Calcium May Play a Role in Chronic Lung Infections

Recent findings suggest that calcium may play a role in the switch from acute to chronic lung infection from the bacterium Pseudomonas aeruginosa.

This bacterium is commonly found in hospitals, and can cause life-threatening infections that are hard to treat due to antibiotic resistance. It is responsible for approximately 10% of hospital-acquired infections, including pneumonia.

The bacteria can cause infections such as pneumonia, septic shock, urinary tract infections, gastrointestinal infections, as well as skin and soft tissue infections. Immunocompromised patients are most at risk, including those with cystic fibrosis, neutropenia, infants, and patients with burns or wound infections.

In acute stages of pneumonia, P aeruginosa uses virulence factors to spread throughout the body while evading the immune system. As the disease progresses, the bacteria switches to chronic virulence and stops producing virulence factors, which creates a protective matrix. During this time, it also limits its growth.

The mechanisms behind the switching between acute and chronic infection were previously unknown, but investigators in the study published by Nature Biology discovered that calcium triggers the switch.

“In Pseudomonas a central signaling pathway senses environmental information and ultimately determines whether the pathogen will undergo the acute to chronic virulence switch,” said lead researcher Urs Jenal, PhD. “Although the components of this pathway are well-known, none of the external signals modulating the switch are defined.”

The investigators have found a receptor located in the bacterial cell envelope monitors calcium concentration and transmits the signal into the cell, as elevated levels trigger the switch.

Through the switch, the bacteria are able to protect itself with a biofilm structure and reduces the growth rate, which results in drug resistance.

Investigators were able to test their findings in patients with cystic fibrosis who develop chronic infections from P aeruginosa. Since patients with cystic fibrosis (CF) have irregular calcium levels, regulation may help treat these patients, and prevent long-term lung damage associated with the infection.

“Most of the isolates from airways of CF patients have retained their calcium sensitivity,” Dr Jenal concluded. “We believe that this allows these bacteria to constantly adapt their virulence in response to the often changing conditions in the airways. One of the characteristics of cystic fibrosis is deregulated calcium homeostasis. We assume that elevated calcium levels in patients promote the switch from an acute to a chronic state of infection. This is of advantage for the pathogen, as it may ensure its long-term survival in the respiratory tract. At the same time, treatment of chronically infected patients becomes more challenging.”