Paraphimosis as a complication of monkeypox infection.

We discuss a case report of a 38-year-old uncircumcised male on pre-exposure prophylaxis for human immunodeficiency virus who presents to the emergency department for painful lesions over his penile region following unprotected sexual intercourse. Following the development of these lesions he developed painless, itchy pustules over his bilateral arms and back. He also had extensive pain and swelling over his penile region, which prevented him from unretracting his foreskin. Chlamydia trachomatis, Herpes simplex virus, Neisseria gonorrhoeae, and syphilis tests were negative. He was positive for orthopoxvirus using polymerase chain reaction. A diagnosis of paraphimosis as a complication of monkeypox infection was made.

Structural and functional studies of pyruvate carboxylase regulation by cyclic di-AMP in lactic acid bacteria.

Cyclic di-3',5'-adenosine monophosphate (c-di-AMP) is a broadly conserved bacterial second messenger that has been implicated in a wide range of cellular processes. Our earlier studies showed that c-di-AMP regulates central metabolism in Listeria monocytogenes by inhibiting its pyruvate carboxylase (LmPC), a biotin-dependent enzyme with biotin carboxylase (BC) and carboxyltransferase (CT) activities. We report here structural, biochemical, and functional studies on the inhibition of Lactococcus lactis PC (LlPC) by c-di-AMP. The compound is bound at the dimer interface of the CT domain, at a site equivalent to that in LmPC, although it has a distinct binding mode in the LlPC complex. This binding site is not well conserved among PCs, and only a subset of these bacterial enzymes are sensitive to c-di-AMP. Conformational changes in the CT dimer induced by c-di-AMP binding may be the molecular mechanism for its inhibitory activity. Mutations of residues in the binding site can abolish c-di-AMP inhibition. In L. lactis, LlPC is required for efficient milk acidification through its essential role in aspartate biosynthesis. The aspartate pool in L. lactis is negatively regulated by c-di-AMP, and high aspartate levels can be restored by expression of a c-di-AMP-insensitive LlPC. LlPC has high intrinsic catalytic activity and is not sensitive to acetyl-CoA activation, in contrast to other PC enzymes.