Transposons resistance

Shaw, J. H., and Clewell, D. B. (1985). Complete nucleotide sequence of macrolide-lincosamide-streptogramin B-resistance transposon Tn917 in Streptococcus faecalis. J. Bacterial. 164,782-796. 

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). 

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. 

Bacteria can develop resistance to antimicrobial agents as a result of mutational changes in the chromosome or via the acquisition of genetic material (resistance genes carried on plasmids or transposons or the recombination of foreign DNA into the chromosome) (Fig. 2). 

Resistance to trimethoprim can be due to the acquisition of plasmid encoded non-allelic variants of the chromosomal DHFR enzyme that are antibiotic unsusceptible. The genes may be part of transposons that then insert into the chromosome. For instance, in gram-negative bacteria the most widespread gene is dhfrl on transposon Tn7. 

Accessory DHPS enzymes confer resistance to sulfonamides. Two different types encoded by the genes sull (located on transposons) and sulll (located on plasmids) have been described. These resistance determinants are often genetically linked to trimethoprim resistance genes. Therefore, the combination of sulfonamide antibiotics with trimethoprim does not prevent resistance selection. 

Transposons are mobile DNA elements (sizes 2.5-23 kbp) that move from one place to another in the chromosome or onto extrachromosomal genetic elements within the same cell. They are flanked by inverted repeats at then-ends and encode among other proteins a transposase that is needed for the transposition process. Resistance genes in the transposon are often parts of integrons. These are structures that cany an integrase responsible for the insertion of the resistance gene cassettes into the integron. 

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. 

Resistance may also be chromosomally mediated, t Multiple resistance genes may be carried on a transposon. 

Plasmid- and transposon-mediated resistance is akin to that described for the sulphonamides, where the sensitive step is bypassed by duplication of the target with a resistant version. Many different resistant enzymes have been identified thus far. 

Plasmid- or transposon-encoded ribosomal protection factors are a second mechanism of resistance to the tetracyclines. These proteins are believed to alter the tetracycline binding site on the 308 ribosomal subunit, lowering the affinity for the drugs. 

Plasmid- or transposon-mediated resistance common to the MLS group is due to RNA methylase genes emiA, emiB and ermC) which code for the methylation of an adenine residue in 23 S rRNA. Methylation prevents the drugs from binding to the 508 ribosomal subunit and confers resistance to all MLS antibiotics. 

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... 

Fig. 9.4 Organization of glycopeptide-resistance genes in transposon Tnl546. IR, invested repeats HPK, histidine protein kinase TcR, low level teicoplanin resistance.

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). 

Pillai SD, Pepper IL (1991) Transposon Tn5 as an identifiable marker in rhizobia survival and genetic stability of Tn5 mutant bean rhizobia under temperature stressed conditions in desert soils. Microbial Ecol 21 21-33 Pote J, Ceccherini MT, Van VT, Rosselli W, Wildi W, Simonet P, Vogel TM (2003) Fate and transport of antibiotic resistance genes in saturated soil columns. Eur J Soil Biol 39 65-71... 

Transposon integration mutagenesis can be used to allow the selection of metalloid-resistant mutants with enhanced MICs.147 Ledgham et al.148 found a transposon-disrupted gene in a mutant - with a three-fold increase in Se-resistance - that encoded a protein from a member of the DedA family of membrane proteins that was implicated in the uptake of selenite through cell membranes. This is a reasonable hypothesis for how metalloid resistance occurs in some microorganisms. 

Antibiotics are routinely added to animal feed in conventional agriculture. This can have various effects on humans. Direct transmission of antibiotic residues in animal products to people may cause direct toxicity, i.e. allergies, or lead to the emergence of resistant strains of bacteria. Another threat is antibiotic-resistant forms of bacteria harmful to mankind that might appear in animals and pass from them to humans (Smith 1974), or may impart resistance to other bacteria by plasmid or transposon interchange (Franco et al. 1990). The resulting dmg-resistant and harmful micro-organisms can then not be treated successfully (Silverstone 1993). 

Spontaneous antibiotic-resistant mutants of these organisms are suitable for initial root colonization studies however, transposon mutants will be more suitable for detailed laboratory and field studies. This procedure is useful for sorting out the genetic relationships of these organisms and for determining the mechanisms controlling toxin production. 

Transposition occurs when transposons (genetic elements capable of moving between bacteria, plasmids or between chromosomal DNA and plasmids) migrate to confer resistance determinants to another organism. 

Arthur, M. Molinas, C. Depardieu, E Courvalin, P Characterization of Tnl546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J. Bacteriol., 175, 117-127 (1993)... 

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