Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find missing enzyme for tuberculosis iron scavenging pathway

31.03.2005


Scientists have discovered that a protein that was originally believed to be involved in tuberculosis antibiotic resistance is actually a "missing enzyme" from the biosynthetic pathway for an agent used by the bacteria to scavenge iron.



The research appears as the "Paper of the Week" in the April 8 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for more morbidity in humans than any other bacteria. The emergence of multi-drug resistant strains of M. tuberculosis has prompted the search for new drug targets and a better understanding of the mechanism of resistance in this bacterium.


Several spans of DNA in the M. tuberculosis genome have been annotated as antibiotic resistance genes due to their sequence similarity to existing antibiotic resistance genes. Dr. Edward N. Baker of the University of Auckland in New Zealand explains, "Generally the sequence of the open reading frame is compared with the sequences of genes for other proteins (most of which are from different species) in sequence databases. If a close match is found, it is assumed that the function is the same or similar."

Rv1347c is one of these annotated antibiotic resistance genes in M. tuberculosis. It encodes a putative aminoglycoside N-acetyltransferase that is thought to be involved in resistance to aminoglycoside antibiotics such as streptomycin.

"The aminoglycoside antibiotics have sugar rings with amino groups attached," explains Dr. Baker. "The N-acetyltransferase chemically modifies the sugar amino group by transferring an acetyl group to it. This inactivates the antibiotic because it can no longer fit into its target."

However, in vitro biochemical assays have failed to demonstrate aminoglycoside N-acetyltransferase activity in Rv1347c. By solving the three-dimensional structure of Rv1347c, Dr. Baker and his colleagues have discovered that the enzyme most likely plays an entirely different role in M. tuberculosis.

"What the structure showed, when combined with careful analysis of the sequence, its neighbors in the genome, and the fact that its gene was also regulated by iron, was that Rv1347c was almost certainly a "missing enzyme" from the pathway for biosynthesis of the iron scavenging agent mycobactin," recalls Dr. Baker.

"Mycobactin is a small molecule which binds iron very tightly. Bacteria synthesize it so that they can acquire the iron they need to grow – it is secreted out into the external environment where it scavenges iron and then (with iron bound to it) it is taken up by the bacterium again."

Although Rv1347c is not involved in antibiotic resistance, it still remains a target for the design of new anti-TB drugs. "Enzymes that synthesize mycobactin are drug targets, because if mycobactin biosynthesis is stopped, the bacterium cannot acquire the iron that it needs for survival," explains Dr. Baker. "Importantly this seems to be true even of the bacteria that are taken up by macrophages in the lung and enter a dormant state – these are the hardest to attack with drugs."

Nicole Kresge | EurekAlert!
Further information:
http://www.asbmb.org
http://www.jbc.org

More articles from Life Sciences:

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

nachricht Transforming plant cells from generalists to specialists
07.12.2016 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>