Cyclization of fungal nonribosomal peptides by a terminal condensation-like domain.

Cyclization of linear peptidyl precursors produced by nonribosomal peptide synthetases (NRPSs) is an important step in the biosynthesis of bioactive cyclic peptides. Whereas bacterial NRPSs use thioesterase domains to perform the cyclization, fungal NRPSs have apparently evolved to use a different enzymatic route. In verified fungal NRPSs that produce macrocyclic peptides, each megasynthetase terminates with a condensation-like (C(T)) domain that may perform the macrocyclization reaction. To probe the role of such a C(T) domain, we reconstituted the activities of the Penicillium aethiopicum trimodular NPRS TqaA in Saccharomyces cerevisiae and in vitro. Together with the reconstituted bimodular NRPS AnaPS, we dissected the cyclization steps of TqaA in transforming the linear anthranilate-D-tryptophan-L-alanyl tripeptide into fumiquinazoline F. Extensive biochemical and mutational studies confirmed the essential role of the C(T) domain in catalyzing cyclization in a thiolation domain-dependent fashion. Our work provides evidence of a likely universal macrocyclization strategy used by fungal NRPSs.

Acute Esophageal Necrosis (Gurvits Syndrome): A Rare Complication of Diabetic Ketoacidosis in a Critically Ill Patient.

Acute esophageal necrosis (AEN) is a rare clinical diagnosis that primarily affects the distal third of the esophagus. AEN causes odynophagia, leading to decreased oral intake and food avoidance. AEN can arise in critically ill patients with multiple comorbidities and is an uncommon complication of diabetic ketoacidosis (DKA). We present a case of a young female with poorly controlled, insulin-dependent diabetes mellitus type 2 who developed odynophagia, small volume coffee-ground emesis, and inability to tolerate oral intake after resolution of DKA. She was found to have esophagitis with esophageal necrosis in the middle third of the esophagus on upper gastrointestinal endoscopy. She was subsequently treated with fluid resuscitation and gastric acid suppression and improved clinically with slow advancements in her diet. The location of her lesion in the more vascularized middle one-third of the esophagus and lack of significant blood pressure variations during her hospital stay make her case unique. Thus, AEN should be considered in the differential diagnosis for critically ill patients who present with vague symptoms such as odynophagia and gastrointestinal bleeding.

Interstitial Emphysema as a Rare Radiographic Presentation of Bronchial Dehiscence after Lung Transplant.

Airway complications after lung transplantation are a major cause of morbidity and mortality. Bronchial dehiscence presents within a month of lung transplantation and is typically diagnosed radiographically as a sentinel gas pocket at the anastomotic site and confirmed with bronchoscopy. A 66-year-old man with idiopathic pulmonary fibrosis who underwent a right lung transplantation 4 weeks prior developed chest pain with palpable crepitus over his right chest wall. A chest X-ray revealed subcutaneous emphysema and a small right-sided pneumothorax. Computed tomography (CT) of the thorax without contrast revealed a gas pocket at the anastomotic site in the mediastinum as well as interstitial emphysema around the proximal bronchi of the right lung that had worsened when compared to CT from 11 days prior. A review of prior CT demonstrated interstitial emphysema without evidence of a sentinel gas pocket. These findings suggest that interstitial emphysema was the initial radiographic manifestation of the bronchial anastomotic site dehiscence. Interstitial emphysema is typically self-limiting, but severe cases can lead to major complications. Interstitial emphysema outside of the immediate postoperative period should be recognized as a possible early radiographic sign of bronchial dehiscence in lung transplant patients with vigilant monitoring of potential complications and strong consideration for early bronchoscopic investigation.

Primary extranodal jejunal diffuse large B cell lymphoma as a diagnostic challenge for intractable emesis: a case report and review of literature.

Introduction: The gastrointestinal tract is the most common extranodal site for non-Hodgkin's lymphoma, with the most common being diffuse large B cell lymphoma. Unlike the stomach or the ileum, the jejunum is a rare site for primary extranodal lymphomas, given the scarcity of lymphoid tissue. Due to its location, inflammation in the jejunum may not be visualized on routine imaging or endoscopy, making jejunal lymphoma difficult to diagnose. Case Description: We present a case of a 90-year-old male with 1 week of intractable emesis, initially thought to be due to viral gastroenteritis. His symptoms never improved and he underwent serial CT imagings in addition to esophagogastroduodenoscopy. A stomach biopsy and a diagnostic paracentesis did not reveal any malignant cells, but a CT enterography revealed significant jejunal inflammation with obstruction. After a month of hospitalization, a jejunal biopsy was obtained, which showed proliferation of neoplastic B cells. He was ultimately diagnosed with primary jejunal diffuse large B cell lymphoma. Discussion: Chemotherapy and surgical resection are typically the definitive treatment for extranodal lymphoma. Clinicians, however, must carefully consider the patient's functional and nutritional statuses before offering such interventions. This case was a diagnostic challenge and demonstrated a rare GI malignancy's convoluted mimicking nature.