AUTHOR=Klotz Courtney , Barrangou Rodolphe TITLE=Engineering Components of the Lactobacillus S-Layer for Biotherapeutic Applications JOURNAL=Frontiers in Microbiology VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02264 DOI=10.3389/fmicb.2018.02264 ISSN=1664-302X ABSTRACT=Lactic acid bacteria (LAB) are frequently harnessed for the delivery of biomolecules to mucosal tissues. Several species of Lactobacillus are commonly employed for this task, of which a subset are known to possess surface-layers (S-layers). The S-layer is a two-dimensional crystalline array of repeating proteinaceous subunits that forms the outermost coating of many prokaryotic cell envelopes. Its periodicity and abundance have made it a target for numerous biotechnological applications, including delivery of therapeutic proteins and vaccine antigens. In the following review, we examine the multi-faceted S-layer protein (Slp), and its use in both heterologous protein expression and mucosal vaccine delivery, through its diverse genetic components: the strong native promoter, capable of synthesizing as many as 500 Slp subunits per second; the signal peptide that stimulates robust secretion of target proteins; and the structural domains, which can be harnessed for both cell surface display of a foreign peptide or adhesion enhancement of a host bacterium. Although numerous studies have established vaccine platforms based on one or more components of the Lactobacillus S-layer, this area of research remains largely in its infancy, thus this review not only highlights past works, but also advocates for the future use of Slps in mucosal vaccine research.