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NDM-1 (cont.)

What Causes NDM-1 to Be Produced in Bacteria?

The genetic code (blaNDM-1) located on either a plasmid or integrated into the bacterial chromosome is responsible for the synthesis of the enzyme NDM-1. Researchers suggest that environmental pressures, such as the use or overuse of antibiotics, selected for bacteria that could synthesize this enzyme to survive. Some speculate that because there are fewer restrictions on the use of antibiotics in many countries, antibiotic-resistant strains are likely to be produced in these countries; with NDM-1, some investigators suggest India is where this genetic element first developed.

Figure 1 is a schematic diagram that shows the various methods bacteria use to transfer genetic material among different bacterial types. The first method, transformation, occurs when a bacterium's cell wall breaks down during bacterial cell death and the bacterial genetic material (both chromosomal and plasmid) are released into the environment. Other nearby bacteria then can absorb the genetic material and incorporate the absorbed genes into its own plasmids or chromosome.

The second method, conjugation, occurs when two bacteria share a connection through their cell walls that allows genetic material (plasmids or gene fragments) to pass into another bacterium that can incorporate the plasmid or gene fragments into other plasmids or the chromosome.

The last method, transduction, is more complicated. The first step involves a bacteriophage (a type of virus that infects bacteria) that attaches and injects its genome (Fig. 1, white line) into a bacterium. The bacteriophage genome then "takes over" the bacterial cell and synthesizes bacteriophage parts that are reassembled into new bacteriophages. However, during reassembly, sometimes genes from plasmids or the bacterial chromosome genetic material are mistakenly put into the bacteriophage particle (Fig.1, hexagonal-shaped structure, termed a capsid) instead of only viral genes. After reassembly is done, the bacteriophage breaks open the bacterial cell wall and the new bacteriophages then can reinfect other bacteria. Not all bacteriophage-infected bacteria die; some survive. Those bacteria that are infected with bacteriophage genetic material that contained genes from bacterial plasmids or from the bacterial chromosome then can incorporate the plasmid or chromosomal genes into their own plasmids or chromosome.

These types of genetic transfers are responsible for the synthesis of the multiple enzymes like NDM-1 that allow bacteria to become resistant to many antibiotics. Such antibiotic-resistant genes are often closely linked together, and even multiple linked genes can be transferred by these methods at the same time.

Figure 1. Mechanisms that allow genes that code for drug resistance to be shared among various bacterial strains and different bacterial genera

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