Control of the growth of single-celled organisms such as bacteria and fungi is a constant problem. We wish to encourage their growth in the industrial preparation of alcohols and anti-cancer agents [1] and in our digestive systems where they produce vitamin K2 [2]. On the other hand, we also want to rid ourselves of them when they infect us. Some infections, like tuberculosis, continue to be a problem. The clinical approach to curing tuberculosis in humans itself is famous because of the innovation of using several drugs with different modes of action, simultaneously.

Sadly, even this approach does not work for para-tuberculosis, an incurable condition similar to tuberculosis that affects ruminants, including cattle. The infection is a problem both for animal welfare and food safety reasons [3].


Fig. An example of a phosphatidylinositol mannose lipid, PIM2.

The incurable nature of para-tuberculosis raises a real problem for us to solve. Furthermore, it is an inter-disciplinary research problem: there are elements of microbiology/mycology, animal farming, toxicology, chemistry and maybe even food science. The work of such an unholy mixture of backgrounds can be informed and possibly even inspired by the work of a group of a Japanese-British-German collaboration, that was published recently. Hanashima et al. have shown that there is an endogenous protein in mammals that binds to a major component of the membrane of mycobacteria [4]. This component is called phosphatidylinositol mannoside (PIM) and is really a collection of several similar compounds [5, 6] of which a simpler example is shown in the Fig.

The protein is called ZG16p and was initially discovered in the pancreas of rats and later in the digestive system of humans [7]. There is therefore a protein that may be involved in the immune response to para-tuberculosis in all of us and may provide the basis for continued research into ways of tackling these kinds of infection without using anti-biotics. What if similar proteins could be engineered for tackling other diseases? This may be part of an adequate response to the increasing ineffectiveness of anti-biotics. And perversely, tuberculosis may once again provide the inspiration for our approach to tackling infectious disease.


[1] H. Ueda, H. Nakajima, Y. Hori, T. Fujita, M. Nishimura, T. Goto, M. Okuhara, The Journal of Antibiotics, 1994, 47, 301-310. DOI: 10.7164/antibiotics.47.301

[2] R. Bentley and R. Meganathan, Microbiology Reviews, 1982, 46, 241–280.

[3] N. Sung, M. T. Collins, Applied Environmental Microbiology, 2000, 66, 1334–1339.

[4] S. Hanashima, S. Gçtze, Y. Liu, A. Ikeda, K. Kojima-Aikawa, N. Taniguchi, D. Varûn Silva, T. Feizi, P. H. Seeberger, Y. Yamaguchi, ChemBioChem, 2015, 16, 1502 – 1511. DOI: 10.1002/cbic.201500103

[5] Y. S. Morita, J. H. Patterson, H. Billman-Jacobe, M. J. Mcconville, Biochemical Journal, 2004, 378, 589–597. DOI: 10.1042/BJ20031372

[6] G. D. Sprott, C. J. Dicaire, K. Gurnani, S. Sad, L. Krishnan, Infection and Immunity, 2004, 72, 5235–5246. DOI: 10.1128/IAI.72.9.5235–5246.2004

[7] H. Tateno, R. Yabe, T. Sato, A. Shibazaki, T. Shikanai, T. Gonoi, H. Narimatsu, J. Hirabayashi, Glycobiology, 2012, 22, 210–220. DOI:10.1093/glycob/cwr130