0003-2015
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Figure 2

Staining of using ZN (left) and auramine O (right). Magnification, ×100.

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10.1128/9781555819569/fig23-2.gif
Image of Figure 2
Figure 2

Staining of using ZN (left) and auramine O (right). Magnification, ×100.

Citation: Vilchèze C, Kremer L. 2017. Acid-Fast Positive and Acid-Fast Negative : The Koch Paradox, p 519-532. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0003-2015
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Figure 3

Ser/Thr kinase-dependent signaling cascade resulting in phosphorylation of KasB and loss of acid-fastness. Modification of the cell wall composition in response to exogenous cues is central for adaptation to different environmental conditions. In response to an external signal, mycobacterial Ser/Thr kinases phosphorylate the different FAS-II components, including the β-ketoacyl ACP synthase KasB involved in the addition of the last carbon atoms during the mycolic acid elongation step. Phosphorylation on Thr334 and Thr336 decreases the condensation activity of KasB, resulting in the production of shorter mycolic acids, which probably affects the packing of the lipid layer and also results in the loss of the AF property and severe attenuation in mice.

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10.1128/9781555819569/fig23-3.gif
Image of Figure 3
Figure 3

Ser/Thr kinase-dependent signaling cascade resulting in phosphorylation of KasB and loss of acid-fastness. Modification of the cell wall composition in response to exogenous cues is central for adaptation to different environmental conditions. In response to an external signal, mycobacterial Ser/Thr kinases phosphorylate the different FAS-II components, including the β-ketoacyl ACP synthase KasB involved in the addition of the last carbon atoms during the mycolic acid elongation step. Phosphorylation on Thr334 and Thr336 decreases the condensation activity of KasB, resulting in the production of shorter mycolic acids, which probably affects the packing of the lipid layer and also results in the loss of the AF property and severe attenuation in mice.

Citation: Vilchèze C, Kremer L. 2017. Acid-Fast Positive and Acid-Fast Negative : The Koch Paradox, p 519-532. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0003-2015
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Figure 4

Loss of AF staining coincides with the accumulation of TAG-containing intracellular lipid inclusions. Dual staining of grown under multiple stress conditions, using auramine O for AF-staining (green) and Nile red as a neutral lipid stain (red). Bacilli were observed by confocal laser scanning microscopy. Overlaid images of the dual-stained bacteria are shown. Bar = 4 μm. Quantification of the number of AF-positive and lipid-stain-positive bacilli grown as in (A). Auramine O-stained and Nile red-stained positive cells were counted from multiple scans. (Adapted from Deb et al. 4(6):e6077 with permission of the publisher.)

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Image of Figure 4
Figure 4

Loss of AF staining coincides with the accumulation of TAG-containing intracellular lipid inclusions. Dual staining of grown under multiple stress conditions, using auramine O for AF-staining (green) and Nile red as a neutral lipid stain (red). Bacilli were observed by confocal laser scanning microscopy. Overlaid images of the dual-stained bacteria are shown. Bar = 4 μm. Quantification of the number of AF-positive and lipid-stain-positive bacilli grown as in (A). Auramine O-stained and Nile red-stained positive cells were counted from multiple scans. (Adapted from Deb et al. 4(6):e6077 with permission of the publisher.)

Citation: Vilchèze C, Kremer L. 2017. Acid-Fast Positive and Acid-Fast Negative : The Koch Paradox, p 519-532. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0003-2015
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References

