Resistance plasmid-acquired

Over 4 decades, between 1960 and 2000, the development of new antibiotics used well characterized basic structures for partial synthetic modifications, primarily to overcome resistance by increasing the pharmacodynamic properties and, secondarily, to improve the pharmacokinetic profile of older compounds. However, bacteria rapidly responded by acquiring additional genetic alterations either as mutations or by accumulating resistance genes as part of mobile genetic elements ( integrons) on transferable resistance plasmids. 

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. 

Duplication ofDHPS, with the second version of the enzyme being resistant to the sulphonamides, is the cause of plasmid-acquired resistance. Two different enzymes have been identified, both with lowered affinity for the antibiotic. 

Development of resistance to rifaximin is primarily due to a chromosomal one-step alteration in the drug target, DNA-dependent RNA polymerase. This differs from the plasmid-mediated resistance commonly acquired by bacteria to aminoglycoside antibiotics such as neomycin... 

Resistance can also be acquired when DNA responsible for nonsusceptibility (so-called resistance plasmid) is passed on from other resistant bacteria by conjugation or transduction. 

The role of enterococci in nosocomial infections is probably due to a variety of factors of which antimicrobial resistance appears to be a primary cause. Enterococci possess a broad spectrum of both natural (intrinsic) resistance and acquired (transferable) resistance (Franz et al. 2003). Examples of antibiotics to which the enterococci present an intrinsic resistance include the P-lactam antibiotics (third generation cephalosporins), sulphonamides and clindamycin and aminoglycosides in low levels (Eranz et al. 2003). Acquired resistance based on plasmids or transpo-sons acquisition has relevance for chloramphenicol, erythromycin, high levels of clindamycin, aminoglycosides, tetracycline, high levels of P-lactam antibiotics, fluoroquinolones and glycopeptides like vancomycin (Murray 1990 Leclercq 1997). In particular, vancomycin-resistant enterococci (VRE) pose a major problem... 

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... 

Generally resistance arises from both natural and spontaneous mutations, followed by multiplication of the resistant strains. Although some might argue that all resistance is acquired at some level, the acquisition of resistance genes requires that insertion occur either in the chromosome or plasmid, and a logical conclusion is that these insertion sites have been programmed, or have evolved, over time to accommodate molecular... 

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). 

Three genetic elements are responsible for acquired resistance chromosomes, plasmids and trarrsposons (Lewis 1989). Each of these will be considered in tiun. 

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). 

Acquired, non-plasmid-encoded resistance to biocides can result when bacteria are exposed to gradually increasing concentrations of a biocide. Examples are provided by highly QAC-resistant Serratia marcescens, and chlorhexidine-resistant Ps. mirabilis, Ps. aeruginosa md Ser. marcescens. 

If this is true, said the committee, and if these resistant bacteria reach consumers of meat, there would be an increased risk of infection by resistant pathogens, or there would be an increased likelihood of acquiring a nonpathogenic resistant organism that could transmit infectious resistance to pathogens. "Infectious resistance" refers to the transfer of resistant genes between bacterial cells by means of plasmids or episomes. The committee concluded that not enough information was avialable on these issues to determine the effects on human health. 

Acquired resistance implies a change in the DNA of the bacteria that results in the appearance of new characteristic features. Such resistance is achieved in two ways mutation of chromosomes in bacteria or acquisition of new pieces of DNA (plasmid) that code for a function of resistance. 

There are several mechanisms by which plasmids can serve as the vehicle to transfer resistance determinants to sensitive bacteria. These include transduction, transformation, and conjugation. Resistance that is acquired by this type of horizontal transfer can become rapidly and widely disseminated. 

DNA transfer of drug resistance Of particular clinical concern is resistance acquired due to DNA transfer from one organism to another. Resistance properties are usually encoded in extrachro-mosomal R factors (plasmids). These may enter cells by processes such as transduction (phage-mediated), transformation or, most importantly, bacterial conjugation. 

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-... 

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