Study suggests that antibiotics may help fight norovirus

Antibiotics aren't supposed to be effective against viruses. But new evidence in mice suggests antibiotics may help fight norovirus, a highly contagious gastrointestinal virus, report scientists at Washington University School of Medicine in St. Louis.

The researchers found antibiotics could help prevent norovirus infections. The same team also showed that a recently identified immune system molecule can cure persistent norovirus infections even in mice with partially disabled immune systems. The surprising findings, available online in Science, will appear Jan. 16 in the journal's print edition.

Outbreaks of norovirus are notoriously difficult to contain and can spread quickly on cruise ships and in schools, nursing homes and other closed spaces.

The researchers found that norovirus works its way into gut tissue in mice that have been pretreated with antibiotics but that the virus cannot establish a persistent infection. Follow-up studies showed that norovirus needs a bacterial collaborator to establish a persistent infection in the gut. Eradicating the bacterial partner with an antibiotic can prevent persistent norovirus infection in mice.

"The virus actually requires the bacteria to create a persistent infection," said senior author Herbert W. Virgin IV, MD, PhD, the Edward Mallinckrodt Professor of Pathology and head of the Department of Pathology and Immunology. "The virus appears to have a symbiotic relationship with the bacteria they share the job of establishing persistence."

Study suggests that antibiotics may help fight norovirus

Bacteria beware: Researchers have a natural sidekick that may resolve the antibiotic-resistant bacteria dilemma

Mice infected with Escherichia coli (E. coli) or Staphylococcus aureus(S. aureus) bacteria were given molecules called specialized pro-resolving mediators (SPMs) along with antibiotics. SPMs are naturally found in our bodies, and are responsible for mediating anti-inflammatory responses and resolve inflammation. An anti-inflammatory response is the body's attempt to protect itself from infectious agents and initiate the healing process.

The researchers found that specific types of SPM molecules, called resolvins and protectins, were key in the anti-inflammatory response to limit tissue damage by stimulating the body's white blood cells to contain, kill and clear the bacteria.

Administered with antibiotics, resolvins and protectins heightened immune response by commanding white blood cells to attack and engulf the bacteria, thereby quickly reducing the amount of bacteria in the blood and tissues.

RvD5-a type of resolvin-in particular was also helpful in regulating fever caused by E.coli, as well as counter-regulating genes responsible for mounting excess inflammation associated with infections; hence, limiting the collateral damage to the body while fighting infection.

Serhan and colleagues are the first to demonstrate RvD5, as well as its actions against bacterial invasion. The BWH team, collaborating with Fredrik Bäckhed, PhD of the Sahlgrenska Center for Cardiovascular and Metabolic Research in Sweden, found that germ-free animals produce high levels of resolvins.

Ref : http://www.nature.com/nature/journal/v484/n7395/full/nature11042.html

Bacteria beware: Researchers have a natural sidekick that may resolve the antibiotic-resistant bacteria dilemma

Mystery of Bacterial Growth and Resistance Resolved ?

In continuation of my update on the mechanism of bacterial resistance...

Scientists at The Scripps Research Institute have unraveled a complex chemical pathway that enables bacteria to form clusters called biofilms. Such improved understanding might eventually aid the development of new treatments targeting biofilms, which are involved in a wide variety of human infections and help bacteria resist antibiotics. 

Biofilm formation is a critical phenomenon that occurs when bacterial cells adhere to each other and to surfaces, at times as part of their growth stage and at other times to gird against attack. In such aggregations, cells on the outside of a biofilm might still be susceptible to natural or pharmaceutical antibiotics, but the interior cells are relatively protected. This can make them difficult to kill using conventional treatments.

Past research had also revealed that nitric oxide is involved in influencing bacterial biofilm formation. Nitric oxide in sufficient quantity is toxic to bacteria, so it's logical that nitric oxide would trigger bacteria to enter the safety huddle of a biofilm. But nobody knew precisely how. In the new study, the scientists set out to find what happens after the nitric oxide trigger is pulled. "The whole project was really a detective story in a way," said Plate.

To learn more, the researchers used a technique called phosphotransfer profiling. This involved activating the histidine kinase and then allowing them to react separately with about 20 potential targets. Those targets that the histidine kinase rapidly transferred phosphates to had to be part of the signaling pathway.

"It's a neat method that we used to get an answer that was in fact very surprising," said Plate. 

The experiments revealed that the histidine kinase phosphorylated three proteins called response regulators that work together to control biofilm formation for the project's primary study species, the bacterium Shewanella oneidensis, which is found in lake sediments.

Further work showed that each regulator plays a complementary role, making for an unusually complex system. One regulator activates gene expression, another controls the activity of an enzyme producing cyclic diguanosine monophosphate, an important bacterial messenger molecule that is critical in biofilm formation, and the third tunes the degree of activity of the second.

Since other bacterial species use the same chemical pathway uncovered in this study, the findings pave the way to further explore the potential for pharmaceutical application. As one example, researchers might be able to block biofilm formation with chemicals that interrupt the activity of one of the components of this nitric oxide cascade.

Ref : http://www.scripps.edu/news/press/2012/20120426marletta.html

http://www.sciencedirect.com/science/article/pii/S1097276512002602