The biosynthesis of caprazamycins and related liponucleoside antibiotics: new insights

Abstract The first step in the membrane cycle of reactions during peptidoglycan biosynthesis is the transfer of phospho-MurNAc-pentapeptide from UDP-MurNAc-pentapeptide to undecaprenyl phosphate, catalyzed by the integral membrane protein MraY translocase. Different MraY inhibitors are known and can be subdivided into classes depending on their structural composition. Caprazamycins belong to the liponucleoside class of antibiotics isolated from Streptomyces sp. MK730-62F2. They possess activity in vitro against Gram-positive bacteria, in particular against the genus Mycobacterium including Mycobacterium intracellulare, Mycobacterium avium and Mycobacterium tuberculosis. Caprazamycins and the structurally related liposidomycins and A-90289 share a unique composition of moieties. Their complex structure is derived from 5′-(β-O-aminoribosyl)-glycyluridine and comprises a unique N,N′-dimethyldiazepanone ring. Recently, the corresponding biosynthetic gene clusters of caprazamycins, liposidomycins and A-90289 have been discovered and will be compared in this review. New information is also emerging regarding the biosynthesis of liponucleoside antibiotics obtained by gene disruption experiments and biochemical investigations.</jats:p

Safety and working conditions in international merchant shipping A study of fatal occupational accidents and a survey of world-wide fatality statistics of merchant seafarers

Includes bibliographical referencesAvailable from British Library Document Supply Centre- DSC:DX219343 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Mechanism of action of the uridyl peptide antibiotics: an unexpected link to a protein-protein interaction site in translocase MraY

The pacidamycin and muraymycin uridyl peptide antibiotics show some structural resemblance to an Arg-Trp-x-x-Trp sequence motif for protein-protein interaction between bacteriophage phi X174 protein E and E. coli translocase MraY. Members of the UPA class, and a synthetic uridine-peptide analogue, were found to show reduced levels of inhibition to F288L or E287A mutant MraY enzymes, implying that the UPAs interact at this extracellular site as part of the enzyme inhibition mechanism.</p

A Host-Directed Approach to the Detection of Infection in Hard-to-Heal Wounds

Wound infection is traditionally defined primarily by visual clinical signs, and secondarily by microbiological analysis of wound samples. However, these approaches have serious limitations in determining wound infection status, particularly in early phases or complex, chronic, hard-to-heal wounds. Early or predictive patient-derived biomarkers of wound infection would enable more timely and appropriate intervention. The observation that immune activation is one of the earliest responses to pathogen activity suggests that immune markers may indicate wound infection earlier and more reliably than by investigating potential pathogens themselves. One of the earliest immune responses is that of the innate immune cells (neutrophils) that are recruited to sites of infection by signals associated with cell damage. During acute infection, the neutrophils produce oxygen radicals and enzymes that either directly or indirectly destroy invading pathogens. These granular enzymes vary with cell type but include elastase, myeloperoxidase, lysozyme, and cathepsin G. Various clinical studies have demonstrated that collectively, these enzymes, are sensitive and reliable markers of both early-onset phases and established infections. The detection of innate immune cell enzymes in hard-to-heal wounds at point of care offers a new, simple, and effective approach to determining wound infection status and may offer significant advantages over uncertainties associated with clinical judgement, and the questionable value of wound microbiology. Additionally, by facilitating the detection of early wound infection, prompt, local wound hygiene interventions will likely enhance infection resolution and wound healing, reduce the requirement for systemic antibiotic therapy, and support antimicrobial stewardship initiatives in wound care