Methicillin-resistant Staphylococcus pseudintermedius synthesizes deoxyadenosine to cause persistent infection

Area of Science:

• Microbiology
• Infectious Diseases
• Genomics

Background:

• Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is a zoonotic pathogen originating from canines, causing severe diseases like bacteremia and endocarditis.
• Despite genomic insights, the specific virulence factors driving MRSP pathogenesis in humans and canines remain largely unknown.

Purpose of the Study:

• To identify key virulence factors contributing to MRSP pathogenesis.
• To elucidate the mechanism by which MRSP evades host immune responses.

Main Methods:

• Generation of genetically engineered MRSP variants.
• Utilized a mouse abscess model to study MRSP infection.
• Bioinformatics analyses to assess the prevalence of identified genes.

Main Results:

• Identified the secreted nuclease NucB and adenosine synthase A (AdsA) as crucial for MRSP pathogenesis.
• Demonstrated that NucB and AdsA act synergistically to degrade host DNA, leading to cytotoxic deoxyadenosine production.
• Showed that MRSP selectively kills macrophages, impairing host immune responses during abscess formation.
• Bioinformatics confirmed NucB and AdsA are widespread in the global MRSP population.

Conclusions:

• MRSP utilizes the NucB/AdsA pathway, similar to Staphylococcus aureus, to degrade DNA and antagonize host immunity.
• This mechanism is essential for MRSP persistence during invasive infections.
• The identified NucB/AdsA pathway presents a potential target for novel therapeutic strategies against MRSP infections.