Letter | Published:

Mycobacterium microti may protect itself from intracellular destruction by releasing cyclic AMP into phagosomes

Abstract

PATHOGENIC mycobacteria are able to survive and multiply within macrophages. How they do this is not known, but recent quantitative electron microscope surveys of intracellular events in macrophages infected in vitro with either Mycobacterium tuberculosis or M. microti revealed a lack of discharge of lysosomes into phagosomes containing live bacilli, whereas dead bacilli were associated with discharged lysosomal contents within phagolysosomes1,2. Possibly the living bacteria produce a factor which inhibits fusion between phagosomal and lysosomal membranes and thereby prevent the discharge of putatively bactericidal lysosomal contents into the bacterial environment. Since high intracellular levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) mediate pharmacological inhibition of lysosomal discharge in leukocytes3,4 we reasoned that increased amounts of this nucleotide may occur in macrophages infected with living mycobacteria but not in those infected with dead ones. We report here experiments with M. microti showing that this is so and suggesting a bacterial origin for the addititional cyclic AMP.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Armstrong, J. A., and Hart, P. D' A., J. exp. Med., 134, 713–740 (1971).

  2. 2

    Hart, P. D' Arcy, Armstrong, J. A., Brown, C. A., and Draper, P., Infect. Immunity, 5, 803–807 (1972).

  3. 3

    Weissmann, G., Zurier, R. B., and Hoffstein, S., Am. J. Path., 68, 539–559 (1972).

  4. 4

    Zurier, R. B., Weissmann, G., Hoffstein, S., Kammerman, S., and Tai, H. H., J. clin. Invest., 53, 297–309 (1974).

  5. 5

    Giles, K. W., and Myers, A., Nature, 206, 93 (1965).

  6. 6

    Brown, B. L., Albano, J. D. M., Ekins, R. P., Spherzi, A. M., and Tampion, W., Biochem. J., 121, 561–562 (1971).

  7. 7

    Kuo, J. F., and Greengard, P., Adv. Cyclic Nucleotide Res., 2, 41–50 (1972).

  8. 8

    Kinyoun, J. J., Am. J. publ. Hlth, 5, 867 (1915).

  9. 9

    Stossel, T. P., Murad, F., Mason, R. J., and Vaughan, M., J. biol. Chem., 245, 6228–6234 (1970).

  10. 10

    Stolc, V., Biochim. biophys. Acta, 264, 285–288 (1972).

  11. 11

    Ignarro, L. J., and George, W. J., J. exp. Med., 140, 225–238 (1974).

  12. 12

    Draper, P., and Rees, R. J. W., Nature, 228, 860–861 (1970).

  13. 13

    Szabo, M., and Burke, G., Biochim. biophys. Acta, 264, 289–299 (1972).

  14. 14

    Jones, T. C., and Hirsch, J. G., J. exp. Med., 136, 1173–1194 (1972).

  15. 15

    Friis, R. R., J. Bact., 110, 706–721 (1972).

  16. 16

    Novotny, P., Short, A. L., and Turner, W. H., Proc. Soc. gen. Microbiol., 2, 18 (1974).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.