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Covering: up to the end of 2022 In recent years rare Actinobacteria have become increasingly recognised as a rich source of novel bioactive metabolites. Actinomadura are Gram-positive bacteria that occupy a wide range of ecological niches. This review highlights about 230 secondary metabolites produced by Actinomadura spp., reported until the end of 2022, including their bioactivities and selected biosynthetic pathways. Notably, the bioactive compounds produced by Actinomadura spp. demonstrate a wide range of activities, including antimicrobial, antitumor and anticoccidial effects, highlighting their potential in various fields. [ABSTRACT FROM AUTHOR]

Bacterial cells are surrounded by a peptidoglycan (PG) wall, which is a crucial target for antibiotics. It is well known that treatment with cell wall-active antibiotics occasionally converts bacteria to a non-walled "L-form" state that requires the loss of cell wall integrity. L-forms may have an important role in antibiotic resistance and recurrent infection. Recent work has revealed that inhibition of de novo PG precursor synthesis efficiently induces the L-form conversion in a wide range of bacteria, but the molecular mechanisms remain poorly understood. Growth of walled bacteria requires the orderly expansion of the PG layer, which involves the concerted action not just of synthases but also degradative enzymes called autolysins. Most rod-shaped bacteria have two complementary systems for PG insertion, the Rod and aPBP systems. Bacillus subtilis has two major autolysins, called LytE and CwlO, which are thought to have partially redundant functions. We have dissected the functions of autolysins, relative to the Rod and aPBP systems, during the switch to L-form state. Our results suggest that when de novo PG precursor synthesis is inhibited, residual PG synthesis occurs specifically via the aPBP pathway, and that this is required for continued autolytic activity by LytE/CwlO, resulting in cell bulging and efficient L-form emergence. The failure of L-form generation in cells lacking aPBPs was rescued by enhancing the Rod system and in this case, emergence specifically required LytE but was not associated with cell bulging. Our results suggest that two distinct pathways of L-form emergence exist depending on whether PG synthesis is being supported by the aPBP or RodA PG synthases. This work provides new insights into mechanisms of L-form generation, and specialisation in the roles of essential autolysins in relation to the recently recognised dual PG synthetic systems of bacteria. [ABSTRACT FROM AUTHOR]

Spore formation in Bacillus subtilis is a superb experimental system with which to study some of the most fundamental problems of cellular development and differentiation. Work begun in the 1980s and ongoing today has led to an impressive understanding of the temporal and spatial regulation of sporulation, and the functions of many of the several hundred genes involved. Early in sporulation the cells divide in an unusual asymmetrical manner, to produce a small prespore cell and a much larger mother cell. Aside from developmental biology, this modified division has turned out to be a powerful system for investigation of cell cycle mechanisms, including the components of the division machine, how the machine is correctly positioned in the cell, and how division is coordinated with replication and segregation of the chromosome. Insights into these fundamental mechanisms have provided opportunities for the discovery and development of novel antibiotics. This review summarizes how the bacterial cell cycle field has developed over the last 20 or so years, focusing on opportunities emerging from the B. subtilis system. DOI 10.1099/mic.0.035634-0

The prokaryotic cytoskeletal protein MreB is thought to govern cell shape by positioning the cell wall synthetic apparatus at growth sites in the cell. In rod-shaped bacteria it forms helical filaments that run around the periphery of the rod during elongation. Gram-positive bacteria often contain more than one mreB gene. Bacillus subtilis has three mreB-like genes, mreB, mbl and mreBH, the first two of which have been shown to be essential under normal growth conditions. Expression of an mreB homologue from the closely related organism Bacillus licheniformis did not have any effect on cell growth or morphology. In contrast, expression of mreB from the phylogenetically more distant bacterium Clostridium perfringens produced shape defects and ultimately cell death, due to disruption of the endogenous MreB cytoskeleton. However, expression of either [mreB.sup.B] licheniformis ([mreB.sup.BI]) or [mreB.sup.C perfringens] ([mreB.sup.Cp]) was sufficient to confer a rod shape to B. subtilis deleted for the three mreB isologues, supporting the idea that the three proteins have largely redundant functions in cell morphogenesis. Expression of [mreBCD.sup.BI] could fully compensate for the loss of mreBCD in B. subtilis and led to the formation of rod-shaped cells. In contrast, expression of [mreBCD.sup.Cp] was not sufficient to confer a rod shape to B. subtilis [DELTA]mreBCD, indicating that a complex of these three cell shape determinants is not enough for cell morphogenesis of B. subtilis. DOI 10.1099/mic.0.030692-0

