Resistance of bacteria

Lactamases (EC 3.5.2.6) inactivate /3-lactam antibiotics by hydrolyzing the amide bond (Fig. 5.1, Pathway b). These enzymes are the most important ones in the bacterial defense against /3-lactam antibiotics [15]. On the basis of catalytic mechanism, /3-lactamases can be subdivided into two major groups, namely Zn2+-containing metalloproteins (class B), and active-serine enzymes, which are subdivided into classes A, C, and D based on their amino acid sequences (see Chapt. 2). The metallo-enzymes are produced by only a relatively small number of pathogenic strains, but represent a potential threat for the future. Indeed, they are able to hydrolyze efficiently carbape-nems, which generally escape the activity of the more common serine-/3-lac-tamases [16] [17]. At present, however, most of the resistance of bacteria to /3-lactam antibiotics is due to the activity of serine-/3-lactamases. These enzymes hydrolyze the /3-lactam moiety via an acyl-enzyme intermediate similar to that formed by transpeptidases. The difference in the catalytic pathways of the two enzymes is merely quantitative (Fig. 5.1, Pathways a and b). 

Kolwzan B., T. Traczewska, and M. Pawlaczyk-Szipilowa (1991). Examination of resistance of bacteria isolated from drinking water to antibacterial agents. Environmental Protection Engineering 17 53-60. 

Microbes acquire iron by utilizing very specific, low molecular weight iron chelators called siderophores. The resistance of bacteria to previously effective antibiotics can be circumvented in part by covalent coupling of antibiotics to siderophores. Some synthetic siderophores have been found to possess significant antibacterial activity themselves. They have also been found to have considerable potential as nontoxic, organ selective MRI contrast agents (27). 

Due to the increasing resistance of bacteria to /1-lactams, new syntheses and novel structural variants are continuously being sought562,563. Some recent examples are described below. 

As a consequence of the increased resistance of bacteria to classical /3-lactam antibiotics, several strategies devoted to the synthesis of new bi- and polycyclic /3-lactam derivatives have been developed, giving rise to a large number of compounds featuring enhanced antibacterial activity or better resistance toward /3-lactamases. It is the aim of this section to extend previous accounts on this subject in CHEC(1984) and CHEC-II(1996) and to summarize several recent methodologies concerning the preparation of these fused heterocycles. 

By the methods presented for the combinatorial biosynthesis of polyketides, a multitude of modified and artificial polyketide substances should be available. New antibiotics, potentially with fewer side effects and consequently broader applicability, are desperately needed in the light of increasing resistance of bacteria towards established medications. 

In medicine, we do a similar thing if we want to control microbial diseases. To overcome or to prevent resistance of bacteria toward a particular antibiotic, very often mixtures of structurally different antibiotics are applied, whose molecular targets often differ. If only one antibiotic were given to all patients, the development of resistance would be much favored. 

The /3-lactam antibiotics may be susceptible to attack by three bacterial enzymes acylases, esterases and /3-lactamases. However, only the /8-lactamases play a significant role in the resistance of bacteria to penicillins and cephalosporins. 

Chomarat M. Resistance of bacteria in urinary tract infections. Int J Antimicrob Agents 2000 16(4) 483-7. 

Although the phenomenon of multidrug resistance of bacteria was observed more than fifty years ago, it took 20 years until the first drug transporter, P-glycoprotein, was discovered as the responsible cellular factor for the outward transport of xenobiotics of different chemical structure. Another ten years later, experimental results on different tumor cell lines indicated that P-glycoprotein also occurs in advanced cancers and plays a major role in contributing to the non-response to chemotherapy. 

Since the discovery of the P-lactam antibiotic penicillin G (Fig. 12.2-3) by Fleming in 1929, the use of antibiotics against pathogenic bacteria has increased dramatically. Penicillin G was initially used, which must be applied intravenously because of its instability in the stomach, but now penicillin V, which can be administered orally, has been introduced. However, as a result of the increasing resistance of bacteria, new antibiotics had to be developed. The semi-synthetic antibiotics, which often possess a broad spectrum of antibacterial activity, were produced by altering the side chain of penicillin G through acylation of the amine function of 6-aminopenicillanic acid (6-APA)[56. ... 

Bacterial infections are treated with antibiotics. There are many antibiotics available, but they fall into three major groups based on their mode of action inhibitors of bacterial nucleic acid synthesis inhibitors of cell wall synthesis and inhibition of bacterial protein synthesis. Resistance of bacteria to commonly-used antibiotics has become a major problem necessitating the development of new antibiotics. Tuberculosis infection is difficult to treat and requires a combination of at least three different antibiotics. 

Smiddy et al. (2005) confirmed higher baro-resistance of bacteria in oysters than in bnffer, which indicated that stndies of high-pressure-induced bacterial inactivation in bnffer systems may not predict inactivation of microorganisms in foods. Calci et al. (2005) indicated that 6-log redaction of Hepatitis A virus could be achieved via application of high pressure (350-400 MPa). Li et al. (2009) demonstrated that high-pressnre treatment (400 MPa, 5 min, 0°C) of oysters contaminated with murine norovirns-1 could reduce the levels of contaminant to undetectable levels. 

Smiddy, M., O Gorman, L., Sleator, D.R., Kerry, P.J., Patterson, E.M., Kelly, L.A., and HUl, C. 2005. Greater high-pressure resistance of bacteria in oysters than in buffer. Innovative Food Science and Emerging Technologies 6 83-90. 

Describe the mechanisms underlying the resistance of bacteria to beta-lactam antibiotics. 

The increased resistance of bacteria to antibiotic therapy is a growing concern for doctors and medical officials worldwide. In the last two decades bacteria have developed resistance to almost all the commercially available antibiotics and the number of new antibiotics expected to enter the market is limited. One of the modes by which bacteria exert this resistance is their ability to develop biofilms. Biofilms are bacterial communities encased in a hydrated polymeric matrix. Biofilm development is known to follow a series of complex but discrete and well-regulated steps (Fig. 4.1) (1) microbial attachment to the surface, (2) growth and aggregation of cells into microcolonies, (3) maturation, and (4) dissemination of progeny cells for new colony formalion (87,88). 

There are many reports available dealing with the acquired resistance of bacteria to novobiocin [105-108] and, in view of the rapidity with which resistance develops, the antibiotic is often administered in combination with other antibiotics. However, it has also been reported that an organism resistant to novobiocin is usually sensitive to other commonly-used anti-... 

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