DNA methylation and MRSA persistence

Researchers report that host DNA methylation signatures differentiate persistent and resolving methicillin-resistant Staphylococcus aureus (MRSA) infections. A substantial share of MRSA infections fail to resolve despite treatment with antibiotics to which the bacteria are susceptible in vitro. Such antibiotic-persistent MRSA bacteremia (APMB) is life-threatening and often prompts the use of additional antibiotics that can compound resistance. The mechanisms responsible for APMB are not understood but are thought to involve host-pathogen interactions. Elaine Reed and colleagues used genome-wide and targeted bisulfite sequencing methods along with bioinformatic analyses to explore the relationship between host DNA methylation patterns and APMB in 142 patients with S. aureus bacteremia. The authors identified 276 host genomic sites where methylation differed significantly between antibiotic-persistent and antibiotic-resolving cases. These sites tended to localize to binding sites for specific transcription factors, particularly in enhancer regions regulating proteins involved in immune cell signaling. Methylation differences were more pronounced in certain immune cell types, such as neutrophils, than in others. The results suggest that DNA methylation epigenotypes in specific immune cells could be used to assess the likelihood of APMB at the first signs of infection and to guide preemptive, targeted interventions to prevent persistence and improve outcomes, according to the authors.

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Article #20-00663: “Human DNA Methylation Signatures Differentiate Persistent from Resolving MRSA Bacteremia,” by Yu-Ling Chang et al.

MEDIA CONTACT: Elaine F. Reed, David Geffen School of Medicine at UCLA, Los Angeles, CA; tel: 310-794-4943, 310-463-5337; email: <

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>; Michael R. Yeaman, David Geffen School of Medicine at UCLA, Los Angeles, CA; tel: 310-222-6428, 310-729-7762; email: <

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