How antibiotics may worsen drug-resistant bacterial infections

How antibiotics may worsen drug-resistant bacterial infections

In recent decades, methicillin-resistant Staphylococcus aureus, or MRSA, has evolved from a controllable nuisance into a serious public health concern. A pre-clinical study published in Cell Host & Microbe now reveals that treatment with first-line antibiotics may actually make MRSA skin infections worse, ironically by activating the body's own pathogen-defense system. 

Beta-lactam antibiotics kill many bacteria by inactivating proteins involved in cell wall synthesis. But MRSA bypasses the drug's actions by stimulating a gene called mecA, which in turn activates a back-up pathway for cell wall synthesis. This genetic change allows MRSA to survive antibiotics, but at the same time it alters the structure of the bacterial cell wall.

In the new study, the researchers tested whether the immune system responds to these structural changes in a way that worsens MRSA infections. They found that exposure of MRSA to beta-lactam antibiotics induced mecA activation, which weakened the chemical bonds between molecules in the cell wall and rendered the bacteria more easily degradable by immune cells. The degradation of the cell wall released fragments that were recognized by the immune system, activating a harmful inflammatory response that worsened skin infections in MRSA-infected mice.

The findings could have important clinical implications, given that the lives of many MRSA-infected patients are put at risk by initial inappropriate antibiotic treatment with beta-lactam antibiotics.

Currently, diagnostic procedures involve sending a sample to a lab where bacteria are allowed to grow for 2 days. However, newer tests that can detect staph DNA in a matter of hours are now becoming more widely available. This will help healthcare providers decide on the proper treatment regimen for a patient more quickly, potentially preventing deaths associated with inappropriate antibiotic treatment.

But the authors urge caution in extending the interpretation of this preclinical study to humans until more research is conducted.