Researchers Find Specific Protein Responsible for Some Antibiotic Tolerance

A paper published in the Proceedings in the National Academy of Sciences pinpointed a “specific protein within our immune system that interferes with [an] antibiotic’s ability to kill bacteria.”

Beta-lactam antibiotics, which are “commonly used to treat various bacterial infections, from urinary tract infections to pneumonia and sepsis,” can sometimes fail, even without antibiotic resistance. The UNC professor who was senior author on the paper found that a “major innate immune protein sequesters essential metals, which can inadvertently allow the bacteria to survive our most widely used antibiotic class.”

Antibiotic tolerance can lead to bacteria withstanding “strong doses of antibiotics.” For instance, “about 20% of patients with MSSA (methicillin sensitive Staphylococcus aureus) infections treated with oxacillin die. These outcomes are tied to antibiotic tolerance, where pathogens are able to survive the killing activity of the antibiotic for extended periods.”

Researchers focused on calprotectin, a “powerful protein within our immune system that serves as one of the body’s ‘first responders’ at infection site(s).” They found that the protein “starves Staph cells of zinc and manganese, essential metals that the bacterial cells need to survive and grow. But when they exposed cellular models with calprotectin to an antibiotic called cefazolin, they made a staggering finding: the antibiotic no longer killed the bacteria. Something was preventing antibiotics from doing their job.” This suggests that antibiotic tolerance stems from an “individual’s own immune system, rather than a pathogen alone.”