Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print Researchers analyze how new anti-MRSA abtibiotics function

Researchers analyze how new anti-MRSA abtibiotics function

July 29, 2008

A new paper by Shahriar Mobashery, Navari Family Professor in Life Sciences at the University of Notre Dame, and researchers in his lab provides important insights into promising new antibiotics aimed at combating MRSA.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major global health threat that kills approximately 20,000 people in the U.S. alone each year.




Mobashery is a world-renowned expert in antibiotic resistance and enzyme inhibitors and he and his research team have long probed the nuances of MRSA as a superbacterium.

The Notre Dame team investigated two new anti-MRSA β-Lactam antibiotics from the pharmaceutical company Cerexa Inc., which are currently undergoing clinical trails. Both are broad-spectrum antibiotics, but their activities against MRSA and multi-drug-resistant MRSA have been especially noteworthy.

Although current media attention to MRSA may make it seem to be a recent development, the first strain that came to be known as MRSA actually emerged in 1961 in the United Kingdom. This difficult strain of Staphylococcus aureus became a global scourge within a span of a mere few years. Whereas previously Staphylococcus aureus was exquisitely sensitive to β-Lactam antibiotics, a class that includes penicillins (such as methicillin), this variant became resistant to all of the commercially available members of this class of antibiotics. Clinicians had to turn to second lines of antibiotics, which were substantially less effective and often were toxic to the human host.

By the 1980s and 1990s, MRSA had become a serious clinical problem, dreaded by clinicians in health care facilities, prisons and nursing homes. Of late, a new variant of community onset of antibiotic-resistant staph infections emerged outside of institutions.

"For the past 50 or 60 years, we've been able to stay one step ahead of traditional infections," Mobashery said. "However, there are cases of resistance to all eight major existing classes of antibiotics. Actually resistant bacteria are often resistant to multiple classes of antibiotics, not just one or two."

For just over 40 years, scientists have known that bacteria possess a cell wall. Since the health and integrity of the cell wall are critical to the survival of these organisms, it is not surprising that many antibiotics work by either impairing biosynthesis of the cell wall, or simply bind to it to inhibit full structural maturation. In 2006, Mobashery and his team of researchers provided the first clear understanding of the structure of peptidoglycan, the building unit of the bacterial cell wall.

Peptidoglycan, a mesh-like network, is the building block of the bacterial cell wall and neighboring peptidoglycans undergo a so-called "cross-linking" reaction to generate the rigid entity known as the cell wall. Since bacteria cannot regulate their internal pressure, bacterial cells would burst apart and die if cross-linking did not occur.

β-Lactam (e.g., penicillin) and glycopeptide (e.g., vancomycin) antibiotics are designed to impair the bacterial cell wall and inhibit the process of cross-linking, causing bacterial cells to burst and die.

Mobashery and his team have been focusing on a unique protein called penicillin-binding protein 2a (PBP 2a) that MRSA carries on its cell membrane. Previous research has shown that PBP 2a performs the critical cell wall cross-linking reaction.

Mobashery has previously reported that PBP 2a exists in "closed and open" forms. The open form is needed for the physiological functioning of PBP 2a, but the closed form is responsible for the antibiotic resistance manifestations. When the protein interacts with the cell wall at a specific location on its surface, it opens up to carry out the physiological function.

In their latest paper, Mobashery and his team reveal that the new Cerexa antibiotics appear to interact with PBP 2a in a unique way. The antibiotics mimic some of the interactions of the cell wall with PBP 2a, whereby the enzyme is "tricked" to open up as it attempts its physiological function. Once this opening of PBP 2a takes place, its function is inhibited by the novel antibiotics, resulting in bacterial cell death. "Both antibiotics are highly effective in killing MRSA," Mobashery said. "It's a promise that awaits the outcome of the clinical trials."

University of Notre Dame



Related Antibiotics Current Events and Antibiotics News Articles Antibiotics Current Events and Antibiotics News RSS Antibiotics Current Events and Antibiotics News RSS
UCLA researchers reconstitute enzyme that synthesizes cholesterol drug lovastatin
Researchers from the UCLA Henry Samueli School of Engineering and Applied Science have for the first time successfully reconstituted in the laboratory the enzyme responsible for producing the blockbuster cholesterol-lowering drug lovastatin.