/content/book/10.1128/9781555819569.chap23
1. Pawełczyk J,, Kremer L . 2014. The molecular genetics of mycolic acid biosynthesis. Microbiol Spectr 2 : MGM2–0003–2013. [CrossRef] [PubMed]
2. Brennan PJ,, Nikaido H . 1995. The envelope of mycobacteria. Annu Rev Biochem 64 : 29– 63.[CrossRef] [PubMed]
3. Hoffmann C,, Leis A,, Niederweis M,, Plitzko JM,, Engelhardt H . 2008. Disclosure of the mycobacterial outer membrane: cryo-electron tomography and vitreous sections reveal the lipid bilayer structure. Proc Natl Acad Sci USA 105 : 3963– 3967.[CrossRef]
4. Zuber B,, Chami M,, Houssin C,, Dubochet J,, Griffiths G,, Daffé M . 2008. Direct visualization of the outer membrane of mycobacteria and corynebacteria in their native state. J Bacteriol 190 : 5672– 5680.[CrossRef] [PubMed]
5. Foulds J,, O’Brien R . 1998. New tools for the diagnosis of tuberculosis: the perspective of developing countries. Int J Tuberc Lung Dis 2 : 778– 783.[PubMed]
6. Walters SB,, Dubnau E,, Kolesnikova I,, Laval F,, Daffe M,, Smith I . 2006. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol Microbiol 60 : 312– 330.[CrossRef]
7. Barkan D,, Hedhli D,, Yan HG,, Huygen K,, Glickman MS . 2012. Mycobacterium tuberculosis lacking all mycolic acid cyclopropanation is viable but highly attenuated and hyperinflammatory in mice. Infect Immun 80 : 1958– 1968.[CrossRef]
8. Fukuda T,, Matsumura T,, Ato M,, Hamasaki M,, Nishiuchi Y,, Murakami Y,, Maeda Y,, Yoshimori T,, Matsumoto S,, Kobayashi K,, Kinoshita T,, Morita YS . 2013. Critical roles for lipomannan and lipoarabinomannan in cell wall integrity of mycobacteria and pathogenesis of tuberculosis. MBio 4 : e00472-e12.[CrossRef]
9. Rist N,, Grumbach F,, Cals S,, Riebel J . 1952. Isonicotinic acid hydrazide (INH); antituberculous activity in mice; creation of resistant strains in vitro. [In French.] Ann Inst Pasteur (Paris) 82 : 757– 760.[PubMed]
10. Takayama K,, Wang L,, David HL . 1972. Effect of isoniazid on the in vivo mycolic acid synthesis, cell growth, and viability of Mycobacterium tuberculosis . Antimicrob Agents Chemother 2 : 29– 35. [CrossRef] [PubMed]
11. Bhatt A,, Fujiwara N,, Bhatt K,, Gurcha SS,, Kremer L,, Chen B,, Chan J,, Porcelli SA,, Kobayashi K,, Besra GS,, Jacobs WR Jr . 2007. Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. Proc Natl Acad Sci USA 104 : 5157– 5162.[CrossRef]
12. Seiler P,, Ulrichs T,, Bandermann S,, Pradl L,, Jörg S,, Krenn V,, Morawietz L,, Kaufmann SHE,, Aichele P . 2003. Cell-wall alterations as an attribute of Mycobacterium tuberculosis in latent infection. J Infect Dis 188 : 1326– 1331.[CrossRef]
13. Koch R . 1882. Die Atiologie der Tuberkulose. Berl Klinischen Wochenschr 15 : 221– 230.
14. Bishop PJ,, Neumann G . 1970. The history of the Ziehl-Neelsen stain. Tubercle 51 : 196– 206.[CrossRef]
15. Ehrlich P . 1882. A method for staining the tubercle bacillus. Dtsch Med Wochenschr 8 : 269– 270.
16. Gabbett HS . 1887. Rapid staining of the tubercle bacillus. Lancet 129 : 757.
17. Kinyoun JJ . 1915. A note on Uhlenhuths method for sputum examination, for tubercle bacilli. Am J Public Health (NY) 5 : 867– 870. [CrossRef] [PubMed]
18. Hallberg V . 1946. Origin of the Nachtblau method for staining tubercle bacilli and its preliminary use. Acta Med Scand Suppl 180 : 6– 8.
19. Hallberg V . 1946. Experiences with regard to the tubercle micro-organism obtained by the new staining method. Acta Med Scand Suppl 180 : 22– 24.
