Bacterial Inclusion Bodies: Discovering Their Better Half

© 2017 Elsevier Ltd Bacterial inclusion bodies (IBs) are functional, non-toxic amyloids occurring in recombinant bacteria showing analogies with secretory granules of the mammalian endocrine system. The scientific interest in these mesoscale protein aggregates has been historically masked by their status as a hurdle in recombinant protein production. However, progressive understanding of how the cell handles the quality of recombinant polypeptides and the main features of their intriguing molecular organization has stimulated the interest in inclusion bodies and spurred their use in diverse technological fields. The engineering and tailoring of IBs as functional protein particles for materials science and biomedicine is a good example of how formerly undesired bacterial byproducts can be rediscovered as promising functional materials for a broad spectrum of applications. Bacterial IBs are mesoscale protein aggregates commonly observed in recombinant bacteria, primarily formed by recombinant protein. IBs create a bottleneck for the production of soluble protein species, and many genetic and process-based strategies have been developed to minimize their formation. The recombinant protein in IBs is partially found in an amyloidal form, which entraps non-amyloidal functional protein and offers mechanical stability. IBs naturally penetrate mammalian cells, and can be targeted to specific receptors. Upon internalization, functional protein is released, mimicking the function of secretory granules from the mammalian endocrine system. The applications of IBs as functional materials are increasing and include roles as reusable catalysts, drug delivery systems, and functional topographies in tissue engineering. The production of IBs in endotoxin-free microorganisms may extend these and additional uses.