Bacterial infections structure

In general, penicillins exert thek biological effect, as do the other -lactams, by inhibiting the synthesis of essential structural components of the bacterial cell wall. These components are absent in mammalian cells so that inhibition of the synthesis of the bacterial cell wall stmcture occurs with Htde or no effect on mammalian cell metaboHsm. Additionally, penicillins tend to be kreversible inhibitors of bacterial cell-wall synthesis and are generally bactericidal at concentrations close to thek bacteriostatic levels. Consequently penicillins have become widely used for the treatment of bacterial infections and are regarded as one of the safest and most efficacious classes of antibiotics. 

The penicillins are a class of compound having the general structure (1). Because of their unique effectiveness in the treatment of bacterial infections in humans, these compounds have been investigated intensively from the chemical, microbiological and clinical points of view since about 1940. The early history of these developments (see especially B-80MI51100, B-49MI51100) contains the following pivotal studies ... 

Chemotherapy is the control and treatment of disease by synthetic drugs. Most of these are organic compounds, often of remarkably simple structure. Sulfanilamide is one example of an organic compound synthesized by chemists for the treatment of bacterial infections. 

Systemic therapy with a variety of (3-lactams, macro-lides and lincosamides (clindamycin) has been the cornerstone of skin infection therapy for many years [17]. However, topical antibiotics can play an important role in both treatment and prevention of many primary cutaneous bacterial infections commonly seen in the dermatological practice [18], Indeed, while systemic antimicrobials are needed in the complicated infections of skin and skin structure, the milder forms can be successfully treated with topical therapy alone [18], The topical agents used most often in the treatment of superficial cutaneous bacterial infections are tetracyclines, mupirocin, bacitracin, polymyxin B, and neomycin. 

Following with bacterial infections and anti-adhesion strategies,86 88 NMR based structural studies have been conducted on O-polysaccharide chains in these past few years,38 40,42,43 in order to elucidate the molecular basis and the role of the lipopolysaccharides in these pathologies. 

The cell nucleus is another important source of druggable targets. Surprisingly, the nucleus is not as important to the survival of an individual cell as are many of the cytoplasmic organelles. A cell can live without its nucleus, it just cannot reproduce. (Mature adult human red blood cells, for example, do not have nuclei.) On the other hand, a cell cannot live without its mitochondria. Therefore, the cell nucleus is an important structure to target when designing drugs for diseases in which one wishes to stop cellular reproduction (e.g., cancer, viral or bacterial infections). 

The most common oral condition and dental emergency is dental caries, which is a destructive disease of the hard tissues of the teeth due to bacterial infection with Streptococcus mutans and other bacteria. It is characterized by destruction of enamel and dentine. Dental decay presents as opaque white areas of enamel with grey undertones and in more advanced cases, brownish discoloured cavitations. Dental caries is initially asymptomatic and pain does not occur until the decay impinges on the pulp, and an inflammation develops. Treatment of caries involves removal of the softened and infected hard tissues, sealing of exposed dentines and restoration of the lost tooth structure with porcelain, silver, amalgam, composite plastic, gold etc. 

Figure 8.1. Biofilms are microbial communities that are made up of several species and often possess a distinct spatial structure. It has been found that living in a biofilm can offer significant protection to individuals, with sterilisation agents and even antibiotics being less potent against individuals if they are found in a biofilm. This is significant because it has been estimated that nearly three quarters of bacterial infections involve microbes that live in biofilm communities. Although there is a growing literature on the effects of NPs on biofilms, there is currently little knowledge of the production and metabolism of NPs in biofilms.

Because peptidoglycans are unique to bacterial cell walls, with no known homologous structures in mammals, the enzymes responsible for their synthesis are ideal targets for antibiotic action. Antibiotics that hit specific bacterial targets are sometimes called magic bullets. Penicillin and its many synthetic analogs have been used to treat bacterial infections since these drugs came into wide application in World War II. 

Sulfa drugs have a close structural resemblance to PABA. When taken by a person suffering from a bacterial infection, a sulfa drug is transformed by the body to the compound sulfanilamide, which attaches to the bacterial receptor sites designed for PABA, as shown in Figure 14.7, thereby preventing the synthesis of folic acid. Without folic acid, the bacteria soon die. The patient, however, because he or she receives folic acid from the diet, lives on. 

The development of antibacterial chemotherapy during the past 75 years has spearheaded the successful use of today s drugs to combat bacterial infections. Studies in (3-lactam chemistry were stimulated when (3-lactam ring, the four membered heterocycle, was recognized as a key structural feature as well as a key therapeutic feature of the bicyclic (3-lactam antibiotics such as penicillins, cephalosporins, and other classical antibiotics. The last two decades have registered the discovery of several nonclassical bicyclic (3-lactam antibiotics, e.g., thienamycin and carba-penems of natural origin like olivanic acids, carpetimycin, pluracidomycin, and aspareomycins. 

Artificial antigens containing immunodeterminant structures of O-antigens represent potent non-toxic immunogens that induce high-titer antisera which may be used for diagnostic purposes and which may have the capacity to protect specifically against bacterial infections. 

As indicated in Chapter 33, metronidazole has bactericidal effects and is used in certain gram-negative bacterial infections. This drug may be administered orally or intravenously. Other agents have also been developed that are structurally and functionally similar to metronidazole. Tinidazole (Tindamax), for example, can be used in cases where metronidazole is not tolerated or is ineffective.24... 

The importance of these structures is clear by observing the numerous biomedical applications7711 that have been suggested for such compounds including inhibition of viral and bacterial infections, tumor eradication by stimulating the immune response, preventing toxin binding, and many others. Selected examples have been chosen to illustrate these potentialities. 

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