20. Tison F . 1951. La coloration de Hallberg modifiée pour la mise en évidence du bacille tuberculeux. Ann Inst Pasteur (Paris) 80 : 207– 210.[PubMed]
21. Hok TT . 1962. A simple and rapid cold-staining method for acid-fast bacteria. Am Rev Respir Dis 85 : 753– 754.
22. Allen JL . 1992. A modified Ziehl-Neelsen stain for mycobacteria. Med Lab Sci 49 : 99– 102.[PubMed]
23. Hagemann PKH . 1938. Fluoreszenzfarbung von Tuberkelbakterien mit Auramin. Munch Med Wochenschr 85 : 1066– 1068.
24. Degommier J . 1957. Nouvelle technique de coloration des bacilles tuberculeux pour la recherche en fluorescence. Ann Inst Pasteur (Paris) 92 : 692– 694.
25. Truant JP,, Brett WA,, Thomas W Jr . 1962. Fluorescence microscopy of tubercle bacilli stained with auramine and rhodamine. Henry Ford Hosp Med Bull 10 : 287– 296.[PubMed]
26. Alausa KO,, Osoba AO,, Montefiore D,, Sogbetun OA . 1977. Laboratory diagnosis of tuberculosis in a developing country 1968–1975. Afr J Med Med Sci 6 : 103– 108.[PubMed]
27. Angra P,, Becx-Bleumink M,, Gilpin C,, Joloba M,, Jost K,, Kam KM,, Kim SJ,, Lumb R,, Mitarai S,, Ramsay A,, Ridderhof J,, Rieder HL,, Selvakumar N,, van Beers S,, van Cleeff M,, Van Deun A,, Vincent V . 2007. Ziehl-Neelsen staining: strong red on weak blue, or weak red under strong blue? Int J Tuberc Lung Dis 11 : 1160– 1161.[PubMed]
28. Levy H,, Feldman C,, Sacho H,, van der Meulen H,, Kallenbach J,, Koornhof H . 1989. A reevaluation of sputum microscopy and culture in the diagnosis of pulmonary tuberculosis. Chest 95 : 1193– 1197.[CrossRef] [PubMed]
29. Petersen KF,, Urbanczik R . 1982. Microscopic and cultural methods for the laboratory diagnosis of tuberculosis. A short historical review (author’s transl). (In German.) Zentralbl Bakteriol Mikrobiol Hyg [A] 251 : 308– 325.
30. Siddiqi K,, Lambert ML,, Walley J . 2003. Clinical diagnosis of smear-negative pulmonary tuberculosis in low-income countries: the current evidence. Lancet Infect Dis 3 : 288– 296.[CrossRef]
31. Aber VR,, Allen BW,, Mitchison DA,, Ayuma P,, Edwards EA,, Keyes AB . 1980. Laboratory studies on isolated positive cultures and the efficiency of direct smear examination. Tubercle 61 : 123– 133.[CrossRef]
32. Van Deun A,, Hamid Salim A,, Aung KJ,, Hossain MA,, Chambugonj N,, Hye MA,, Kawria A,, Declercq E . 2005. Performance of variations of carbolfuchsin staining of sputum smears for AFB under field conditions. Int J Tuberc Lung Dis 9 : 1127– 1133.[PubMed]
33. Tuberculosis Division International Union Against Tuberculosis and Lung Disease . 2005. Tuberculosis bacteriology--priorities and indications in high prevalence countries: position of the technical staff of the Tuberculosis Division of the International Union Against Tuberculosis and Lung Disease. Int J Tuberc Lung Dis 9 : 355– 361.[PubMed]
34. Chakravorty S,, Sen MK,, Tyagi JS . 2005. Diagnosis of extrapulmonary tuberculosis by smear, culture, and PCR using universal sample processing technology. J Clin Microbiol 43 : 4357– 4362. [CrossRef]
35. Karstaedt AS,, Jones N,, Khoosal M,, Crewe-Brown HH . 1998. The bacteriology of pulmonary tuberculosis in a population with high human immunodeficiency virus seroprevalence. Int J Tuberc Lung Dis 2 : 312– 316.[PubMed]
36. Khan EA,, Starke JR . 1995. Diagnosis of tuberculosis in children: increased need for better methods. Emerg Infect Dis 1 : 115– 123. [CrossRef] [PubMed]
37. Shapiro HM,, Hänscheid T . 2008. Fuchsin fluorescence in Mycobacterium tuberculosis: the Ziehl-Neelsen stain in a new light. J Microbiol Methods 74 : 119– 120.[CrossRef]
