Chemistry of antibiotics from Atlantic Actinomycete and Bacillus bacteria
The emergence of drug-resistant pathogens requires the use of innovative therapeutic agents. Hospital-acquired (nosocomial) infections represent major health and economic burdens for patients and health care professionals. In the United States over 1 million nosocomial infections are caused by drug-resistant bacteria anually, with associated expenditures ranging from $4 to $30 billion. Methicillin-resistant Staphylococcus aureus (MRSA) commonly shows reduced susceptibility to β-lactam, peptide, macrolide, aminoglycoside, tetracycline, and lincosamide classes of antibiotics. The emergence of vancomycin-resistant enterococci (VRE) is even more alarming since glycopeptide antibiotics were once considered the drugs of last resort. Moreover, community-acquired MRSA infections are spreading out of the hospital and are now found among individuals with no known health risks.^ Traditional antimicrobial chemotherapy has relied upon the production of antibiotics from terrestrial microorganisms. However, oversampling from these sources has significantly decreased the frequency of isolating new compounds. An alternative approach to combating pathogens such as MRSA and VRE is the investigation of marine environments for autochthonous microorganisms that produce structurally unique antibiotics with new mechanisms of action.^ Gram-positive marine bacteria are an underexplored resource for such chemistry. These organisms possess novel biosynthetic genes and can provide molecules with unprecedented structure and biological activity. The goal of the following work was to screen, isolate, and characterize antibiotics produced by Actinomycete and Bacillus sp. bacteria isolated from the North Atlantic Ocean and the Caribbean Sea. In total 65 strains of actinomycetes (45 Streptomyces sp., 20 Micromonospora sp.) and 66 strains of Bacillus sp. were screened using microscale bioassay-guided fractionation. The active molecules in crude extract “hits” were purified by chromatographic methods, and previously known metabolites were dereplicated using the available literature. Chemical structures of new compounds were elucidated through a combination of spectroscopic and chemical methods including nuclear magnetic resonance (NMR), mass spectrometry (MS), circular dichroism (CD), infared (IR), and ultraviolet (UV) spectroscopy. When appropriate, semi-synthesis derivatives were prepared and structure activity studies were conducted against clinically-isolated pathogens. ^
Chemistry, Analytical|Chemistry, Organic|Chemistry, Pharmaceutical
Aaron Martin Socha,
"Chemistry of antibiotics from Atlantic Actinomycete and Bacillus bacteria"
Dissertations and Master's Theses (Campus Access).