Pre-sporulation stages of Streptomyces differentiation: state-of-the-art and future perspectives

Abstract

Streptomycetes comprise very important industrial bacteria, producing two-thirds of all clinically relevant secondary metabolites. They are mycelial microorganisms with complex developmental cycles that include programmed cell death (PCD) and sporulation. Industrial fermentations are usually performed in liquid cultures (large bioreactors), conditions in which Streptomyces strains generally do not sporulate, and it was traditionally assumed that there was no differentiation. In this work, we review the current knowledge on Streptomyces pre-sporulation stages of Streptomyces differentiation.

Fig. 1

Streptomyces developmental cycle and mycelium differentiation. (a) Streptomyces developmental cycle in liquid (left) and solid (right) cultures. Newly described structures and the proposed nomenclature (Manteca et al., 2005) are indicated in red: MI, first compartmentalized mycelium; MII, second multinucleated mycelium. Classical nomenclature (substrate and aerial mycelium) and hydrophobic layers are also indicated. PCD, programmed cell death. (b) Different types of mycelia observed under the confocal and electron microscopes. Upper panels, confocal images. Left, MI young compartmentalized hypha (notice the original spore in the right side) stained with membrane stain FM 4-64; mycelium is fully compartmentalized and compartments are separated by membranes (arrows). Centre, MII multinucleated hypha stained with the cell wall stain WGA. Right, sporulated hypha stained with WGA; notice thick cell wall septa separating spores. Some of the septa are indicated by arrows. Figure adapted from Manteca et al. (2006a, 2010b).

Fig. 2

Biochemical pathways regulating Streptomyces differentiation. Pathways involved in hydrophobic covers formation (‘bald’, ‘sky’) and sporulation (‘whi’, ‘septation’) are illustrated. New developmental stages (MI/MII; Manteca et al., 2005) and presporulation pathways (‘MI/MII transition’) switching on secondary metabolite production are indicated in red.

Fig. 3

Proposed developmental model for Streptomyces growing in natural soils. Mycelial structures (MI, first mycelium; MII, second mycelium), vegetative and reproductive phases, and PCD are indicated. The vegetative phase is the predominant one. See text for details.