KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally.

Two-component systems, consisting of a histidine kinase and a response regulator, serve signal transduction in bacteria, often regulating transcription in response to environmental stimuli. Here, we identify a tandem serine histidine kinase function for KdpD, previously described as a histidine kinase of the KdpDE two-component system, which controls production of the potassium pump KdpFABC. We show that KdpD additionally mediates an inhibitory serine phosphorylation of KdpFABC at high potassium levels, using not its C-terminal histidine kinase domain but an N-terminal atypical serine kinase domain. Sequence analysis of KdpDs from different species highlights that some KdpDs are much shorter than others. We show that, while Escherichia coli KdpD's atypical serine kinase domain responds directly to potassium levels, a shorter version from Deinococcus geothermalis is controlled by second messenger cyclic di-AMP. Our findings add to the growing functional diversity of sensor kinases while simultaneously expanding the framework for regulatory mechanisms in bacterial potassium homeostasis.

Severe Refractory Paraneoplastic Mucous Membrane Pemphigoid Successfully Treated With Rituximab.

Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease of the mucous membranes, which can cause irreversible scarring and is discussed to be associated with cancer, if laminin-332-autoantibodies are present. MMP with severe ocular and laryngeal involvement is difficult to treat and can be treatment-refractory to conventional immunosuppressant therapy. A 67-year-old man with a history of prostate cancer presented to our clinic with sore throat, intraoral bullae, odynophagia, dysphonia, exertional dyspnea, and erosions of the glans penis. Clinical examination confirmed a laryngo-pharyngitis with involvement of the epiglottis and bilateral symblepharon. Diagnostics comprising multiple biopsies, direct and indirect immunofluorescence, serology analysis, and immunoblotting confirmed the diagnosis of a paraneoplastic MMP by showing a subepithelial split in histology and the presence of anti-laminin-332-antibodies. Despite combined systemic treatment with prednisolone and either dapsone or azathioprine, a progress of the disease occurred leading to severe ocular and laryngeal complications. Two month after rituximab treatment, complete disease control was achieved. This case report shows a severe ocular and life threatening laryngeal involvement of therapy-refractory paraneoplastic MMP highlighting the importance of interdisciplinary management and difficulty of diagnosing MMP despite repeated diagnostic testing.