Antibiotic Resistance Enzyme Caught In The Act

Resistance to an entire class of antibiotics—aminoglycosides—has the potential to spread to many types of bacteria, according to new biochemistry research (Science Daily, April 7, 2014).

By Jaime Abella Sison, DVM, FPCVFP

A mobile gene called NpmA was discovered in E. coli bacteria isolated from a Japanese patient several years ago. The global spread of NpmA and related antibiotic resistance enzymes could disable an entire class of tools doctors use to fight serious or life-threatening infections.

Using X-ray crystallography, researchers at Emory University School of Medicine (Atlanta, Georgia, USA) made an atomic-scale snapshot of how the enzymes encoded by NpmA interacts with part of the ribosome, protein factories essential for all cells to function. NpmA imparts a tiny chemical change that makes the ribosome, and the bacteria, resistant to the drugs’ effects.

The results, published in the PNAS (Proceedings of the National Academy of Sciences) Early Edition, provide clues to the threat NpmA poses, but also reveal potential targets for the development of drugs that could overcome resistance from this group of enzymes.

The first author of the paper is postdoctoral fellow Jack A. Dunkle, Ph.D. Co-senior authors are assistant professor of biochemistry Christine Dunham, Ph.D. and associate professor of biochemistry Graeme Conn, Ph.D.

Doctors generally use aminoglycoside antibiotics only for serious infections because they can be toxic to the kidney and inner ear. But the growing problem of resistance to other types of antibiotics has sparked renewed interest in aminoglycosides’ clinical use.

Examples of aminoglycosides include streptomycin (the first antibiotic remedy for tuberculosis), kanamycin, tobramycin (often used in cystic fibrosis), gentamicin, and neomycin.

Aminoglycosides bind to ribosomes, interfering with protein production in bacteria. Most mobile genes that confer aminoglycoside resistance chemically alter the antibiotics, and are active against only a few antibiotics. Instead, the NpmA-encoded enzyme modifies the ribosome so that aminoglycoside antibiotics don’t interfere with it anymore. That’s why it’s more dangerous. Another feature of NpmA that makes it dangerous is that it ribosomes. The information the Emory team obtained suggests that NpmA, found in E. coli, could easily work in other types of bacteria.

The structures of ribosome alone and the NpmA enzyme alone were already available: the Emory team was able to capture the two together in a “pre-catalytic state.”

Aminoglycosides are naturally produced by certain types of soil bacteria against other bacteria, and the producer bacteria have to make a resistance enzyme to prevent self-poisoning. Scientists hypothesize that the genes that encode this type of resistance enzymes in pathogenic bacteria were originally acquired from an aminoglycoside producer, Conn says.

AG-CO PRODUCTS IN POULTRY DIETS REDUCE EMISSIONS – Adding agricultural co-products to poultry diets has the potential to reduce greenhouse gas emissions from poultry production— provided that most of these co-products remain low and supplies
are adequate, according to the British Society of Animal Science (All About Feed, April 3, 2014).

Scientists from the Newcastle and Cranfield Universities carried out a joint study to compare the Global Warming Potential (GWP) of broiler meat and eggs with standard soya-based diets with alternative diets including processed animal protein (PAP) (broilers only) or dried distillers’ grains with solubles (DDGS).

Agricultural co-products—including PAP from the pig industry and DDGS from bioethanol production—are seen as potential alternative feed ingredients in the poultry industry. Using
alternative protein sources enables producers to replace the use of soya, the cultivation of which causes high greenhouse gas emissions which are related to land use change.

Applying a Life Cycle Assessment (LCA) model of both systems, the researchers made calculations based on typical dietary and production data provided by the broiler and egg
industries. In the alternative diets, the soya inclusion was reduced and other ingredients were adjusted to maintain the energy and nutrient levels in the diets, most notably essential  amino acids (AA), although the non-essential AAs could increase.

Two inclusion levels of each co-product were applied: ‘Realistic’ and ‘Extreme’, and it was assumed that using the alternative diets would not change animal performance. Economic allocation was used to partition the GWP between co-products (DDGS plus bioethanol, PAP plus tallow plus pig carcass).

“The relative values of these co-products vary depending on supply and demand,” said Dr. Leinonen, who led the research. He added, “Allowing the use of PAP—currently banned—as poultry feed can be expected to increase its price considerably. So the results were calculated for a range of possible values of the co-products relative to the main product.”

The team found that the GWP of broiler meat could be reduced by up to 11 percent, with low relative economic values of PAP. DDGS was only beneficial in the layer diets and only when the economic allocation to DDGS was less than 35 percent.

“The negative effect of DDGS in broilers was partly causedby higher nitrogen (N) excretion rates, causing higher nitrous oxide (N2O) emissions,” said Dr. Leinonen. He added that an
assumption was made that the alternative ingredients have no effect on bird performance.

“Quantification of additional environmental criteria is needed to make a holistic judgment on the environmental impacts of these ingredients.”

This story appeared in Agriculture Monthly’s June 2014 issue. 

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