Transposons acquired resistance

Resistance to Tetracyclines. The tetracyclines stiU provide inexpensive and effective treatment for several microbial infections, but the emergence of acquired resistance to this class of antibiotic has limited their clinical usehilness. Studies to define the molecular basis of resistance are underway so that derivatives having improved antibacterial spectra and less susceptibiUty to bacterial resistance may be developed. Tetracyclines are antibiotics of choice for relatively few human infections encountered in daily clinical practice (104), largely as a result of the emergence of acquired tetracycline-resistance among clinically important bacteria (88,105,106). Acquired resistance occurs when resistant strains emerge from previously sensitive bacterial populations by acquisition of resistance genes which usually reside in plasmids and/or transposons (88,106,107). Furthermore, resistance deterrninants contained in transposons spread to, and become estabUshed in, diverse bacterial species (106). 

Acquired resistance. This occurs when bacteria which were previously susceptible become resistant, usually, but not always, after exposure to the antibiotic concerned. Intrirrsic resistance is always chromosomally mediated, whereas acquired resistance may occirr by mutations in the chromosome or by the acquisition of genes coding for resistance ftom an external source normally via a plasmid or transposon. Both types are clinically important and can result in treatment failure, although acquired resistance is more of a threat in the spread of antibiotic resistance (Russell Chopra 1996). 

Plasmids have the ability to transfer within and between species and can therefore be acquired from other bacteria as well as a consequence of cell division. This property makes plasmid-acquired resistance much more threatening in terms ofthe spread of antibiotic resistance than resistance acquired due to chromosomal mutation. Plasmids also harbour transposons (section 2.1.3), which enhances their ability to transfer antibiotic resistance genes. 

Acquired resistance to the glycopeptides is transposon-mediated and has so far been largely confined to the enterococci. This has been a problem clinically because many of these strains have been resistant to all other antibiotics and were thus effectively untreatable. Fortunately, the enterococci are not particularly pathogenic and infections have been confined largely to seriously ill, long-term hospital patients. Two types of acquired glycopeptide resistance have been described (Woodford et al. 1995). The VanA phenotype is resistant to vancomycin and teicoplanin, whereas VanB is resistant... 

Bacterial resistance to biocides (Table 13.2) is usually considered as being of two types (a) intrinsic (innate, natural), a natural property of an organism, or (b) acquired, either by chromosomal mutation or by the acquisition of plasmids or transposons. Intrinsic resistance to biocides is usually demonstrated by Gram-negative bacteria, mycobacteria and bacterial spores whereas acquired resistance can result by mutation or, more frequently, by the acquisition of genetic elements, e.g. plasmid- (or transposon-) mediated resistance to mercury compounds. Intrinsic resistance may also be exemplified by physiological (phenotypic) adaptation, a classical example of which is biofilm production. 

Acquired resistance to biocides results fiem genetie ehanges in a cell and arises either by mutation or by the acquisition of genetic material (plasmids, transposons) from another cell (Table 13.5). 

Unlike intrinsic resistance, which is usually expressed by chromosomal genes, acquired resistance arises as a consequence of mutations in chromosomal genes or by the acquisition of plasmids or transposons [6, 7, 157, 158]. Chromosomal mutations are associated with changes in the base se-... 

In contrast, acquired resistance may be the result of mutations in chromosomal genes or of the acquisition of plasmids and transposons. An acquired resistance arises from the selective pressure exerted on bacteria in terms of the application, including incorrect use or wrong prescriptions of antibiotics for chemotherapy. 

MECHANISMS OF BACTERIAL RESISTANCE TO PENICILLINS AND CEPHALOSPORINS A sensitive strain may acquire resistance by mutations that decrease the affinity of PBPs for the antibiotic. Because /5-lactam antibiotics inhibit many different PBPs, their affinity for several PBPs must decrease to confer resistance. Methidllin-resistant S. aureus are resistant via acquisition of an additional high-molecular-weight PBP (via a transposon) with a very low affinity for all /5-lactam antibiotics this mechanism is responsible for methicillin resistance in the coagu-lase-negative staphylococci. 

Acquired resistance to biocides arises by the acquisition of extrachromoso-mal genetic elements (plasmids and transposons) or as a consequence of a chromosomal gene mutation [53, 236, 237]. Acquired resistance to chromosomal mutation can arise when bacteria are sequentially exposed to increasing concentrations of a biocide. 

Acquired microbial resistance has been extensively investigated with various antibiotics, but similar studies with biocides are fewer and more recent. It has been confirmed that many biocides can also be rendered meffective or less effective by acquired microbial resistance. This acquired resistance to both biocides and antibiotics may be genetic and/or biochemical [16, 26]. Chromosomal gene mutation and acquisition of plasmids and transposons by the microbes are the genetic modes that have been observed. As shown in Table I, plasmid-mediated biocide resistance can occur by... 

Staphylococcus aureus cells can acquire large DNA fragments containing the mecA gene which encodes a complete new penicillin binding protein 2A (PBP 2A), as part of a transposon. PBP2A can substitute the natural set of penicillin-sensitive PBPs thereby mediating a complete cross resistance to all (3-lactam antibiotics. 

In general terms, bacterial resistance to antibacterial agents can be considered as being either intrinsic (innate, a natural property) or acquired, for example, by mutation or by the acquisition of a plasmid or transposon (jumping gene) [105]. Resistance to mercury [103, 122-125] and to other cations and anions [103, 122, 123, 125] is well characterized. The mechanisms involved in resistance to some metals, including silver, are summarized in Table 7.1. 

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