The Microbes inside Us and the Race for Colibactin.

Abstract

The human body is composed of about 200 different cell types (http://www.bioon.com/book/biology/mboc/mboc.cgi@ code= 220801800040279.htm), with overall 10 cells making up the different tissues and organs, such as brain, skin, liver, and blood vessels. Although these numbers highlight at the same time the simplicity and the complexity of the human body, with its underlying biochemistry and cell–cell communication leading to multicellularity, they are nothing compared to the number and diversity of bacteria living in and on humans. Conservative estimations assume at least 2000 different species of bacteria with a total number of 10 (ten times more than human cells) microbial cells on each human body (http://hmpdacc.org). They are essential for digesting food, training the immune system, protecting us against “bad” microbes by occupying their infection niche, and producing vitamins (e.g., biotin or vitamin K). Gut microbes in particular are generally regarded as beneficial to our health, and there is increasing evidence that the gut microbiome can even influence neurological outcomes such as behavior or the onset or severity of disorders of the nervous system. The mammalian immune system, which is generally thought to be designed to control microorganisms, might in fact be developed and controlled by the gut mibrobiome. With the development of modern sequencing technology, it has become obvious that not only does the organismic diversity of our microbiome exceed that of human cell types, but the number of microbial genes is also several hundred times greater than that of human genes. These genes include small-molecule biosynthetic gene clusters (BGCs) that are involved in the biosynthesis of typical macrolide polyketides, nonribosomal peptides, or ribosomally encoded and posttranslationally modified peptides (RiPPs). An example is the thiopeptide lactocillin (1), derivatives of which are currently in clinical trials as antibiotics. Thus it seems likely that drugs produced by our own microbiota also contribute to our health. On the other hand, an imbalance of symbionts (health-promoting bacteria), commensals (permanent residents with no benefit or detriment to the host), and pathobionts (pathogens), which is termed ÐdysbiosisÏ, can be directly correlated to obesity, diabetes, inflammation diseases like CrohnÏs disease, and even cancer. Although the underlying mechanisms are just beginning to be revealed, there are several recent examples to suggest that typical natural products might also play a major role in these processes. Tilivalline (2), a pyrrolobenzodiazepine cytotoxin, is synthesized by a nonribosomal peptide synthetase (NRPS) in Klebsiella oxytoca. K. oxytoca is the causative agent of antibiotic-associated hemorrhagic colitis (AAHC), a disease associated with antibiotic-driven enterobacterial overgrowth by K. oxytoca. This bacterium is a resident of the gut in 2– 10% of healthy individuals and upon antibiotic therapy, it might be able to dominate the gut microbiome, thereby resulting in tilivalline-induced apoptosis and disrupted epithelial barrier function, which can ultimately lead to colitis. [*] Prof. Dr. H. B. Bode Merck Stiftungsprofessur fír Molekulare Biotechnologie Fachbereich Biowissenschaften, Goethe Universit•t Frankfurt Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany) and Buchmann Institute for Molecular Life Sciences (BMLS) Goethe Universit•t Frankfurt Max-von-Laue-Str. 15, 60438 Frankfurt a. M. (Germany) E-mail: h.bode@bio.uni-frankfurt.de Homepage: http://www.uni-frankfurt.de/fb/fb15/institute/inst-3mol-biowiss/AK-Bode

DOI: 10.1002/anie.201505341

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Cite this paper

@article{Bode2015TheMI, title={The Microbes inside Us and the Race for Colibactin.}, author={Helge B Bode}, journal={Angewandte Chemie}, year={2015}, volume={54 36}, pages={10408-11} }