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:5/6/2017)... May 5, 2017 RAM Group ... a new breakthrough in biometric authentication based on ... mechanical properties to perform biometric authentication. These new sensors ... material created by Ram Group and its partners. This ... transportation, supply chains and security. Ram Group is ...
(Date:4/19/2017)... New York , April 19, 2017 ... competitive, as its vendor landscape is marked by the ... the market is however held by five major players ... Safran. Together these companies accounted for nearly 61% of ... of the leading companies in the global military biometrics ...
(Date:4/17/2017)... 17, 2017 NXT-ID, Inc. (NASDAQ: NXTD ... filing of its 2016 Annual Report on Form 10-K on Thursday ... ... available in the Investor Relations section of the Company,s website at ... website at http://www.sec.gov . 2016 Year Highlights: ...
Breaking Biology News(10 mins):
(Date:9/19/2017)... ... ... VetStem Biopharma ’s CEO and founder, Dr. Bob Harman DVM, MPVM, is featured in an ... A Rising Tide". Dr. Harman and Dr. Riordan met in 2003 and have remained ... potential of stem cell therapy and a fast friendship was formed. , Dr. Harman has ...
(Date:9/19/2017)... ... September 19, 2017 , ... One of the ... be eliminated, said Lyle Probst, President, CEO and Founder of ExcitePCR ™. ... other pathogen detection solutions, Probst said, “Sample preparation takes place inside our FireflyDX ...
(Date:9/19/2017)... ... 19, 2017 , ... Avomeen Analytical Services, an Ann Arbor ... Science Student Award. The scholarship program is dedicated to helping those who demonstrate ... costs of obtaining their science education. , Avomeen began the annual scholarship program ...
(Date:9/19/2017)... ... September 19, 2017 , ... ... Department of Financial Services (NYS DFS) cybersecurity regulations have transitioned into ... and insurance organizations operating in the state (“Covered Entities”) to conduct an ...
Breaking Biology Technology: