Biomedical Engineering Reference
In-Depth Information
CH
3
OCH
2
CH
2
OCH
2
CH
3
NH
CH
3
N
CH
3
CH
3
CH
3
O
9
HO
HO
HO
CH
3
CH
3
FIGURE 25.16
C
7
-C
12
fragments of dirithromycin and azithromycin.
Erythromycin is very active against Gram-positive bacteria. Oleandomycin has a similar spec-
trum, but the MIC are generally higher.
Spiramycin and leucomycin are macrolides with a more limited use. Spiramycin was discovered
in
S. ambofaciens
(1955). Besides the main component I, it contains some components II (max.
15%) and III (max. 10%).
Another active macrolide is tylosin. Its application is restricted to veterinary medicine.
25.5.2.3 Lincomycin, Clindamycin
Lincomycin is also a basic antibiotic isolated in 1962 from
Streptomyces lincolnensis
. The basic
group is in the proline part of the molecule and the sugar moiety contains a methylmercapto group.
In 1967, it was shown that replacement of a hydroxy group by chlorine, with inversion of coni gura-
tion, resulted in a product clindamycin, with improved absorption and higher serum levels. Both
antibiotics are active against Gram-positive bacteria, with a spectrum similar to that of erythromy-
cin. Side effects are diarrhea and occasionally serious pseudomembranous colitis, which is caused
by an overgrowth of clindamycin-resistant strains of
Clostridium difi cile
(Figure 25.17).
25.5.2.4 Fusidic Acid
Fusidic acid (Figure 25.6) was isolated from
Fusidium coccineum
in 1962. It has a unique steroid
type (fusidane) structure. Cephalosporin P
1
has a similar structure. Fusidic acid is active against
Gram-positive bacteria and Gram-negative cocci. Resistant strains rapidly emerge. Because of this
observation, its use is limited.
25.6 CELL WALLS OF BACTERIA
Most prokaryotic cells are surrounded by a cell wall that is responsible for their shape and allows
bacteria to live in a hypotonic environment without bursting. In 1884, C. Gram discovered that
some bacteria retained crystal violet-iodine complex after washing with alcohol (Gram-positive)
and others did not (Gram-negative).
Gram-positive cells are surrounded by a cytoplasmic membrane and a thick cell wall consisting of
peptidoglycan to which are linked polyol phosphate polymers called teichoic acids. Gram-negative
bacteria have a much thinner cell wall consisting of peptidoglycan and associated proteins, and this
cell wall is surrounded by an outer membrane comprising of lipid, lipopolysaccharide, and protein.
The osmotic pressure in the cytoplasm of Gram-positive bacteria (±20 atm) is higher than that of in
Gram-negative (±5 atm).
Peptidoglycan is an alternating polymer of
N
-acetylglucosamine (NAG) and
N
-acetylmuramic
acid (NAM), which are cross-linked by a short peptide bridge, and which is 200-250 Å thick in
Gram-positive bacteria. Peptidoglycan forms an enormous bag shaped molecule, also called “murein
sacculus” (Latin murus: wall), which surrounds the entire cell.
NAM is the 3-
O
-d-lactylether of
N
-acetylglucosamine. NAG and NAM are linked by
b(1-4) glycosidic bonds and form a linear structure as in cellulose (glucose units) and in chitin
