Blood proteins, antibacterial

Genes Specifying Antibacterial Protein Structure. Adult flies and larvae of Drosophila and Ceratitis do not normally contain in their blood proteins that specifically kill bacteria. However, when animals are inoculated with Enterobacter cloacae, potent antibacterial activity appears in the blood (11,12,17,18). Antibacterial activity is detected in the blood of adult Drosophila melanogaster flies within two hours after inoculation, and is still detectable sixty days later (11). Investigation of this activity by isoelectric focusing reveals several blood proteins with antibacterial activity... 

Although the determination of the tissue levels gives important information about distribution of the sulfonamides in various organs (15), it furnishes no indication as to the local active concentration of the antibacterial. According to modem views, sulfonamides are bound reversibly to blood proteins, mostly the albumins. The degree of protein binding varies considerably among various... 

One mechanism by which fever has an antibacterial effect is that it decreases the blood concentration of iron, which is necessary for bacterial proliferation (Chapter 17). However, iron is also necessary for the proliferation of immune cells in the lymph nodes and in the bone marrow (for formation of the iron-containing proteins, haemoglobin and mitochondrial proteins). This leads to competition for iron in the... 

Haematological measurements (e.g. white cell count, C-reactive protein) may not reveal the necessary changes of response to antibiotics, so repeat blood cultures are necessary as there is a theoretical risk that inadequate antibacterial therapy will promote the development of drug-resistant strains of bacteria. 

Fly blood does not normally contain substances that kill bacteria, but flies inoculated with bacteria rapidly accumulate antibacterial proteins (ABs) in their blood. Wild type Drosophila have at least three different antibacterial proteins based on isoelectric points. Genetic variants identify structural genes for these antibacterial proteins. A DNA sequence that can encode a conserved portion of moth and fleshfly antibacterial proteins has been used to synthesize a complementary oligonucleotide probe. This probe recognizes a messenger RNA that appears in the fat body of Drosophila and Medflies only after they have been inoculated with bacteria. Bacteria-sensitive lethal mutations were induced to identify genes necessary for flies to survive a bacterial infection. 

Although historically most useful antibiotics have come from spore forming microorganisms, marine organisms have yielded the candidate antitumor peptide didemnin B [77327-50-0] (2) and cytostatic peptides such as the patellamides (3). Many of the marine peptides have little or no antimicrobial activity. Antibacterial peptides called magainins are found in frog skin (4) and antibacterial proteins called defensins are found in mammalian white blood cells (5). The commercially important insecticidal proteins from Bacillus thuringensis (6) are not discussed herein nor are the numerous peptide siderophores (7,8), which, except for the albomycins (9), are usually not antimicrobial. 

A) Oral bioavailability is affected by first-pass hepatic metabolism Only third-generation cephalosporins cross the blood-brain barrier Procaine penicillin G is the most commonly used intravenous form of the antibiotic Renal tubular reabsorption of beta-lactams is inhibited by probenecid Nafcillin and ceftriaxone are eliminated mainly via biliary secretion The mechanism of antibacterial action of cephalosporins involves (A) Inhibition of the synthesis of precursors of peptidoglycans Interference with the synthesis of ergosterol Inhibition of transpeptidation reactions Inhibition of beta-lactamases Binding to cytoplasmic receptor proteins... 

This peroxidase, present in milk, saliva, and tears, is involved in the bacterial defense through the oxidation of thiocyanate ions to the antibacterial species hypothiocyanate OSCN and other higher oxyacids. Thiocyanate, the physiological substrate of LPO, is present in secreted fluids in much higher concentrations than in blood plasma or in the extracellular space of tissues. LPO is a glycoprotein with a molecular weight of 78,000 Da and has a high content of carbohydrates (10%). Despite the absence of an X-ray structure for LPO, physico-chemical studies have shown that the bovine milk LPO-heme is a l,5-bis(hydroxymethyl) derivative of heme b, linked to the protein by esterification with Glu-275 and Asp-125 as in MPO. ... 

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