Covalent Irreversible Inhibitors of Tetracycline Destructases.

Next-generation tetracycline antibiotics are threatened by an emerging resistance mechanism ─ enzymatic inactivation. The relevant enzymes ─ tetracycline destructases (TDases) ─ are structural homologues of class A flavin monooxygenase (FMO) that oxidize tetracycline antibiotics, leading to various inactive degradation products. Small molecule inhibitors of antibiotic-inactivating enzymes are critical clinical therapeutics used to manage bacterial resistance with combination therapy.

The tetracycline resistome is shaped by selection for specific resistance mechanisms by each antibiotic generation.

The history of clinical resistance to tetracycline antibiotics is characterized by cycles whereby the deployment of a new generation of drug molecules is quickly followed by the discovery of a new mechanism of resistance. This suggests mechanism-specific selection by each tetracycline generation; however, the evolutionary dynamics of this remain unclear. Here, we evaluate 24 recombinant Escherichia coli strains expressing tetracycline resistance genes from each mechanism (efflux pumps, ribosomal protection proteins, and enzymatic inactivation) in the context of each tetracycline generation.

C10-Benzoate Esters of Anhydrotetracycline Inhibit Tetracycline Destructases and Recover Tetracycline Antibacterial Activity.

Tetracyclines (TCs) are an important class of antibiotics threatened by enzymatic inactivation. These tetracycline-inactivating enzymes, also known as tetracycline destructases (TDases), are a subfamily of class A flavin monooxygenases (FMOs) that catalyze hydroxyl group transfer and oxygen insertion (Baeyer-Villiger type) reactions on TC substrate scaffolds. Semisynthetic modification of TCs (e.

Comparison of sampling and culture methods for the recovery of yeast from hospital surfaces.

Objective: To compare the recovery of yeast from hospital surfaces from two different collection methods: Eswab moistened with molecular water, and premoistened stick-mounted sponge.

Design: Comparison of collection methods for the recovery of yeast in the hospital environment.

Setting: This study took place at intensive care units of a large academic medical center.

Sequence-structure-function characterization of the emerging tetracycline destructase family of antibiotic resistance enzymes.

Tetracycline destructases (TDases) are flavin monooxygenases which can confer resistance to all generations of tetracycline antibiotics. The recent increase in the number and diversity of reported TDase sequences enables a deep investigation of the TDase sequence-structure-function landscape. Here, we evaluate the sequence determinants of TDase function through two complementary approaches: (1) constructing profile hidden Markov models to predict new TDases, and (2) using multiple sequence alignments to identify conserved positions important to protein function.

Novel mitochondrial complex I-inhibiting peptides restrain NADH dehydrogenase activity.

The emergence of drug-resistant fungal pathogens is becoming increasingly serious due to overuse of antifungals. Antimicrobial peptides have potent activity against a broad spectrum of pathogens, including fungi, and are considered a potential new class of antifungals. In this study, we examined the activities of the newly designed peptides P-113Du and P-113Tri, together with their parental peptide P-113, against the human fungal pathogen Candida albicans.

The Transcription Factor Sfp1 Regulates the Oxidative Stress Response in .

is a commensal that inhabits the skin and mucous membranes of humans. Because of the increasing immunocompromised population and the limited classes of antifungal drugs available, has emerged as an important opportunistic pathogen with high mortality rates. During infection and therapy, .

The Antimicrobial Peptides P-113Du and P-113Tri Function against Candida albicans.

Two antimicrobial P-113 peptide derivatives, P-113Du and P-113Tri, were investigated in this study. Notably, P-113Du and P-113Tri contained significant fractions of α-helix conformation and were less sensitive to high salt and low pH than P-113. Moreover, compared to P-113, these peptides exhibited increased antifungal activity against planktonic cells, biofilm cells, and clinical isolates of Candida albicans and non-albicans Candida spp.