Scientists identify how meningitis bacteria invade the brain

Washington, Aug 19 (ANI): Scientists in the U.S. have discovered that a specific protein on the surface of a common bacterial pathogen allows the bacteria to leave the bloodstream and enter the brain, initiating the deadly infection known as meningitis.

The new finding may lead to the development of improved vaccines to protect those most vulnerable, including young infants and the elderly.

“Streptococcus pneumoniae, commonly known as pneumococcus, is responsible for half the cases of bacterial meningitis in humans,” said the study’s senior author, Victor Nizet, MD, professor of paediatrics and pharmacy at the University of California, San Diego’s School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences.

Meningitis develops when bacteria penetrate the “blood-brain barrier.”

The blood-brain barrier, comprised of a single layer of highly specialized microvascular endothelial cells, prevents most large molecules from entering into the cerebrospinal fluid, preserving an optimal biochemical environment for brain function.

The research team examined the functions of a protein known as NanA in order to discover how an entire bacterium can breech the blood-brain barrier and gain access to the central nervous system.

NanA is produced by all strains of pneumococcus and displayed prominently on the bacteria’s outer surface.

Through genetic manipulations, the researchers were able to remove the entire NanA protein, or just specific sections of the molecule, from the pathogen.

They found that while normal pneumococci were able to bind, enter and penetrate through human brain microvascular endothelial cells, mutant bacteria lacking the NanA protein -or those expressing only a truncated version of the protein – largely lost these abilities.

Conversely, when the full-length pneumococcal NanA protein was cloned and expressed on the surface of a nonpathogenic laboratory strain, the transformed bacteria gained the ability to bind and enter the same endothelial cells.

Satoshi Uchiyama, MD, a postdoctoral fellow in the Nizet Laboratory and lead author on the study, said: “Our tissue culture studies showed that the NanA protein was both necessary and sufficient for bacterial penetration of the blood brain barrier endothelial cells.”

“After infecting mice intravenously, we also found that far fewer NanA-deficient bacteria left the bloodstream and entered the brain, in comparison to mice infected with the normal pneumococcus,” Uchiyama added.

NanA is best known as an enzyme that cleaves and releases the sugar molecule known as sialic acid, which is present in abundance on the surface of all human cells.

While this enzymatic activity played a small part in promoting NanA-mediated blood-brain barrier interactions, a much stronger role was identified for the outer tip of the protein.

This tip seems to directly attach to the brain microvascular endothelial cells and then stimulate them to take in the pneumococcus.

According to Nizet, because NanA is expressed on the surface of all pneumococcal strains, it is an attractive candidate to include in a universal protein-based vaccine against pneumococcal infection.

The study is available online in the Journal of Experimental Medicine. (ANI)

Paediatric vaccine found effective in preventing pneumococcal meningitis

London, Jan 15 (ANI): A standard paediatric vaccine for preventing common life-threatening infections can also be effective against pneumococcal meningitis in both children and adults, say researchers.

Pneumococcal meningitis is an infection in the brain and spinal cord membranes caused by the pneumococcus – a bacterium that also causes pneumonia and other serious infections.

While reviewing 1,379 cases of pneumococcal meningitis from 1998 through 2005, study authors found rates of the disease decreased in children and adults after the introduction of pediatric pneumococcal conjugate vaccine (PCV7) in 2000.

PCV7 protects against seven of the most common pneumococcal types, which account for over 80 percent of pneumococcal disease in young children.

The incidence rates for pneumococcal meningitis in all age groups declined 30.1 percent from 1998-1999 to 2004-2005.

After PCV7 was made available, the incidence of meningitis decreased by 64 percent in children, and by 54 percent in older adults.

“When you immunize children, they are much less likely to carry pneumococcal strains covered by the vaccine in the back of the throat,” New England Journal of Medicine quoted Dr. Lee Harrison, senior author of the study and professor of medicine, University of Pittsburgh School of Medicine.

“When vaccinated children don’t carry these virulent strains, they don’t end up transmitting them to other children, their parents and grandparents.

“PCV7 has been highly successful in preventing pneumococcal meningitis, but it remains a very serious and deadly disease,” he added. (ANI)

Salmonella-based vaccine candidates can help fight infant pneumonia

Washington, January 13 (ANI): Scientists at Arizona State University’s Biodesign Institute have come up with two vaccine candidates that may prove very helpful in dealing with infant bacterial pneumonia.

Research leader Roy Curtiss, an investigator of vaccines and infectious diseases, has revealed that the two vaccine strains draw on the properties of an unlikely vaccine carrier-one generally associated with causing sickness rather than safeguarding the body against it.

Salmonella typhimurium, a rod-shaped motile pathogen, is one of over 2000 strains or serotypes of the Salmonella constellation of bacteria, which are responsible for causing serious and oft-fatal diseases to which children under two years of age are particularly vulnerable.

Due to this fact, Salmonella’s choice as the principal component in a new vaccine for babies has been something of a hard sell.

“People said ‘you gotta be kidding,’” says Curtiss, noting that twenty years ago, Salmonella outbreaks were a grave concern in nurseries and hospitals, sometimes leading to the deaths of over half the children in such facilities.

Now, Curtiss and lead author Yuhua Li have led the development of two new vaccine candidates, labeled x9088 and x9558, under grants from the NIH and the Bill and Melinda Gates Foundation.

The researchers say that the novel strains belong to a family known as recombinant attenuated Salmonella vaccines (RASVs). They say that the critical component boosting their effectiveness is a delayed mechanism of attenuation.

According to them, Salmonella’s notorious virulence is essentially short-circuited, but only after it has stimulated a robust systemic immune response to pneumococcal surface protein A (PspA), a vital bacterial pneumonia antigen.

The researchers say that this feat is achieved by using genetic trickery to tame S. typhimurium, producing altered bacterial strains requiring mannose and/or arabinose-sugars available in the lab, but absent in the human body.

After roughly seven cell divisions, the bacterium exhausts its stores of specialized sugar. Unable to sustain the integrity of its cell wall, it bursts.

This approach can help place Salmonella on a self-destruct timer, one that may be sensitively tuned to achieve maximum immunogenicity following colonization of host tissues.

Describing the technique in PNAS, the researchers revealed that an initial version of the new vaccine is soon to begin the first pre-clinical trials in human subjects. (ANI)

No evidence to show that pneumococcal protects against pneumonia

Washington, Jan 6 (ANI): Researchers from Switzerland and the UK have found that commonly used pneumococcal polysaccharide vaccines (PPVs) do not seem to be effective for preventing pneumonia.

In many industrialized countries, PPVs are currently recommended to help prevent pneumococcal disease in people aged 65 and over and for younger people with increased risk due to conditions like HIV.

Previous studies have shown conflicting results regarding the efficacy of PPV.

The new findings are based on a study, which looked at 22 clinical trials, reviews and meta-analyses and more than 100,000 participants from countries in North America as well as India, Africa, Latin America and the Caribbean.

Unlike other similar studies, the researchers examined the reasons why different clinical trials produced different results.

They found that the quality of the studies substantially affected the results.

When only high quality trials were included, there was no evidence that PPVs could prevent pneumonia.

The new study contributes to the ongoing debate around effectiveness of the vaccine.

“Policy makers may therefore wish to reconsider their current recommendations for PPV, especially where routine pneumococcal conjugate immunization has been introduced,” said Dr. Matthias Egger from the University of Bern, Switzerland and co-authors. (ANI)