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:2/2/2016)... Calif. , Feb. 2, 2016  Based ... market, Frost & Sullivan recognizes US-based Intelligent Retinal ... Frost & Sullivan Award for New Product Innovation. ... in North America , is ... the rapidly growing diabetic retinopathy market. The IRIS ...
(Date:1/28/2016)... (NASDAQ: SYNA ), a leading developer of human interface solutions, ... 2015. --> --> Net ... compared to the comparable quarter last year to $470.5 million. Net ... or $0.93 per diluted share. --> ... fiscal 2016 grew 9 percent over the prior year period to ...
(Date:1/22/2016)... , January 22, 2016 ... the addition of the  "Global Behavioral ... offering. --> http://www.researchandmarkets.com/research/4lmf2s/global_behavioral ) ... "Global Behavioral Biometric Market 2016-2020"  report ... Research and Markets ( http://www.researchandmarkets.com/research/4lmf2s/global_behavioral ) has ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... 11, 2016  Vermillion, Inc. (NASDAQ: VRML ), ... announced the formation of the Steering Committee for its ... --> Pelvic masses can present physicians and ... Once pregnancy is ruled out, pelvic masses may include ... endometriosis, benign ovarian tumors and gastrointestinal and urinary tract ...
(Date:2/11/2016)... ATLANTA , Feb. 11, 2016  Spectra BioPharma ... Organization (CSO) that provides biopharma companies the experience, ... implement and deploy outsourced sales teams. Created in ... team addresses both the strategic and tactical needs ... innovative sales solutions through both personal and non-personal ...
(Date:2/11/2016)... SANTA CRUZ, Calif. , Feb. 11, 2016 /PRNewswire/ ... accepting applications to its beta program for a planned ... co-founder, will present the company,s metagenomic genome assembly method ... 2016 Advances in Genome Biology & Technology conference in ... novo  assembly of these highly complex datasets is difficult. ...
(Date:2/11/2016)... , ... February 11, 2016 , ... ... more than 150 years, continues today to pursue the highest level of accuracy ... analytical instruments: the AR9 Refractometer and the AR5 Refractometer. Accurate, reliable and ...
Breaking Biology Technology: