Enzymes, plasmid-encoded

It has been shown that an AAC enzyme variant (AAC (6 )-Ib-cr, cr for ciprofloxacin resistance) found in various Enterobacteriaceae is capable of A-acetylating fluoroquinolones with an unmodified piperazinyl substituent at the amino nitrogen. Although the increase in MIC is low, this plasmid encoded quinolone resistance determinant can augment further development of clinically relevant resistance. 

Acetyl-CoA is also utilized as a cofactor to modify chloramphenicol by O-acetyltranferases (CATs). These enzymes have been found in many different bacterial genera and are usually plasmid encoded in clinical isolates. Furthermore, streptogramin type A antibiotics are acetylatedby Vat enzymes that occur on plasmids in staphylococci and enterococci. 

Nucleotidylation - the addition of adenylate-residues by Lnu enzymes - can also be the cause of resistance to lincosamide antibiotics in staphylococci and enterococci. A plasmid encoded ADP-ribosylating transferase (Arr-2) that leads to rifampicin resistance has been detected in various Enterobacteriaceae as well as in Pseudomonas aeruginosa. 

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. 

Schenk S, A Hoelz, B Krauss, K Decker (1998) Gene structures and properties of enzymes of the plasmid-encoded nicotine catabolism of Arthrobacter nicotinovorans. J Mol Biol 284 1323-1339. 

These substances resemble 3-lactam molecules (Figure 43-7) but they have very weak antibacterial action. They are potent inhibitors of many but not all bacterial 3 lactamases and can protect hydrolyzable penicillins from inactivation by these enzymes. -Lactamase inhibitors are most active against Ambler class A lactamases (plasmid-encoded transposable element [ ] lactamases in particular), such as those produced by staphylococci, H influenzae, N gonorrhoeae, salmonella, shigella, E coli, and pneumoniae. They are not good inhibitors of class lactamases, which typically are chromosomally encoded and inducible, produced by enterobacter, citrobacter, serratia, and pseudomonas, but they do inhibit chromosomal 3 lactamases of bacteroides and moraxella. 

Low-level resistance to chloramphenicol may emerge from large populations of chloramphenicol-susceptible cells by selection of mutants that are less permeable to the drug. Clinically significant resistance is due to production of chloramphenicol acetyltransferase, a plasmid-encoded enzyme that inactivates the drug. 

Resistance can emerge by mutation, though more commonly it is due to plasmid-encoded trimethoprim-resistant dihydrofolate reductases. These resistant enzymes may be located within transposons on conjugative plasmids that exhibit a broad host range, accounting for rapid and widespread dissemination of trimethoprim resistance among numerous bacterial species. 

Further modifications using the same strain of ODC S. cerevisiae reconstituted a bacterial/plant polyamine synthesis pathway in yeast [41], The ODC strain was transformed with plasmids encoding arginine decarboxylase and ag-matine ureohydrolase, which conferred polyamine-independent growth on the recombinant microbe. A similar construction could be used to screen for inhibitors of the homologous enzymes from Apicomplexan protozoa, which synthesize poly amines through this pathway [42]. 

Abril, M.A., Michan, C., Timmis, K.N., and Ramos, J.L., Regulator and enzyme specificities of the TOL plasmid-encoded upper pathway for degradation of aromatic hydrocarbons and expansion of the substrate range of the pathway, J. Bacteriol., 171, 6782-6790, 1989. 

Fig. 8 Influence of affinity tags fused to levansucrase LevA773 on secretion by B. megaterium and enzyme activity. B. megaterium MS941 carrying the plasmids encoding LevA773 (lane 1),...

The lincosamides, lincomycin and clindamycin are active against Grampositive bacteria. Plasmid-mediated inactivation from enzymatic nucleo-tidylation occurs in some staphylococci. Plasmid-encoded enzymes can modify streptogramin A (O-acetyltransferase enzyme) and streptogramin B (hydrolase enzyme involved) in S. aureus [198, 199], There is no evidence that bacteria can circumvent the action of other antibiotics for example, mupirocin is not degraded [200]. 

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