Progress made on group B streptococcus vaccine
Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have completed a Phase II clinical study that indicates a vaccine to prevent Group B Streptococcus (GBS) infection is possible.

Henry Ford Hospital study: A MRSA strain linked to high death rates
A strain of MRSA that causes bloodstream infections is five times more lethal than other strains and has shown to have some resistance to the potent antibiotic drug vancomycin used to treat MRSA, according to a Henry Ford Hospital study.

Bacteria 'launch a shield' to resist attack
Researchers from the University of Copenhagen and the Technical University of Denmark along with other collaborators in Denmark and the US found that the bacterium Pseudomonas aeruginosa can 'switch on' production of molecules that kill white blood cells - preventing the bacteria being eliminated by the body's immune system.

Pumpkin skin may scare away germs
The skin of that pumpkin you carve into a Jack-o'-Lantern to scare away ghosts and goblins on Halloween contains a substance that could put a scare into microbes that cause millions of cases of yeast infections in adults and infants each year.

Deadly stomach infection rising in community settings, Mayo Clinic study finds
Mayo Clinic researchers have found that a sometimes deadly stomach bug, Clostridium difficile is on the rise in outpatient settings.

New clinical guidelines for exacerbations in cystic fibrosis
The American Thoracic Society has released new clinical guidelines for the treatment of exacerbations in cystic fibrosis based on a review of the literature on current clinical practices.

Eating right, not supplements, is best at keeping your good bacteria healthy, dietitian says
Healthy eating, not supplements, is the best way to keep the good bacteria in your gut healthy, says a dietitian and researcher.

3-day course of antibiotics may be sufficient following tonsillectomy
Children who receive a three-day course of antibiotics following tonsillectomy rather than a seven-day course appear to have no differences in pain or how quickly they return to a normal diet and activity level.

Scientists visualize assembly line gears in ribosomes, cell's protein factory
Even as research on the ribosome, one of the cell's most basic machines, is recognized with a Nobel Prize, scientists continue to achieve new insights on the way ribosomes work.
More Antibiotics Current Events and Antibiotics News Articles
Fish Mox (Amoxicillin 250 mg) - 100 Caps

Fish Mox (Amoxicillin 250 mg) - 100 Caps
by THOMAS LABS

Fish-Mox exerts a bactericidal action on gram positive and some gram negative bacteria. Useful for control of some common bacterial diseases of fish including aeromonas and pseudomonas genera and mysobacterial group (gill diseases, chondrococcus). Add contents of one capsule (250 mg) into aquarium for each 10 gallons of water to be treated. Repeat in 24 hours. It is suggested that a partial water change be made between treatments. While duration of treatment depends on type and severity of infection, it is recommended that extended medication baths continue for a minimum of 5 days & for not more than 10 days. Discontinue treatment if no improvement is noted within 5 days. To remove harmless yellow color, change 20% of water and use charcoal filter until clear.

Antibiotics Simplified

Antibiotics Simplified
by Jason Gallagher (Author)

Antibiotics Simplified is a succinct guide designed to bridge knowledge gained in basic sciences courses with clinical practice in infectious diseases. Introductory chapters explain the rationale behind the treatment of infectious diseases, describe a system for selecting antimicrobial agents and briefly review basic microbiology. Later chapters present relevant characteristics of drug classes, emphasizing clinical "pearls" for individual agents, and also include content on antifungals. The concise nature of the text allows for emphasis on key points, allowing readers to extract the most important characteristics of anti-infective drugs from the larger mass of material that they learn from detailed pharmacology textbooks. This is an ideal handbook for students as well as practicing...

First Aid Only Triple Antibiotic Ointment Pack, 0.5 Gram, 25-Count Boxes (Pack of 3)

First Aid Only Triple Antibiotic Ointment Pack, 0.5 Gram, 25-Count Boxes (Pack of 3)
by First Aid Only

Use this triple antibiotic ointment pack to treat all kinds of minor cuts, burns and abrasions. Helps prevent infection while it promotes healing. May be applied 2 to 3 times daily as the condition indicates. Active ingredients: neomycin and polymyxin B sulfates and bacitracin zinc ointment USP.

