Amphotericin B Induced Anaphylactic Reaction and Electrolyte Imbalance: A Case Report

Amphotericin B, a polyene antifungal antibiotic derived from a strain of Streptomyces nodosus. It acts by binding to sterols in the cell membrane of susceptible fungi, with a resultant change in the permeability of the membrane. Amphotericin B can cause allergic reactions, electrolyte imbalance and severe side effects, such as chest discomfort accompanied by dyspnea, flushing, agitation, tachypnea, tachycardia, hypoxemia, hypotension, or hypertension, are likely to develop following the injection of Amphotericin B. Anaphylaxis, cardiac toxicity and respiratory failure have also been associated to different formulations of Amphotericin B as life-threatening acute events. This case report is on a 57-year-old male patient who was admitted with a condition of left diabetic foot with non-healing medial supra heel ulcer and fungal infection on the site of wound. The patient was given Amphotericin B in emulsion form due to the high priority of fungal infection and the need for antifungal medicine, which led to anaphylactic reaction and electrolyte imbalance, which were treated immediately and the same preparation was continued with a low infusion rate. When infusion is discontinued, antihistamines can assist to alleviate the symptoms. In this case, it is recommended that the patient's condition and clinical parameters should be closely followed after the medicine has been administered.

Comparative Transcriptome Analysis of Streptomyces nodosus Mutant With a High-Yield Amphotericin B

Antibiotics play an important role in human health. Most antibiotics are derived from microbial secondary metabolites. Amphotericin is a polyene macrolide antibiotic synthesized by Streptomyces nodosus. S. nodosus ZJB2016050 with high-yield amphotericin B (AmB) was obtained by traditional mutagenesis using S. nodosus ATCC14899 as the original strain. The differences in the characterization of the two strains were found in color, mycelium morphology, and AmB yield. Subsequent comparative transcriptome explained the yield differences between the two strains. Pathways including the carbohydrate metabolic pathway and the secondary product synthesis pathway were targeted. The upregulation of glucokinase, phosphoglycerate mutase, and pyruvate dehydrogenase accelerates the consumption of glucose and has great effects on the accumulation of precursors. One of the competitive secondary metabolites of the polyketone synthetase (PKS) II type sapromomycin analog synthesis gene cluster was downregulated, which competes for malonyl-CoA. Five PKS modules (except for the first module amphA) of the amphotericin synthetic gene cluster in the high-yielding strain were downregulated, which resulted in the total amphotericin A (AmA) and AmB of S. nodosus ZJB2016050 being less than that of the wild-type S. nodosus ATCC14899. Combined with gene differential expression in the pentose phosphate pathway and the reaction mechanism of the ER5 domain, the reason that S. nodosus ZJB2016050 preferred to synthesize AmB was probably related to intracellular reduction.

Engineered Biosynthesis of Disaccharide-Modified Polyene Macrolides

ABSTRACTRecent work has uncovered genes for two glycosyltransferases that are thought to catalyze mannosylation of mycosaminyl sugars of polyene macrolides. These two genes arenypYfromPseudonocardiasp. strain P1 andpegAfromActinoplanes caeruleus. Here we analyze these genes by heterologous expression in various strains ofStreptomyces nodosus, producer of amphotericins, and inStreptomyces albidoflavus, which produces candicidins. The NypY glycosyltransferase converted amphotericins A and B and 7-oxo-amphotericin B to disaccharide-modified formsin vivo. The enzyme did not act on amphotericin analogs lacking exocyclic carboxyl or mycosamine amino groups. Both NypY and PegA acted on candicidins. This work confirms the functions of these glycosyltransferases and provides insights into their acceptor substrate tolerance. Disaccharide-modified polyenes may have potential as less toxic antibiotics.