38. Gruft H . 1978. Evaluation of mycobacteriology laboratories: the acid-fast smear. Health Lab Sci 15 : 215– 220.[PubMed]
39. Somoskövi A,, Hotaling JE,, Fitzgerald M,, O’Donnell D,, Parsons LM,, Salfinger M . 2001. Lessons from a proficiency testing event for acid-fast microscopy. Chest 120 : 250– 257.[CrossRef] [PubMed]
40. Ba F,, Rieder HL . 1999. A comparison of fluorescence microscopy with the Ziehl-Neelsen technique in the examination of sputum for acid-fast bacilli. Int J Tuberc Lung Dis 3 : 1101– 1105.[PubMed]
41. Steingart KR,, Ng V,, Henry M,, Hopewell PC,, Ramsay A,, Cunningham J,, Urbanczik R,, Perkins MD,, Aziz MA,, Pai M . 2006. Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: a systematic review. Lancet Infect Dis 6 : 664– 674.[CrossRef]
42. Richards OW . 1941. The staining of acid-fast tubercle bacteria. Science 93 : 190.[CrossRef] [PubMed]
43. Hänscheid T,, Ribeiro CM,, Shapiro HM,, Perlmutter NG . 2007. Fluorescence microscopy for tuberculosis diagnosis. Lancet Infect Dis 7 : 236– 237.[CrossRef] [PubMed]
44. Bhalla M,, Sidiq Z,, Sharma PP,, Singhal R,, Myneedu VP,, Sarin R . 2013. Performance of light-emitting diode fluorescence microscope for diagnosis of tuberculosis. Int J Mycobacteriol 2 : 174– 178. [CrossRef] [PubMed]
45. Kumar VA,, Chandra PS . 2008. Auramine phenol staining of smears for screening acid fast bacilli in clinical specimens. J Commun Dis 40 : 47– 52.[PubMed]
46. Laifangbam S,, Singh HL,, Singh NB,, Devi KM,, Singh NT . 2009. A comparative study of fluorescent microscopy with Ziehl-Neelsen staining and culture for the diagnosis of pulmonary tuberculosis. Kathmandu Univ Med J KUMJ 7 : 226– 230. KUMJ. [PubMed]
47. Mutha A,, Tiwari S,, Khubnani H,, Mall S . 2005. Application of bleach method to improve sputum smear microscopy for the diagnosis of pulmonary tuberculosis. Indian J Pathol Microbiol 48 : 513– 517.[PubMed]
48. Burdash NM,, West ME,, Bannister ER,, Dyar C,, Duncan RC . 1976. Evaluation of a dual-staining method for acid-fast bacilli. J Clin Microbiol 2 : 149– 150.[PubMed]
49. International Agency for Research on Cancer . 1979. Monographs on the evaluation of carcinogenic risk of chemicals to humans. Chemicals and industrial processes associated with cancer in humans. IARC Monogr 1( Suppl.) : 24.
50. International Agency for Research on Cancer . 1982. Chemicals, industrial processes and industries associated with cancer in humans. an updating of Volumes 1 to 29. IARC Monogr 4( Suppl.) : 14.
51. Katila ML,, Mäntyjärvi RA . 1982. Acridine orange staining of smears for demonstration of Mycobacterium tuberculosis . Eur J Clin Microbiol 1 : 351– 353.[CrossRef] [PubMed]
52. Mallassez L,, Vignal W . 1883. Tuberculose zoologique. Arch Physiol Norm Pathologique 2 : 369– 412.
53. Miller FR . 1932. The induced development of non-acid-fast forms of bacillus tuberculosis and other mycobacteria. J Exp Med 56 : 411– 424.[CrossRef] [PubMed]
54. Miller FR . 1931. Non-acid-fast tubercle bacilli. Science 74 : 343– 344. [CrossRef] [PubMed]
55. Leonard WM . 1910. The paradox of the tubercle bacillus. Boston Med Surg J 162 : 753– 757.
56. Khomenko AG . 1987. The variability of Mycobacterium tuberculosis in patients with cavitary pulmonary tuberculosis in the course of chemotherapy. Tubercle 68 : 243– 253.[CrossRef]
57. Csillag A . 1964. The mycococcus form of mycobacteria. Microbiology 34 : 341– 352.
