(p)ppGpp and drug resistance.
In recent years, emerging and reemerging pathogens resistant to nearly all available antibiotics are on the rise. This limits the availability of effective antibiotics to treat infections, thus it is imperative to develop new drugs. The accumulation of alarmones guanosine tetraphosphate and guanosine pentaphosphate, collectively known as (p)ppGpp, is a global response of bacteria to environmental stress. (p)ppGpp has been documented to be involved in the resistance to beta-lactam and peptide antibiotics. Proposed mechanisms of action include occupation of drug targets, regulation of the expression of virulence determinants, and modification of protein activities. (p)ppGpp analogs might counteract these actions. Several such entities are being tested as new antibiotics. Further insights into the mechanisms of (p)ppGpp-mediated drug resistance might facilitate the discovery and development of novel antibiotics.
Wu
Jun
J
Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing, China.
Long
Quanxin
Q
Xie
Jianping
J
D004351:Drug Resistance; D004352:Drug Resistance, Microbial; D006158:Guanosine Pentaphosphate / Q000378:metabolism*; D047090:beta-Lactams / Q000737:chemistry / Q000378:metabolism
D047090:beta-Lactams; D006158:Guanosine Pentaphosphate