New clues point to why bacteria can turn lethal and cause meningitis


Researchers have found a clue as to why bacteria that often live harmlessly in the back of the nose and throat can turn lethal and cause meningitis.

New research helps shed light on the genes responsible for a shield-like capsule that could help protect some bacteria from our immune system.

Scientists compared the genetic code from thousands of samples and found differences in the cellular machinery responsible for producing this bacterium’s capsule coating.

They identified specific subtle genetic changes which produced shield-like hypercapsulation surrounding the bacterium that could improve its survival against our immune system.

The research, published in the journal Lancet Microbe, found the presence of this hypercapsulation was almost twice as high among the bacteria which caused serious diseases compared to the bacteria which was harmlessly carried.

Researchers say the findings could help produce rapid tests to identify the risk of severe infection.

Dr Edmund Loh, Karolinska University Hospital, who led the study, said: “We found genetic changes which altered a biological regulator called RNAT.

“These changes produced more protective capsule around the bacteria.

“This hypercapsulation could help them evade the human immune response and become deadly.

“In some samples, the genomes of deadly bacteria were almost identical to harmless ones, except for a notable difference in the RNAT.”

Neisseria meningitidis (meningococcal bacteria) is a leading cause of meningitis.

As many as one in 10 people carry the bacteria harmlessly in the back of the nose and throat, but they can occasionally turn lethal.

The mechanisms of how these bacteria shift to causing severe infection have not been very well understood.

The new research compared the genes of the cellular machinery responsible for producing the bacterium’s outer shell – the capsule.

This is a large structure made of complex sugars that forms part of the outer envelope of a bacterial cell.

It is one of the bacteria’s main defences against the human immune system.

The researchers found that some bacteria produced more capsule than others – hypercapsulation – which acts as a shield against our immune system.

They also found that increased capsule production was associated with higher survival rates in human blood serum.

A temperature-sensitive molecule called an RNA thermosensor (RNAT) controls the production of this capsule.

In the study researchers compared more than 7000 samples of meningococcal bacteria looking at differences in these RNATs.

They discovered five new variations of this RNAT which led to hypercapsulation, and so better protection inside the human body.

The prevalence of these variant RNATs was almost twice as high in bacteria that cause diseases compared with ones that are harmlessly carried.

Dr Loh added: “We are now working on a simple and quick test that could help identify these changes to the RNAT and spot outbreaks of serious infection that can lead to meningitis.”

The study used whole-genome sequences from samples freely available from the Meningitis Research Foundation (MRF) Meningococcal Genome Library, developed by Public Health England, the Wellcome Trust Sanger Institute, and the University of Oxford as a project funded by MRF.