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.02.035 Byline: Stephan Gruber (1), Jeff Errington (1) Keywords: CELLBIO; CELLCYCLE; MICROBIO Abstract: Proper segregation of DNA replication products is essential in all cells. In Bacillus subtilis, two protein complexes have been implicated in this process: the ParAB homologs, Soj and Spo0J, and the bacterial Smc/ScpAB complex, also called condensin. Here we demonstrate that Smc is highly enriched in the region around the origin of replication, specifically near parS sites to which Spo0J binds and at highly transcribed genes. Furthermore, we find that efficient recruitment of Smc to a large region around the origin of replication depends on the presence of Spo0J. We show that Spo0J performs two independent functions: regulation of initiation of DNA replication via Soj and promotion of chromosome segregation by Smc recruitment. Our results demonstrate a direct functional interaction between two widely conserved systems involved in chromosome replication and segregation. Author Affiliation: (1) Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK Article History: Received 1 October 2008; Revised 23 December 2008; Accepted 19 February 2009 Article Note: (miscellaneous) Published: May 14, 2009

Bacterial actin homologues are thought to have a role in cell shape determination by positioning the cell wall synthetic machinery. They are also thought to control other functions, including cell polarity and chromosome segregation in various organisms. Bacillus subtilis and many other gram-positive bacteria have three actin isoforms, MreB, Mbl, and MreBH, which colocalize in helical structures that span the length of the cell, close to the inner surface of the cytoplasmic membrane. Deletion of the mbl gene has previously been reported to produce viable, although poorly growing, mutant cells. We now show that under normal conditions [DELTA]mbl ceils are nonviable but suppressors allowing growth readily accumulate. In the presence of high concentrations of [Mg.sup.2+], viable, nonsuppressed mutants can be obtained. A screen for suppressor mutations revealed that deletion of rsgI restores [Mg.sup.2+]-independent growth of the mbl mutant. Recent work has shown that rsgI deletion leads to upregulation of the alternative sigma factor [[sigma].sup.I]. The basis of suppression is not yet dear, but it is independent of the [Mg.sup.2+] effect. We found that the construction of a triple mutant lacking all three actin homologues became possible in the rsgI background. Triple mutant cells are spherical, but no significant defect in chromosome segregation was detected.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.07.044 Byline: Heath Murray (1), Jeff Errington (1) Keywords: CELLBIO; CELLCYCLE; MICROBIO Abstract: Regulation of DNA replication and segregation is essential for all cells. Orthologs of the plasmid partitioning genes parA, parB, and parS are present in bacterial genomes throughout the prokaryotic evolutionary tree and are required for accurate chromosome segregation. However, the mechanism(s) by which parABS genes ensure proper DNA segregation have remained unclear. Here we report that the ParA ortholog in B. subtilis (Soj) controls the activity of the DNA replication initiator protein DnaA. Subcellular localization of several Soj mutants indicates that Soj acts as a spatially regulated molecular switch, capable of either inhibiting or activating DnaA. We show that the classical effect of Soj inhibiting sporulation is an indirect consequence of its action on DnaA through activation of the Sda DNA replication checkpoint. These results suggest that the pleiotropy manifested by chromosomal parABS mutations could be the indirect effects of a primary activity regulating DNA replication initiation. Author Affiliation: (1) Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK Article History: Received 3 March 2008; Revised 25 May 2008; Accepted 31 July 2008 Article Note: (miscellaneous) Published: October 2, 2008