58. Much DH . 1907. Über die granuläre, nach Ziehl nicht färbbare Form des Tuberkulosevirus. Beitr Klin Tuberk 8 : 85– 99.[CrossRef]
59. Ulrichs T,, Lefmann M,, Reich M,, Morawietz L,, Roth A,, Brinkmann V,, Kosmiadi GA,, Seiler P,, Aichele P,, Hahn H,, Krenn V,, Göbel UB,, Kaufmann SHE . 2005. Modified immunohistological staining allows detection of Ziehl-Neelsen-negative Mycobacterium tuberculosis organisms and their precise localization in human tissue. J Pathol 205 : 633– 640.[CrossRef]
60. Ryan GJ,, Shapiro HM,, Lenaerts AJ . 2014. Improving acid-fast fluorescent staining for the detection of mycobacteria using a new nucleic acid staining approach. Tuberculosis (Edinb) 94 : 511– 518. [CrossRef] [PubMed]
61. St Amand AL,, Frank DN,, De Groote MA,, Basaraba RJ,, Orme IM,, Pace NR . 2005. Use of specific rRNA oligonucleotide probes for microscopic detection of Mycobacterium tuberculosis in culture and tissue specimens. J Clin Microbiol 43 : 5369– 5371. [CrossRef]
62. Fenhalls G,, Stevens L,, Moses L,, Bezuidenhout J,, Betts JC,, van Helden P,, Lukey PT,, Duncan K . 2002. In situ detection of Mycobacterium tuberculosis transcripts in human lung granulomas reveals differential gene expression in necrotic lesions. Infect Immun 70 : 6330– 6338.[CrossRef] [PubMed]
63. Harada K . 1976. The nature of mycobacterial acid-fastness. Stain Technol 51 : 255– 260.[CrossRef]
64. Goren MB,, Cernich M,, Brokl O . 1978. Some observations of mycobacterial acid-fastness. Am Rev Respir Dis 118 : 151– 154.[PubMed]
65. Oster G . 1951. Fluorescence of auramine O in the presence of nucleic acid. C R Hebd Seances Acad Sci 232 : 1708– 1710. (In French.)[PubMed]
66. Bhatt A,, Molle V,, Besra GS,, Jacobs WR Jr,, Kremer L . 2007. The Mycobacterium tuberculosis FAS-II condensing enzymes: their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development. Mol Microbiol 64 : 1442– 1454.[CrossRef]
67. Gao L-Y,, Laval F,, Lawson EH,, Groger RK,, Woodruff A,, Morisaki JH,, Cox JS,, Daffe M,, Brown EJ . 2003. Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy. Mol Microbiol 49 : 1547– 1563. [CrossRef]
68. Yamada H,, Bhatt A,, Danev R,, Fujiwara N,, Maeda S,, Mitarai S,, Chikamatsu K,, Aono A,, Nitta K,, Jacobs WR Jr,, Nagayama K . 2012. Non-acid-fastness in Mycobacterium tuberculosis ΔkasB mutant correlates with the cell envelope electron density. Tuberculosis (Edinb) 92 : 351– 357.[CrossRef]
69. Molle V,, Kremer L . 2010. Division and cell envelope regulation by Ser/Thr phosphorylation: Mycobacterium shows the way. Mol Microbiol 75 : 1064– 1077.[CrossRef]
70. Molle V,, Brown AK,, Besra GS,, Cozzone AJ,, Kremer L . 2006. The condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation. J Biol Chem 281 : 30094– 30103.[CrossRef]
71. Veyron-Churlet R,, Zanella-Cléon I,, Cohen-Gonsaud M,, Molle V,, Kremer L . 2010. Phosphorylation of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein reductase MabA regulates mycolic acid biosynthesis. J Biol Chem 285 : 12714– 12725.[CrossRef]
72. Molle V,, Gulten G,, Vilchèze C,, Veyron-Churlet R,, Zanella-Cléon I,, Sacchettini JC,, Jacobs WR Jr,, Kremer L . 2010. Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis . Mol Microbiol 78 : 1591– 1605.[CrossRef]
73. Slama N,, Leiba J,, Eynard N,, Daffé M,, Kremer L,, Quémard A,, Molle V . 2011. Negative regulation by Ser/Thr phosphorylation of HadAB and HadBC dehydratases from Mycobacterium tuberculosis type II fatty acid synthase system. Biochem Biophys Res Commun 412 : 401– 406.[CrossRef] [PubMed]
