Staphylococcus aureus strains such as MRSA prefer human blood to that of other mammals because they bind best to human hemoglobin, the oxygen-carrying protein that contains the iron they need to survive, said US researchers who also suggested genetic variations in hemoglobin may explain why some people are more susceptible to Staph infections than others.
Having found the Staph receptor for hemoglobin in previous studies, in their latest study, published today in Cell Host & Microbe, senior author Dr Eric Skaar from Vanderbilt University Medical School in Nashville, Tennessee, and colleagues found it has increased affinity to human hemoglobin than to that of other animals.
Skaar, who is associate professor of Microbiology and Immunology, said in a statement that Staph, which needs the iron hidden red blood cells to grow and cause infections, lives in the noses of about 30 per cent of all people, yet:
“A big question in Staph biology is: why do some people continuously get infected, or suffer very serious Staph infections, while other people do not?”
“Variations in hemoglobin could contribute,” he said.
Staph is a significant threat to human health throughout the world. It is the leading cause of soft tissue and pus-forming skin infections, the leading cause of infectious heart disease, one of the four leading causes of foodborne infections, and the number 1 hospital-acquired infection.
A cause for concern is that antibiotic-resistant strains of S. aureus, the so-called “Superbugs” like Methicillin-resistant Staphylococcus aureus (MRSA), are on the rise in hospitals and communities.
The thought that “complete and total antibiotic resistance of the organism is inevitable at this point,” spurred Skaar and his team to look for new antibiotic targets, which is how they came to focus on Staph’s nutritional requirements.
They are hoping to find a way to “starve” the organism of the metals, like iron, that it needs to grow and multiply.
To steal iron from red blood cells, S. aureus pops them open, binds the hemoglobin to its own cell wall, extracts the heme, the compound that contains the iron, passes it through the cell wall, and then degrades it to release the iron.
In previous studies, Skaar and colleagues identified the bug’s hemoglobin receptor, a protein called IsdB, which helps it to dock the hemoglobin molecule to itself.
In this study, Skaar and colleagues found that:
“Increased specificity for human hemoglobin (hHb) translates into an improved ability to acquire iron and is entirely dependent on the staphylococcal hemoglobin receptor IsdB.”
To arrive at this finding they studied Staph’s ability to infect mice expressing human hemoglobin. They found these “humanized” mice were more susceptible to systemic Staph infection compared to control mice.
They also studied the hemoglobin-binding preferences of other pathogenic bacteria and found those that exclusively infect humans, such as the one that causes diphtheria, prefer human hemoglobin to that of other animals.
This was in contrast to pathogenic bacteria that also infect other animals, such as Pseudomonas and Bacillus anthracis (the cause of anthrax), they “didn’t exhibit a hemoglobin preference,” said Skaar.
Skaar said the mouse model they used in this study will be a valuable research tool because Staph infects them in a way that more closely resembles the infectious process in humans. They hope also to find out if these mice will be a useful model for studying other types of infection.
The researchers concluded that:
“These results suggest a step in the evolution of S. aureus to better colonize the human host and establish hHb-expressing mice as a model of S. aureus pathogenesis.”
If variations in hemoglobin are the reason that some people become infected while others do not, it might be possible to identify patients who are more susceptible and treat them before they come into hospital for surgery or other procedures. Skaar and colleagues plan to explore this using Vanderbilt’s DNA Databank, BioVU.
They also plan to continue investigating the molecular interaction between hemoglobin and the IsdB receptor to find a way of disrupting it for use in new antibiotics.
“Specificity for Human Hemoglobin Enhances Staphylococcus aureus Infection.”
Gleb Pishchany, Amanda L. McCoy, Victor J. Torres, Jens C. Krause, James E. Crowe, Mary E. Fabry, Eric P. Skaar.
DOI: 10.1016/j.chom.2010.11.002
Additional source: Vanderbilt University Medical Center.
Written by: Catharine Paddock, PhD