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Background  The development of new drugs against tuberculosis and diphtheria is focused on disrupting the biogenesis of the cell wall, the unique architecture of which confers resistance against current therapies. The enzymatic pathways involved in the synthesis of the cell wall by these pathogens are well understood, but the underlying regulatory mechanisms are largely unknown.    Results  Here, we characterize IpsA, a LacI-type transcriptional regulator conserved among  Mycobacteria  and  Corynebacteria  that plays a role in the regulation of cell wall biogenesis. IpsA triggers  myo -inositol formation by activating  ino1 , which encodes inositol phosphate synthase. An  ipsA  deletion mutant of  Corynebacterium glutamicum  cultured on glucose displayed significantly impaired growth and presented an elongated cell morphology. Further studies revealed the absence of inositol-derived lipids in the cell wall and a complete loss of mycothiol biosynthesis. The phenotype of the  C. glutamicum ipsA  deletion mutant was complemented to different extend by homologs from  Corynebacterium diphtheriae  (dip1969) and  Mycobacterium tuberculosis  (rv3575), indicating the conserved function of IpsA in the pathogenic species. Additional targets of IpsA with putative functions in cell wall biogenesis were identified and IpsA was shown to bind to a conserved palindromic motif within the corresponding promoter regions.  Myo -inositol was identified as an effector of IpsA, causing the dissociation of the IpsA-DNA complex  in vitro .    Conclusions  This characterization of IpsA function and of its regulon sheds light on the complex transcriptional control of cell wall biogenesis in the mycolata taxon and generates novel targets for drug development.

IpsA, a novel LacI-type regulator, is required for inositol-derived lipid formation in Corynebacteria and Mycobacteria