Medicine: The stringent response can influence antibiotic resistance

Contributed by paustian on Jan 03, 2017 - 01:37 PM

Cancer is a horrible disease, killing over half a million people in the United States every year and is the leading, or second cause of death in most states. It is especially horrific when it affects children. Great strides have been made in cancer therapy in children, increasing rates of 5 year survival for some cancers above 80%. Some treatments, especially when treating leukemia, require the killing of all white blood cells, which can leave the patient open to infection. Work by Honsa et al. describes the persistent infection of a 6-week-old infant with vancomycin-resistant enterococcus (VRE). Even with appropriate treatment against the infection the VRE was able to survive. The infection was eventually cleared when the patients immune system came back online 26 days later.

Curious how VRE survived treatment that was demonstrated to be able to kill it, the scientists sequenced 22 isolates obtained from the patient over the course of the infection. A single mutation in the relA gene was discovered that induced the stringent response. This response is normally turned on when the microbe is experiencing stress, such as starvation. The mutant was still susceptible to linezolid and daptomycin when in the test tube, and when growing individually, but and it had increased resistance to these antibiotics when growing in a biofilm. The addition of a compound that disrupts biofilm formation, caused the microbe to again be susceptible to the antibiotics.

The work demonstrates a new method of approach to treat persistent infections and also indicates the stress response in resisting antibiotics. It also shows the importance of our immune systems in fighting infections, even when treated with antibiotics.