Safely Doing Less Antibiotics: Evidence to Guide Duration and Route of Administration in Common Pediatric Infections.

The growing evidence detailing the harmful effects of exposure to antibiotics has driven an urgency to evaluate recommendations in common pediatric infections regarding antibiotic course duration and route of administration. The past decade has produced strong evidence in support of many patients with uncomplicated common pediatric infections receiving shortened antibiotic durations and early conversion from intravenous to oral antibiotics. In this review, we offer guidance to providers in selection of duration and route of administration in a subset of common pediatric infections, including community-acquired pneumonia, osteomyelitis, and infections of the head and neck. [Pediatr Ann. 2024;53(6):e229-e233.].

Phytochelatin synthase is required for tolerating metal toxicity in a basidiomycete yeast and is a conserved factor involved in metal homeostasis in fungi.

BACKGROUND: Phytochelatin synthase (PCS) is an enzyme that catalyzes the biosynthesis of phytochelatin from glutathione. Phytochelatins protect cells against the toxic effects of non-essential heavy metals, such as cadmium, and hence growth is restricted in the presence of these metals in mutants in PCS-encoding genes. PCS genes from fungi have been characterized in only two species in the Ascomycota, and these genes are considered sparsely distributed in the fungal kingdom. RESULTS: A gene encoding a putative PCS was identified in Sporobolomyces sp. strain IAM 13481, a fungus that is a member of the Pucciniomycotina subphylum of the Basidiomycota. The function of this PCS1 gene was assessed by heterologous expression in the Ascomycota yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, and by mutating the gene in Sporobolomyces. The gene is required for tolerance to toxic concentrations of non-essential cadmium as well as the essential metal copper. Pcs1 homologs in fungi and other eukaryotes have putative targeting sequences for mitochondrial localization: the S. pombe homolog was fused to green fluorescent protein and it co-localized with a mitochondrial dye. Evaluation of the presence or absence of PCS and PCS-like homologs in the genome sequences of fungi indicates that they have a wide distribution, and the absence in most Ascomycota and Basidiomycota (the Dikarya) species can be explained by a small number of gene losses. CONCLUSIONS: The ecology of the species within the fungi carrying putative PCS genes, the phenotypes of phytochelatin synthase mutants in two major fungal lineages, and the presence of homologs in many non-Dikarya lineages parallel what is seen in the plant and animal kingdoms. That is, PCS is a protein present early during the evolution of the fungi and whose role is not solely dedicated to combating toxic concentrations of non-essential metals.