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

Summary The 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. The WhiB‐like (Wbl) family of proteins are exclusively found in Actinobacteria, with roles in virulence, antibiotic resistance and in the regulation of morphological differentiation. Here I summarise recent research in Mycobacteria, Corynebacteria and Streptomyces, highlight emerging themes and provide perspectives for future research.