Targeting cell wall synthesis and assembly in microbes: similarities and contrasts between bacteria and fungi.
icrobial cells possess a form of exoskeleton called the cell wall that protects the organism from osmotic pressure and environmental insults. Synthesis of the various building blocks that make up the cell wall occurs in the cytoplasm, and thus microbial cells face specific biochemical and biophysical problems related to the polymerization, transport, and assembly of building blocks into the final wall structure at an extra-cellular site. Cell walls must also be metabolically and structurally pliable in order to allow for processes such as repair, secretion, DNA exchange, and cell division. In some cases, bacteria and fungi use similar mechanisms, to accomplish synthesis and assembly, while in other cases each used divergent strategies to accomplish specific functions. This review will summarize recent advances in our understanding of fungal and bacterial cell wall synthesis and assembly. We will compare specific pathways used by both fungi and bacteria, paying particular attention to identifying those areas where what is known in one system may point to approaches to solving unanswered questions in the other. The structure, chemical properties, and mechanism of action of select natural and synthetic products which inhibit synthesis or assembly of cells walls will be discussed in terms of similarities in the structures, and/or steps in the synthetic process targeted. In addition, new targets in the pathways will be presented along with recent approaches to the discovery and design of novel inhibitors.
Goldman
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Intercardia Research Laboratories, 8 Cedar Brook Drive, Cranbury, NJ 08512, USA. rgoldman@irl.intercardia.com
Branstrom
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D000595:Amino Acid Sequence; D001419:Bacteria / Q000378:metabolism*; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism*; D002686:Chitin / Q000096:biosynthesis; D004286:Dolichols / Q000378:metabolism; D005658:Fungi / Q000737:chemistry / Q000378:metabolism*; D005936:Glucans / Q000096:biosynthesis; D006031:Glycosylation; D008070:Lipopolysaccharides / Q000096:biosynthesis; D008351:Mannans / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000096:biosynthesis
D004286:Dolichols; D005936:Glucans; D008070:Lipopolysaccharides; D008351:Mannans; D010457:Peptidoglycan; D002686:Chitin