Antibiotics bacterial selectivity

Widespread use of (3-lactam antibiotics exerts selective pressure on bacteria and permits the proliferation of resistant organisms. A comparison of current antibiograms with those from previous decades shows an alarming increase in bacterial resistance to (3-lactam antibiotics. 

MJ Mahan, JW Tobias, JM Slouch, PC Hanna, RJ Collier, JJ Mekalanos. Antibiotic-based selection for bacterial genes that are specifically induced during infection of a host. Proc Natl Acad Sci (USA) 92 669-673, 1995. 

The use of steroids in ocular infections requires caution to avoid interfering with reparative processes. If the appropriate antibiotic is selected and if the course of therapy is relatively short, steroids can help to reduce inflammation and prevent possible scarring. In general, however, steroids should be avoided in cases of routine bacterial infections of the eyelids and conjunctiva when no scarring is anticipated, because steroids provide relatively little benefit in the healing process. 

D. Treatment of bacterial infections Antibiotics that selectively affect bacterial function and have minimal side effects in humans are usually selected to treat bacterial infections. Rifampicin, which inhibits the initiation of prokaryotic RNA synthesis, is used to treat tuberculosis. Streptomycin, tetracycline, chloramphenicol, and erythromycin inhibit protein synthesis on prokaiyotic ribosomes and are used for many infections. Chloramphenicol affects mitochondrial ribosomes and must be used with caution. 

A meta-analysis of 32 trials reported no difference in effect (cure rates) after short (<7 days) and usual durations (>7 days) of antibiotic therapy in children. The authors suggest that 5 days of therapy is effective in acute uncomplicated otitis media. The advantages of short-term therapy are an increased hkelihood the patient wiU adhere to the full course of treatment and decreased bacterial selective pressure for both the individual and the community. The disadvantages are that the data are not well estabhshed for comphcated or recurrent acute otitis media, and there are inadequate data to support short treatment courses in children younger than 2 years of age. ... 

The bacterial selectivity of antibiotics pertains to an interference with prokaryotic protein synthesis as distinguished from eukaryotic protein synthesis (Muench, in Devlin, 1986, pp. 936,937). As has been indicated, however, some of the antibiotics are too toxic for clinical use, although useful in studying protein synthesis. 

Figure 27.28 shows a few of the important antibiotics that act by inhibiting translation. Many translation-inhibiting antibiotics work selectively on prokaryotic organisms because the process of translation is sufficiently different in them than it is in humans. Thus, these compounds can be used to treat bacterial infections with minimal side effects to humans. 

Figure 7.1 Selective toxicity of antibiotics. Bacterial cells differ from normal human cells in that they have cell walls, structurally-different ribosomes, and unique metabolic pathways. Antibiotics are designed to exploit these differences so that bacteria, but not human cells, are damaged.

Herrero, M., de Lorenzo, V, and Timmis, K.N. (1990) Transposon vectors containing non-antibiotic resistance selection markers for cloning and stable chromosomal insertion of foreign genes in gram-negative bacteria. / Bacterial., 172 (11), 6557—6567. 

Biotechnological products of high thermal resistance, with a thermal inactivation rate that is low and critical moisture content reaches several percent. So, these are thermo- and xerostable substances. The assumed boundary values are temperature, about 150°C and moisture content, 5%-7% by weight. This group contains the products of microbiological synthesis and spores (e.g., amino acids, antibiotics, and selected bacterial strains). 

The antibacterial effectiveness of penicillins cephalospotins and other P-lactam antibiotics depends upon selective acylation and consequentiy, iaactivation, of transpeptidases involved ia bacterial ceU wall synthesis. This acylating ability is a result of the reactivity of the P-lactam ring (1). Bacteria that are resistant to P-lactam antibiotics often produce enzymes called P-lactamases that inactivate the antibiotics by cataly2ing the hydrolytic opening of the P-lactam ring to give products (2) devoid of antibacterial activity. 

This insertion is accomplished by an enzyme called transpeptidase. -Lactam antibiotics function as substrates for the transpeptidase, thereby establishing selective inhibition of bacterial cell wall synthesis. The structural similarity between -lactam antibiotics and the alanylalanine unit is remarkable as can be seen in Figure 6.8. 

The phenomenon of bacterial resistance to antibiotics was already known by the pioneers of the era of antibiotics, like Paul Ehrlich, who coined the term selective toxicity as the basic principle of antimicrobial therapeutics, as well as Gerhard Domagk, the inventor of the sulfonamide drugs, and Sir Alexander Fleming, the discoverer of the penicillins. When penicillin G was introduced into clinical practice in 1944, as many as 5% of the isolates of Staphylococcus aureus were resistant to penicillin, while 5 years later the percentage was 50%. 

Furthermore, if the antibiotic passes membranes through a specific port of entry, its mutational loss leads to resistance. The lack of the outer membrane protein OprD in P. aeruginosa causes resistance to the (3-lactam antibiotic imipenem. Fosfomycin passes the cytoplasmic membrane via an L-a-glycerol phosphate permease. This transport system is not essential for bacterial growth and therefore mutants with a reduced expression are frequently selected under therapy. 

Certain of these peptoid antibiotics are also selective for bacterial, rather than mammalian, cells. The selectivity of these peptoids has been measured in terms of their capacity to cause hemolysis of human erythrocytes at or near their MIC (Tab. 1.3). Interestingly, the amount of hemolysis induced by these peptoids correlates well with their hydrophobicity as there is an increasing extent of hemolysis as molecular hydrophobicity increases. These results suggest that highly hydro-phobic compounds of this class are poorly selective antibiotics. The most active antibacterial peptoids, T2-15 and T3-12, have quite low hemolytic activity near their MICs. Although highly antibacterial in vitro, T3-17 is also very hemolytic at its MIC value. 

Of the fonr possible optical isomers of chloramphenicol, only the o-threo form is active. This antibiotic selectively inhibits protein synthesis in bacterial ribosomes by binding to the 50S subunit in the region of the A site involving the 23 S rRNA. The normal binding of the aminoacyl-tRNA in the A site is affected by chloramphenicol in such a... 

---