Lactate Triggers Invasion of Meningitis-Causing Bacteria into Blood

Highlights:

Lactate is an important substrate for energy, especially for cardiac output.
When it is present in the upper respiratory tract, it leads to detachment of colonies of meningitis-causing bacteria.
The detached bacteria enter the blood stream, leading to severe infection.

Lactate is a byproduct of glucose metabolism and it is used as a substrate for energy production during exercise. However, a research team from Stockholm University in Sweden has found that lactate produced in the upper throat, could lead to the detachment of small colonies of meningitis-causing bacteria, resulting in the spread of the bacteria to the rest of body due to invasion into the blood. This study, published in PLOS Pathogens, describes the colonization of the bacterium Neisseria meningitides in the upper respiratory tract.

The bacterium Neisseria meningitides is found in the upper respiratory tract in 10 to 35% of people in the upper respiratory tract but it is harmless, in most instances. Sometimes, this bacterium could invade the body and lead to infection, called meningitis.

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Meninges are the three layers of membrane that cover the brain and infection of the cerebrospinal fluid between them causes meningitis the disease of the meninges.

‘Lactate is a substrate for energy and is found to trigger an invasion of the meningitis-causing bacteria into the blood.’

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Mechanism of Infection

The process of infection follows a two-step process:

Colonies of the bacteria first begin to develop in the upper throat
These colonies disperse and invade the lining of the mucosa, entering the blood stream

The second step, the process of dispersal is not well understood. Dr. Sara Sigurlásdóttir and colleagues tried to analyze if the dispersal of the colonies of N.meningitides was triggered by any function or substance produced by the body.

The initial studies carried out by the scientists, using live cell imaging, showed that N. meningitidis microcolonies did not need to have a direct association with human cells. Instead, just being present among a group of cells that contained human cells is trigger enough for them to be dispersed.

Identifying the Specific Trigger

There were further studies that were conducted to identify the exact molecule that acted as the trigger. The scientists found that the dispersal of the meningitis-causing microcolonies was associated with the presence of the substrate lactate. The main function of lactate was found to be that of a signaling molecule as it was not metabolized by N. meninitidis.

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The pathway of meningitis infection has never been detailed and this study attempts to find an association between lactate as a trigger and the dispersal of these microcolonies. The exact role of lactate has not been identified thus far, but it could be a critical step in analyzing how a seemingly common and harmless micro-organism colony could be dispersed and result in infection.

Dr. Ann-Beth Jonsson, a professor at Stockholm, said that the mechanism of action of lactate as a signaling molecule was intriguing and that the vital steps unveiled will help in preventing as well as treating meningococcal disease.

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Significance of Lactate in the Body

Increased glucose metabolism occurs on exercising the skeletal muscle; however, in the case of cardio or heart exercise, there is an increase in glucose metabolism initially, which comes back to the decreased levels that are present during rest after the start of high intensity exercise. There was a significant increase in serum lactate after high intensity exercises, which leads us to conclude that lactate as opposed to glucose is utilized for cardiac energy production.

Bacterial Meningitis

Bacterial meningitis caused by Neisseria meningitides is a serious condition and could become life threatening. It is characterized by a swelling or an inflammation of the layer surrounding the brain, the meninges. The infection of the fluid around the brain leads to the inflammation. Since there are other bacteria and viruses which can cause meningitis, it is important to identify the cause so that specific treatment may be provided.

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The tests that are conducted to reveal the cause of meningitis take several days to weeks, by which time precious time may be wasted. To overcome this situation, scientists identified a new biomarker for bacterial meningitis.

In a study titled “Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children” by Eduardo Mekitarian Filho and colleagues, published in the International Journal of Emergency Medicine, the effectiveness of cerebrospinal level of lactate was used as a diagnostic marker. It is used to identify if the meningitis is caused by bacteria.

It was found that the cerebrospinal fluid consisted of high lactate levels among children who had meningitis. This was because

Bacteria produced lactate due to anaerobic metabolism
Lactate was also produced by ischemic brain tissue

The ability to distinguish bacterial meningitis from other types of meningitis was found to be possible using lactate levels in the cerebrospinal fluid.

The current study that identifies the concentration of lactate as a key factor in the dispersal of colonies of N.menigitidis could be used as a means to understand the mechanism of disease progression and can also be used as a new target for drug therapy against this potentially life threatening infection.

References:

Sara Sigurlásdóttir et al. Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal. PLOS Pathogens, April 2017 DOI: 10.1371/journal.ppat.1006251
Lactate – the forgotten fuel! - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2290415/)
Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996047/)

Source-Medindia