74. Khan S,, Nagarajan SN,, Parikh A,, Samantaray S,, Singh A,, Kumar D,, Roy RP,, Bhatt A,, Nandicoori VK . 2010. Phosphorylation of enoyl-acyl carrier protein reductase InhA impacts mycobacterial growth and survival. J Biol Chem 285 : 37860– 37871.[CrossRef]
75. Vilchèze C,, Molle V,, Carrère-Kremer S,, Leiba J,, Mourey L,, Shenai S,, Baronian G,, Tufariello J,, Hartman T,, Veyron-Churlet R,, Trivelli X,, Tiwari S,, Weinrick B,, Alland D,, Guérardel Y,, Jacobs WR Jr,, Kremer L . 2014. Phosphorylation of KasB regulates virulence and acid-fastness in Mycobacterium tuberculosis . PLoS Pathog 10 : e1004115.[CrossRef]
76. Huang CC,, Smith CV,, Glickman MS,, Jacobs WR Jr,, Sacchettini JC . 2002. Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis . J Biol Chem 277 : 11559– 11569.[CrossRef] [PubMed]
77. Barkan D,, Liu Z,, Sacchettini JC,, Glickman MS . 2009. Mycolic acid cyclopropanation is essential for viability, drug resistance, and cell wall integrity of Mycobacterium tuberculosis . Chem Biol 16 : 499– 509.[CrossRef] [PubMed]
78. Ryndak M,, Wang S,, Smith I . 2008. PhoP, a key player in Mycobacterium tuberculosis virulence. Trends Microbiol 16 : 528– 534.[CrossRef] [PubMed]
79. Gonzalo Asensio J,, Maia C,, Ferrer NL,, Barilone N,, Laval F,, Soto CY,, Winter N,, Daffé M,, Gicquel B,, Martín C,, Jackson M . 2006. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis . J Biol Chem 281 : 1313– 1316.[CrossRef]
80. Sena CBC,, Fukuda T,, Miyanagi K,, Matsumoto S,, Kobayashi K,, Murakami Y,, Maeda Y,, Kinoshita T,, Morita YS . 2010. Controlled expression of branch-forming mannosyltransferase is critical for mycobacterial lipoarabinomannan biosynthesis. J Biol Chem 285 : 13326– 13336. [CrossRef]
81. Peyron P,, Vaubourgeix J,, Poquet Y,, Levillain F,, Botanch C,, Bardou F,, Daffé M,, Emile J-F,, Marchou B,, Cardona P-J,, de Chastellier C,, Altare F . 2008. Foamy macrophages from tuberculous patients’ granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog 4 : e1000204.[CrossRef]
82. Russell DG,, Cardona P-J,, Kim M-J,, Allain S,, Altare F . 2009. Foamy macrophages and the progression of the human tuberculosis granuloma. Nat Immunol 10 : 943– 948.[CrossRef] [PubMed]
83. Daniel J,, Maamar H,, Deb C,, Sirakova TD,, Kolattukudy PE . 2011. Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages. PLoS Pathog 7 : e1002093.[CrossRef]
84. Kapoor N,, Pawar S,, Sirakova TD,, Deb C,, Warren WL,, Kolattukudy PE . 2013. Human granuloma in vitro model, for TB dormancy and resuscitation. PLoS One 8 : e53657.[CrossRef] [PubMed] [CrossRef]
85. Caire-Brändli I,, Papadopoulos A,, Malaga W,, Marais D,, Canaan S,, Thilo L,, de Chastellier C,, Flynn JL . 2014. Reversible lipid accumulation and associated division arrest of Mycobacterium avium in lipoprotein-induced foamy macrophages may resemble key events during latency and reactivation of tuberculosis. Infect Immun 82 : 476– 490.[CrossRef] [PubMed]
86. Garton NJ,, Christensen H,, Minnikin DE,, Adegbola RA,, Barer MR . 2002. Intracellular lipophilic inclusions of mycobacteria in vitro and in sputum. Microbiology 148 : 2951– 2958.[CrossRef]
87. Garton NJ,, Waddell SJ,, Sherratt AL,, Lee S-M,, Smith RJ,, Senner C,, Hinds J,, Rajakumar K,, Adegbola RA,, Besra GS,, Butcher PD,, Barer MR . 2008. Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum. PLoS Med 5 : e75.[CrossRef]
