Calcium Induces Switch from Acute to Chronic Lung Infection

Highlights

• Pseudomonas aeruginosa causes 10% of all nosocomial infections, in particular pneumonia
• Role of calcium in Pseudomonas aeruginosa bacterium identified 
• Cystic fibrosis patients harbor calcium sensitive bacteria

University of Basel's Biozentrum researchers have identified that calcium induces chronic lung infections. Scientists have reported in the Nature Microbiology why antibiotics are less effective in fighting Pseudomonas aeruginosa in its chronic state. Pseudomonas aeruginosa is one of the most serious pathogens which causes hospital infections and difficult to treat owing to its multi-resistance to antibiotics. Pseudomonas aeruginosa is the leading cause of chronic lung infections in immune-compromised patients

In early and acute stages of pneumonia, the pathogen uses virulence factors to invade the host and evade its immune system. During the disease progression, the bacterium changes its game by switching from acute to chronic virulence.

This switching process halts the production of the virulence factors and instead results in the formation of a protective matrix which reduces its growth rate. Until now the environmental signals that direct this transition was unknown.

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

Researchers have now identified that a receptor located in the bacterial cell envelope monitors the calcium concentration in the environment and transmits this signal into the cell.

Higher calcium levels trigger the switch to a chronic program: The bacterium protects itself with the matrix like structure, reduces its growth rate and thereby increase the drug tolerance and persistence.

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Patients suffering from cystic fibrosis develop lifelong chronic infections by P. aeruginosa, which permanently damage their lung tissue. "Most of the isolates from airways of CF patients have retained their calcium sensitivity," emphasizes Jenal. "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."

Source-Medindia