Plasmids acquired

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. 

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). 

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. 

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. 

A third mechanism of plasmid transfer is by transformation, which is the ability of certain microorganisms to acquire naked DNA from the environment. This is limited to certain bacteria, notably Neisseria gonorrhoeae, which is naturally competent to acquire DNA in this manner. Neisseria gonorrhoeae strains have the ability to recognize DNA from their own species, and are thus selective in their acquisition of naked DNA from the environment. 

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. 

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... 

DNA plasmid-based treatment ( gene therapy ) is considered an alternative to the one based on classical chemical drugs or proteins recovered from recombinant cells. Treatment of acquired and inherent genetic diseases as well as the use of DNA for the purpose of vaccination are potential applications of plasmid DNA (pDNA). The plasmid carries information that allows protein expression in the targeted human cells as well as eukaryotic regulatory elements and specific prokaryotic sequences that control replication in the host cell, see Fig. 10. Formulation is required for ex- or in-vivo administration. Selected systems for gene expression can be viral or non-viral. 

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. 

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. 

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. 

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