Secretome Dynamics in a Gram-Positive Bacterial Model[S]

Tsolis et al., reveal that the regulation of protein secretion in a Gram positive bacterial model is complex. Some of this regulation is transcriptional but a lot occurs post-transcriptionally and affects different exported proteins in different ways. Main Sec and chaperone machineries are not part of this regulation. [Display omitted] Highlights •Stable and variable secretomes detected in a Gram+ bacterial model.•Quantitative and qualitative changes to a secretome subset.•Transcriptional regulation but not export machinery levels account for secretome changes.•Unknown post-transcriptional mechanisms link metabolism to secretion. Protein secretion is a central biological process in all organisms. Most studies dissecting bacterial secretion mechanisms have focused on Gram-negative cell envelopes such as that of Escherichia coli. However, proteomics analyses in Gram negatives is hampered by their outer membrane. Here we studied protein secretion in the Gram-positive bacterium Streptomyces lividans TK24, in which most of the secretome is released in the growth medium. We monitored changes of the secretome as a function of growth phase and medium. We determined distinct protein classes of “house-keeping” secreted proteins that do not change their appearance or abundance in the various media and growth phases. These comprise mainly enzymes involved in cell wall maintenance and basic transport. In addition, we detected significant abundance and content changes to a sub-set of the proteome, as a function of growth in the different media. These did not depend on the media being minimal or rich. Transcriptional regulation but not changes in export machinery components can explain some of these changes. However, additional downstream mechanisms must be important for selective secretome funneling. These observations lay the foundations of using S. lividans as a model organism to study how metabolism is linked to optimal secretion and help develop rational optimization of heterologous protein production.