The actinobacterial WhiB‐like (Wbl) family of transcription factors

Abstract

SummaryThe WhiB‐like (Wbl) family of proteins are exclusively found in Actinobacteria. Wbls have been shown to play key roles in virulence and antibiotic resistance in Mycobacteria and Corynebacteria, reflecting their importance during infection by the human pathogens Mycobacterium tuberculosis, Mycobacterium leprae and Corynebacterium diphtheriae. In the antibiotic‐producing Streptomyces, several Wbls have important roles in the regulation of morphological differentiation, including WhiB, a protein that controls the initiation of sporulation septation and the founding member of the Wbl family. In recent years, genome sequencing has revealed the prevalence of Wbl paralogues in species throughout the Actinobacteria. Wbl proteins are small (generally ~80–140 residues) and each contains four invariant cysteine residues that bind an O2‐ and NO‐sensitive [4Fe–4S] cluster, raising the question as to how they can maintain distinct cellular functions within a given species. Despite their discovery over 25 years ago, the Wbl protein family has largely remained enigmatic. Here I summarise recent research in Mycobacteria, Corynebacteria and Streptomyces that sheds light on the biochemical function of Wbls as transcription factors and as potential sensors of O2 and NO. I suggest that Wbl evolution has created diversity in protein–protein interactions, [4Fe–4S] cluster‐sensitivity and the ability to bind DNA.

A Novel AdpA Homologue Negatively Regulates Morphological Differentiation in Streptomyces xiamenensis 318

“…Our results showed that AdpA Sx negatively affects cell growth and morphological differentiation in S. xiamenensis 318. Electrophoretic mobility shift assays (EMSAs) were therefore performed on several putative AdpA Sx targets involved in cell growth and morphological differentiation: ssgA (sxim_03860), encoding a putative membrane protein homologous to ssgB of Streptomyces coelicolor (31); ftsZ (sxim_10220), encoding a putative cell division protein; ftsH (sxim_23050), encoding a putative cell division GTPase; amfC (sxim_30820), encoding an aerial mycelium-associated protein (32); sxim_18210 (whiB), sxim_19730 (wblA1), sxim_24890 (wblA2), and sxim_39910 (wblE), encoding WhiB-family proteins that regulate morphological differentiation (33,34); sxim_29740, encoding a sporulation-associated protein; bldA, encoding a UUA-reading tRNA-leucine (21); bldD (sxim_03450), encoding a pleiotropic negative regulator of morphological and physiological development; and bldG (sxim_41700), encoding an anti-antisigma factor homolog to BldG, which controls key developmental processes in S. coelicolor and S. griseus (35,36).…”

Mass Spectrometric Identification of [4Fe–4S](NO)x Intermediates of Nitric Oxide Sensing by Regulatory Iron–Sulfur Cluster Proteins

“…The same study showed that it forms a stable complex with the sigma factor SigA that is dependent on the cluster; reaction with NO led to dissociation of the complex and a form of WhiB1 that can bind its own promoter . Other M. tuberculosis Wbl proteins have been shown to interact with SigA, suggesting that Wbl proteins commonly function together with partner proteins …”

“…[7,14] Other M. tuberculosis Wbl proteins have been shown to interactw ith SigA, suggesting that Wbl proteins commonly function together with partner proteins. [15] The mechanismsb yw hich Fe-S regulatory proteins react with NO are not well characterized. Recent advances in techniques for Fe-S protein preparation and handling have facilitated studies by av ariety of methods that have demonstrated that multinuclear iron species similar to the well known inorganic complexes Roussin's Red Ester (RRE;[ Fe 2 (NO) 4 (SR) 2 ]) and Roussin's Black Salt (RBS;[ Fe 4 (NO) 7 (S) 3 ]) [16] (see Figure S1) are major products.…”

Differential transcription of expanded gene families in central carbon metabolism of Streptomyces coelicolor A3(2)

“…Such gene-family expansions are well known in streptomycete regulatory genes [7][8][9][10] and in specialized metabolite biosynthesis [11,12]. Yet, there has been limited attention focussed on the genes of central metabolism despite a number of gene-expansion events being identified from biochemical and phylogenomic studies.…”