ABSTRACT
Drug-resistant bacteria continue to make many existing antibiotic classes ineffective. In order to avoid a future epidemic from drug-resistant bacterial infections, new antibiotics with new modes of action are needed. In an antibiotic screening program for new drug leads with new modes of action using antisense Staphylococcus aureus Fitness Test screening, we discovered a new tetramic acid, methiosetin, from a tropical sooty mold, Capnodium sp. The fungus also produced epicorazine A, a known antibiotic. The structure and relative configuration of methiosetin was elucidated by 2D NMR and ESIMS techniques. Methiosetin and epicorazine A showed weak to modest antibacterial activity against S. aureus and Haemophilus influenzae. The isolation, structure elucidation, and antibacterial activity of both compounds are described.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Ascomycota/chemistry , Pyrrolidinones/isolation & purification , Pyrrolidinones/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Guatemala , Haemophilus influenzae/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Molecular Structure , Piperazines/isolation & purification , Piperazines/pharmacology , Pyrrolidinones/chemistryABSTRACT
Several protocols for bacterial isolation and techniques for aerobic plate counting rely on the use of a spiral plater to deposit concentration gradients of microbial suspensions onto a circular agar plate to isolate colony growth. The advantage of applying a gradient of concentrations across the agar surface is that the original microbiological sample can be applied at a single concentration rather than as multiple serial dilutions. The spiral plater gradually dilutes the sample across a compact area and therefore saves time preparing dilutions and multiple agar plates. Commercial spiral platers are not automated and require manual sample loading. Dispensing of the sample volume and rate of gradients are often very limited in range. Furthermore, the spiral sample application cannot be used with rectangular microplates. Another limitation of commercial spiral platers is that they are useful only for dilute, filtered suspensions and cannot plate suspensions of coarse organic particles therefore precluding the use of many kinds of microorganism-containing substrata. An automated agar plate spreader capable of processing 99 rectangular microplates in unattended mode is described. This novel instrument is capable of dispensing discrete volumes of sample in a linear pattern. It can be programmed to dispense a sample suspense at a uniform application rate or across a decreasing concentration gradient.
