Tag: shigella

How Shigella Suppresses the Immune System

Anatomy of the gut
Source: Pixabay CC0

Researchers report in the journal Cell on insights they have made into the molecular process by which bacteria such as the highly contagious Shigella suppresses the immune system, preventing it from recognising impending infection.

Interferons are the first line of the immune system’s defence against infection. These warn neighbouring cells and prepare them to fight off an incoming infection. Many viruses – including SARS-CoV2 – have evolved proteins which inhibit normal interferon functions in order to increase infectivity.

Whether bacteria such as Shigella, which causes dysentery, are also able to interfere with the immune system and its capacity to fight the infection was previously unknown. Shigella is highly contagious, requiring only a small inoculum (10 to 200 organisms) to cause an infection.

The study found that Shigella inject a protein called “OspCs” into cells, which blocks the host’s interferon response, allowing the bacteria to successfully infect the host.

Interestingly, OspCs blocked interferon signalling by preventing cells from adapting to changing concentrations of calcium – a molecular signal that usually alerts a cell to infection and damage.

This newly identified strategy tricks the immune system, preventing the body from mounting an effective immune response to infection by decoding host calcium signals.

“This study was another perfect example of how studying pathogens can not only lead to a better understanding of infectious processes, but can also reveal the complexity of host responses to infection,” said Dr Charlotte Odendall.

These findings may be the first steps towards new bacterial treatments in the future, the researchers said.

Source: Kings College London

How Shigella Bacteria Hijacks Cells

Shigella bacteria Credit: S Bhimji, MD

Shigella, a bacterial pathogen that causes dysentery and is the leading cause of childhood diarrhoeal diseases, inserts a pore called a translocon into an infected person’s intestinal cells and then injects bacterial proteins into the cells. Once inside, the proteins hijack the cellular machinery to help Shigella multiply. In a study published in mBio, researchers report important details about Shigella’s translocon, which may help researchers develop an effective strategy to block this critical component of infection.

“Shigella infects our gut by manipulating our intestinal cells and tricking them into letting the Shigella inside. In fact, there are many bacterial pathogens that use this same, or similar, mechanism to infect us,” said lead author Poyin Chen, PhD, a postdoctoral fellow at MGH. “This translocon pore is essentially the gateway through which bacterial proteins get pumped into our cells. We know that this structure is made of two proteins – IpaB and IpaC – but what we don’t know is how these proteins fit together to make this pore.”

Using protein mapping techniques to look closely at translocons when they were embedded in cell membranes, the researchers were able to see that ipaB makes up the inner ring of the pore. “If you think of the translocon pore as a donut, this would be the walls of the donut hole. This finding is important because this is the part of the translocon pore that directly interacts with bacterial proteins as they are injected into our cells,” Dr Chen explained. “With the findings from this study, we can begin to understand if this pore acts as a slippery tube that bacterial proteins travel through or if the translocon pore can control the flow of bacterial proteins into our cells.”

Such details may help investigators target the translocon and block the entry of Shigella proteins into cells. “For something that is so essential to establishing infection, we know terribly little of how it’s made and how it works,” said Dr Chen. “As we gain a better understanding of its parts, we will be able to approach the structure as a whole and maybe even find ways to neutralise the function of this structure to prevent infection before it can begin.”

Source: Massachusetts General Hospital