Researchers have discovered a protein action in a lung-favouring bacteria that has helped them understand its resistance to the body’s immune system.
Microbiologists at Queen’s University Belfast have made a breakthrough in bacteria research which could lead to the development of new treatments for people with compromised immune systems, such as those with cystic fibrosis.
Cystic fibrosis is an inherited condition that primarily affects the lungs and digestive system. Ireland has the highest incidence of the disease per population in the world, with three times the rate of the EU and the US. Though a very serious condition, there have been huge advances in treatment, including new drug therapies to tackle the underlying causes of the disease.
In a paper published in the latest issue of Cell Reports, researchers detailed how the bacterium Achromobacter, which can cause chronic lung infection and tissue damage in the airways, overcomes the body’s immune defences to multiply and grow.
“Achromobacter bacteria can cause chronic and potentially severe infections. However, until now, how this opportunistic bacterium interacts with the human immune system has been poorly understood,” said Prof Miguel A Valvano, chair in microbiology and infectious diseases at the Wellcome-Wolfson Institute for Experimental Medicine at Queen’s University Belfast and lead researcher on the study.
“These bacteria resist the action of multiple antibiotics; therefore, infection by these microorganisms is very difficult to treat by conventional therapies, especially in people living with cystic fibrosis or other immunocompromising conditions, such as patients on chemotherapy,” Valvano explained.
In studying Achromobacter, the research team found that this type of bacteria can survive within the body’s immune cells using a specialised protein complex, called the type 3 secretion system, which deploys molecules that induce the immune cells to self-destruct. As immune cells die off, more are recruited to fight the invading pathogen.
However, immune cells deficient in two inflammation sensors, NLRC4 and NLRP3, do not die, suggesting that these two sensors are required for the recognition of the pathogen.
The researchers observed that Achromobacter infection leads to damage in lung structure and causes severe illness if the specialised secretory pathway is functional, but not if bacteria carry mutations in the secretion system.
This demonstrates that the immune cells’ self-destruct alarm is triggered by the type 3 secretory system pathway but that this inflammatory response is insufficient for the immune system to defeat the bacteria.
The next step for the researchers is to determine whether Achromobacter has any other proteins that help it survive and invade other cell types in the body.
Knowledge of the type 3 secretion system and other proteins could be useful for developing novel treatments against this dangerous pathogen.
The team in Queen’s University collaborated with colleagues in the University of Cambridge and the University of Sharjah to conduct the study, which was funded by the US Cystic Fibrosis Foundation.
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