88. Dedieu L,, Serveau-Avesque C,, Kremer L,, Canaan S . 2013. Mycobacterial lipolytic enzymes: a gold mine for tuberculosis research. Biochimie 95 : 66– 73.[CrossRef] [PubMed]
89. Daleke MH,, Cascioferro A,, de Punder K,, Ummels R,, Abdallah AM,, van der Wel N,, Peters PJ,, Luirink J,, Manganelli R,, Bitter W . 2011. Conserved pro-Glu (PE) and Pro-Pro-Glu (PPE) protein domains target LipY lipases of pathogenic mycobacteria to the cell surface via the ESX-5 pathway. J Biol Chem 286 : 19024– 19034.[CrossRef]
90. Dhouib R,, Laval F,, Carrière F,, Daffé M,, Canaan S . 2010. A monoacylglycerol lipase from Mycobacterium smegmatis involved in bacterial cell interaction. J Bacteriol 192 : 4776– 4785.[CrossRef] [PubMed]
91. Deb C,, Daniel J,, Sirakova TD,, Abomoelak B,, Dubey VS,, Kolattukudy PE . 2006. A novel lipase belonging to the hormone-sensitive lipase family induced under starvation to utilize stored triacylglycerol in Mycobacterium tuberculosis . J Biol Chem 281 : 3866– 3875.[CrossRef] [PubMed]
92. Mishra KC,, de Chastellier C,, Narayana Y,, Bifani P,, Brown AK,, Besra GS,, Katoch VM,, Joshi B,, Balaji KN,, Kremer L . 2008. Functional role of the PE domain and immunogenicity of the Mycobacterium tuberculosis triacylglycerol hydrolase LipY. Infect Immun 76 : 127– 140.[CrossRef] [PubMed]
93. Low KL,, Rao PS,, Shui G,, Bendt AK,, Pethe K,, Dick T,, Wenk MR . 2009. Triacylglycerol utilization is required for regrowth of in vitro hypoxic nonreplicating Mycobacterium bovis bacillus Calmette-Guerin. J Bacteriol 191 : 5037– 5043.[CrossRef]
94. Deb C,, Lee C-M,, Dubey VS,, Daniel J,, Abomoelak B,, Sirakova TD,, Pawar S,, Rogers L,, Kolattukudy PE . 2009. A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen. PLoS One 4 : e6077.[CrossRef]
95. Daniel J,, Deb C,, Dubey VS,, Sirakova TD,, Abomoelak B,, Morbidoni HR,, Kolattukudy PE . 2004. Induction of a novel class of diacylglycerol acyltransferases and triacylglycerol accumulation in Mycobacterium tuberculosis as it goes into a dormancy-like state in culture. J Bacteriol 186 : 5017– 5030.[CrossRef]
96. Sirakova TD,, Dubey VS,, Deb C,, Daniel J,, Korotkova TA,, Abomoelak B,, Kolattukudy PE . 2006. Identification of a diacylglycerol acyltransferase gene involved in accumulation of triacylglycerol in Mycobacterium tuberculosis under stress. Microbiology 152 : 2717– 2725.[CrossRef] [PubMed]
97. Cunningham AF,, Spreadbury CL . 1998. Mycobacterial stationary phase induced by low oxygen tension: cell wall thickening and localization of the 16-kilodalton alpha-crystallin homolog. J Bacteriol 180 : 801– 808.[PubMed]
98. Bhamidi S,, Scherman MS,, Jones V,, Crick DC,, Belisle JT,, Brennan PJ,, McNeil MR . 2011. Detailed structural and quantitative analysis reveals the spatial organization of the cell walls of in vivo grown Mycobacterium leprae and in vitro grown Mycobacterium tuberculosis . J Biol Chem 286 : 23168– 23177.[CrossRef]
99. Obregon-Henao A,, Shanley CA,, Shang S,, Caraway ML,, Basaraba RJ,, Duncan CG,, Ordway DJ,, Orme IM . 2012. Cortisone-forced reactivation of weakly acid fast positive Mycobacterium tuberculosis in guinea pigs previously treated with chemotherapy. Mycobact Dis 2 : 116.
100. Ryan GJ,, Hoff DR,, Driver ER,, Voskuil MI,, Gonzalez-Juarrero M,, Basaraba RJ,, Crick DC,, Spencer JS,, Lenaerts AJ . 2010. Multiple M. tuberculosis phenotypes in mouse and guinea pig lung tissue revealed by a dual-staining approach. PLoS One 5 : e11108.[CrossRef]

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