RelA Mutant Enterococcus faecium with Multiantibiotic Tolerance Arising in an Immunocompromised Host.
Erin S HonsaVaughn S CooperMohammed N MhaissenMatthew FrankJessica ShakerAmy IversonJeffrey RubnitzRandall T HaydenRichard E LeeCharles O RockElaine I TuomanenJoshua WolfJason W RoschPublished in: mBio (2017)
The increasing prevalence of antibiotic-resistant bacterial pathogens is a major challenge currently facing the medical community. Such pathogens are of particular importance in immunocompromised patients as these individuals may favor emergence of novel resistance determinants due to lack of innate immune defenses and intensive antibiotic exposure. During the course of chemotherapy, a patient developed prolonged bacteremia with vancomycin-resistant Enterococcus faecium that failed to clear despite multiple front-line antibiotics. The consecutive bloodstream isolates were sequenced, and a single missense mutation identified in the relA gene, the mediator of the stringent response. Strains harboring the mutation had elevated baseline levels of the alarmone and displayed heightened resistance to the bactericidal activity of multiple antibiotics, particularly in a biofilm. Using a new class of compounds that modulate ClpP activity, the biofilms were successfully eradicated. These data represent the first clinical emergence of mutations in the stringent response in vancomycin-resistant entereococci.
Keyphrases
- gram negative
- innate immune
- biofilm formation
- end stage renal disease
- healthcare
- methicillin resistant staphylococcus aureus
- candida albicans
- newly diagnosed
- staphylococcus aureus
- chronic kidney disease
- pseudomonas aeruginosa
- ejection fraction
- multidrug resistant
- mental health
- escherichia coli
- risk factors
- genome wide
- squamous cell carcinoma
- big data
- respiratory failure
- copy number
- patient reported outcomes
- dna methylation
- gene expression
- transcription factor
- extracorporeal membrane oxygenation