Translocating bacteria in SIV infection are not stochastic and preferentially express cytosine methyltransferases

Area of Science:

• Microbiology
• Immunology
• Virology

Background:

• Microbial translocation contributes to chronic inflammation and poor outcomes in people living with HIV (PLWH).
• Current therapeutics for microbial translocation show limited efficacy due to incompletely characterized contributing species and mechanisms.
• Chronic SIV infection in rhesus macaques serves as a model for HIV to study microbial translocation.

Purpose of the Study:

• To identify bacterial species and mechanisms driving microbial translocation in lentiviral infection.
• To investigate the potential of targeting bacterial cytosine methyltransferases as a therapeutic strategy.
• To evaluate the efficacy of decitabine in reducing translocating bacteria in vitro and in vivo.

Main Methods:

• Culturing of translocating bacteria from SIV-infected rhesus macaques.
• Proteomic profiling to identify common bacterial features.
• In vitro growth inhibition assays using decitabine.
• In vivo oral administration of decitabine to SIV-infected rhesus macaques and analysis of gut microbiome.

Main Results:

• Proteomic analysis identified cytosine-specific methyltransferases as a common feature in translocating bacteria.
• Decitabine significantly inhibited the growth of several translocating bacterial species in vitro.
• Oral decitabine treatment resulted in transient reductions of translocator taxa in the gut microbiome of treated macaques.

Conclusions:

• Cytosine methyltransferases are potential drivers of bacterial translocation in lentiviral infections.
• Decitabine demonstrates potential as a therapeutic agent to mitigate microbial translocation.
• Further research into decitabine and related inhibitors may offer novel interventions to improve outcomes for PLWH.