Fish Flex Cephalexin - 250 mg 100 capsules

Fish Flex Cephalexin - 250 mg 100 capsules
by THOMAS LABS

Fish-Flex is for use in aquariums for treatment of bacterial activity. Add contents of one capsule (250 mg) into aquarium for each 10 gallons of water to be treated. Repeat in 24 hours. It is suggested that a partial water change be made between treatments. While duration of treatment depends on type and severity of infection, it is recommended that extended medication baths continue for a minimum of 5 days & for not more than 10 days. Discontinue treatment if no improvement is noted within 5 days.

Antibiotics Pocketcard 2009

Antibiotics Pocketcard 2009
by H. Hof (Author)

Antibiotics pocketcard provides an initial choice of antimicrobial therapy for most common infections. These empirical therapies cover more than 90% of everyday scenarios. The reverse side of this durable plastic card shows a table of antimicrobial spectra for the most important antibiotics. **2009 edition, completely updated! **Initial choice of antimicrobials for: CNS, heart, blood, gastrointestinal tract, bones/joints, urogenital tract, eye, ENT, skin/soft tissue diseases, fever of unknown origin. **Antimicrobial agents against selected bacteria, e.g. streptococci, staphylococci.

Fish Mox Forte 500 mg x 100 ct

Fish Mox Forte 500 mg x 100 ct
by THOMAS LABS

Fish-Mox Forte (Amoxicillin) exerts a bacterial action on gram-positive and some gram-negative bacteria.

Antibiotic Essentials 2009

Antibiotic Essentials 2009
by Burke Cunha MD (Author)

Antibiotic Essentials is a concise, practical, and authoritative guide to the treatment and prevention of infectious diseases commonly encountered in adults. It covers 542 clinical infectious disease syndromes, HIV infection, 134 detailed drug summaries, pediatric infectious diseases, and a chest x-ray atlas. Topics include: Empiric Therapy Based on Clinical Syndrome; Initial Therapy Based on Isolates; Pending Susceptibility Testing; HIV Infection; Fungi, Parasites, Unusual Organisms; Antibiotic Prophylaxis and Immunizations; Drug Summaries

Antibiotic Basics for Clinicians: Choosing the Right Antibacterial Agent (Point (Lippincott Williams & Wilkins))

Antibiotic Basics for Clinicians: Choosing the Right Antibacterial Agent (Point (Lippincott Williams & Wilkins))
by Alan R Hauser (Author)

Designed for quick, easy comprehension, this handbook reference will assist medical students in understanding the rationale behind antibiotic selection for common bacterial pathogens and infectious disease presentations. By supplying the rationale for choosing antibiotics, the book reduces the amount of memorization necessary for proper antibiotic prescribing. The book is heavily illustrated with two-color figures and includes fact-anecdotes, interesting ancillary information, mnemonics, and questions to test understanding. Appendices include dosing in adults and children; antibacterial agents in pregnancy; generic and trade names of commonly used antibacterial agents; and treatment of infections caused by bacterial agents of bioterrorism.

Fish Cycline (Tetracycline 250 mg) - 100 Caps

Fish Cycline (Tetracycline 250 mg) - 100 Caps
by THOMAS LABS

Non-prescription tetracycline labeled for fish or aquarium use for the control of common bacterial infections. Each capsule contains 250 mg tetracycline. Directions: Add contents of capsule to aquarium water at the rate of 1 per 10 gals. Repeat in 24 hours. Continue treatment for 5-10 days.

Neosporin Plus Pain Relief First Aid Antibiotic/Pain Relieving Ointment, Maximum Strength, 1-Ounce Tubes (Pack of 3)

Neosporin Plus Pain Relief First Aid Antibiotic/Pain Relieving Ointment, Maximum Strength, 1-Ounce Tubes (Pack of 3)
by Neosporin

Bacitracin Zinc-Neomycin Sulfate-Polymyxin B Sulfate-Pramoxine HCI. Maximum Strength Pain Relief. Soothes painful cuts, scrapes and burns while preventing infection. Keep In: Kitchen; Bathroom; Workshop; Travel Bag. Soothes the pain of burns; Suitable for

© 2009 BrightSurf.com