Navigation Links
Scientists find missing enzyme for tuberculosis iron scavenging pathway

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."


'"/>

Source:American Society for Biochemistry and Molecular Biology


Related biology news :

1. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
2. Scientists Replicate Hepatitis C Virus in Laboratory
3. Scientists detect probable genetic cause of some Parkinsons disease cases
4. Scientists seek answers on what activates deadly anthrax spores
5. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
6. Scientists collaborate to assess health of global environment
7. Scientists decipher genome of fungus that can cause life-threatening infections
8. Scientists discover the cellular roots of graying hair
9. Scientists rid stem cell culture of key animal cells
10. Scientists develop new color-coded test for protein folding
11. Scientists identify genetic pathways essential to RNA interference
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/22/2019)... ... February 21, 2019 , ... The Virginia Commonwealth University ... agreement establishing a collaborative program to work toward applications of Fuzionaire Dx’s proprietary ... lead candidates and will explore Fuzionaire Dx’s platform as a unique tool for ...
(Date:2/19/2019)... MONTREAL (PRWEB) , ... February 18, 2019 , ... The Idea, Emma came home from ... Her web developer dad figured there must be an app out there to make her ... an app of her own: Emma’s Words. , The idea is simple enough: help children ...
(Date:2/13/2019)... ... February 13, 2019 , ... ... science of medical marijuana legally through patient clinical trials and research, announced that ... FDA grants Fast Track Designation to help expedite the review and approval of ...
Breaking Biology News(10 mins):
(Date:2/2/2019)... BOSTON (PRWEB) , ... January 31, 2019 , ... The ... in Boston this spring to showcase their tools to the largest gathering of ... IBM, DataRobot, SAS, S&P Global and Mathworks are partnering with the Open Data ...
(Date:1/30/2019)... ... January 29, 2019 , ... MabPlex ... (CDMO) serving the global biopharmaceutical and biotechnology industries with sites in China and ... by multiple global investors lead by China's State Development & Investment Corporation (SDIC) ...
(Date:1/30/2019)... ... 30, 2019 , ... The Society for Laboratory Automation and ... best practices for laboratory automation and screening. This year the conference will be ... Visikol will be at booth #345 and throughout the conference will highlight its ...
(Date:1/24/2019)... ... January 22, 2019 , ... Dr. Douglas Stramel of Advanced Care Veterinary ... Therapy System (V-PET™) for nearly three years. A proponent of Regenerative Medicine, ... 2007 and began using V-PET™ 2016. V-PET™ is a gravity filtration-based platelet therapy ...
Breaking Biology Technology: