Antibiotics That Inhibit Cell Wall Synthesis
Structure of the bacterial cell wall, the metabolic pathway for the biosynthesis of cell wall, and various antibiotics affecting various stages of cell wall synthesis are presented. Mechanisms of action of the antibiotics and the mechanisms of resistance
- PDF / 3,284,950 Bytes
- 46 Pages / 439.37 x 666.14 pts Page_size
- 38 Downloads / 211 Views
Antibiotics That Inhibit Cell Wall Synthesis
Abstract Structure of the bacterial cell wall, the metabolic pathway for the biosynthesis of cell wall, and various antibiotics affecting various stages of cell wall synthesis are presented. Mechanisms of action of the antibiotics and the mechanisms of resistance development to the antibiotics are discussed. The antibiotics include fosfomycin, cycloserine, β-lactams, carbapenems, bacitracin, moenomycin, mersacidin, vancomycin, and teixobactin. β-lactamase and β-lactamase inhibitors are discussed in the context of antibiotic resistance.
3.1 3.1.1
Background Biochemistry Information Carbohydrates
An introduction to sugars and polysaccharides is necessary in order to understand the structure of the bacterial cell wall. Monosaccharides. Carbohydrates or saccharides, which have the general formula (CH2O)n where n > 3, can be considered as “carbon hydrates.” The basic unit of a carbohydrate is called a monosaccharide, which usually has 3, 4, 5, or 6 carbons, the most common being C6 monosaccharides (Fig. 3.1). Polysaccharides have many covalently linked monosaccharides and can have molecular weights of millions of daltons. Monosaccharides can be aldehydes or ketones and are called aldoses or ketoses respectively. Ketoses have one chiral center less than aldoses. For example, glucose and fructose are both hexoses. Glucose is an aldose with four chiral centers and so has 24 = 16 stereoisomers. Fructose is a ketose with three chiral centers and so has 23 = 8 stereoisomers. Only half of these sugars are natural: those that have the OH at C5 on the right in Fischer projection formula and are called D-sugars. Sugars also exist in ring form, which is formed by reaction of C5–OH with the carbonyl carbon to form a hemiacetal or hemiketal. By this reaction the carbonyl carbon is changed to a new chiral center (called anomeric carbon) and so two stereoisomers (called anomers) are formed for each sugar. These are called α (anomeric OH pointing down) and β (anomeric OH pointing up) anomers. One way of drawing the ring
© Springer International Publishing Switzerland 2016 M.K. Bhattacharjee, Chemistry of Antibiotics and Related Drugs, DOI 10.1007/978-3-319-40746-3_3
49
50
3
Antibiotics That Inhibit Cell Wall Synthesis
Fig. 3.1 Structures of fructose and glucose. The wavy bond indicates that the bond can be pointing up (α-D-glucose) or down (β-D-glucose)
Fig. 3.2 Modified sugars: Glucosamine, N-acetylglucosamine, and N-acetyl muramic acid
structure is the Haworth projection formula in which all six atoms (5 carbons and an oxygen) of the ring are shown in one plane. However, this is not the true structure of the rings. Each carbon is sp3 hybridized and so is tetrahedral. In order to maintain ~108° angle (for sp3) with least torsional strain, the sugars exist in chair like structures in which four atoms of the ring are in one plane while C1 and C4 are alternately above and below the plane of the ring. Substituents can be either equatorial (pointing along the plane of the ring) or ax
Data Loading...
