Living within the bones
HZI research uncovers the survival secrets of osteomyelitis-causing Staphylococcus aureus
Osteomyelitis is an infection of the bone that is generally associated with high levels of bone marrow inflammation and bone destruction. Scientists of the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, reported how the pathogen Staphylococcus aureus, which is the main causing agent of this disease, adapts to the life inside the bone and how this pathogen evades the killing activity of the immune system. Published in the scientific journal mBio, their findings open up important new avenues for the treatment of this tedious and cost-intensive bone infection.
The current treatment of Osteomyelitis is difficult. Despite long and high dose antibiotic treatment, the rate of clinical failure in osteomyelitis treatment is very high, and frequently results in extremity amputation. After entering the bone, Staphylococcus aureus first cause an acute infection in this location. "The first symptoms usually include no more than fever and a general feeling of fatigue, which subsides after some time," says Prof Eva Medina, head of the Infection Immunology research group of the HZI. "But the infection often becomes chronic and reoccurs despite intensive antibiotic treatment. The consequences can be severe and include bone deformation with an increasing risk of bone fracture." Especially people with weakened immune system or those afflicted by another chronic disease such as diabetes, to name just one example, are at risk.
Chronic staphylococcal osteomyelitis remains a challenging medical problem because the bacterial pathogen residing inside the bone is well-protected from the killing effect of antibiotics and other medications. In addition, the pathogen utilizes a number of strategies to escape the human defence mechanisms and to survive inside of the bones despite the scarcity of food in this anatomic location. Medina and her colleagues were the first to report the life style of Staphylococcus aureus during osteomyelitis and how the bacterial life style changes between the acute and the chronic phases of infection. "During the acute phase, food is available within the bones and the pathogen multiplies. During the chronic phase, when most of the food has been consumed, the pathogen shuts down its metabolism. It basically goes into hibernation and just survives, without proliferating" says Medina. "This strategy allows Staphylococcus aureus to persist for long periods inside of the bone in extreme scarcity of food supplies."
The scientists also showed that the pathogen produces an enormous amount of proteases during the infection of the bone. These enzymes cleave proteins, for example structural proteins of the bone. "The increased production of these enzymes indicates that Staphylococcus aureus obtains its food directly from the bone. It basically eats up the bone from inside," says Medina. As a result, the bone becomes deformed and porous and breaks easily.
The researchers also unravelled an additional mechanism that allows the bacteria to escape the immune system and survive within the bones. "Following infection, the pathogen increasingly produces toxins that kill neutrophilic granulocytes," says Medina. Neutrophilic granulocytes are white blood cells that play a major role in the non-specific defence against infections. This means that Staphylococcus aureus does not hide from the human immune system, but rather engages itself in an active battle against the body's defence mechanisms.
"Now that we know the survival mechanisms of this pathogen during bone infection, we can develop specific strategies aimed to interrupt or prevent these mechanisms," says Medina. "In the long run, this is a very important step to achieve a better control of staphylococcal osteomyelitis in the future."
Citation Szafranska AK, Oxley APA, Chaves-Morenob D, Horsta SA, Roßlenbroich S, Peters G, Goldmann O, Rohde M, Sinha B, Pieper DH, Löffler B, Jauregui R, Wos-Oxley ML, Medina E. 2014. High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis. DOI:10.1128/mBio.01775-14.