Metabolic niche adaptation of community- and hospital-associated methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) originally emerged in nosocomial settings and has subsequently spread into the community. In turn, community-associated (CA) MRSA lineages are nowadays introduced from the community into hospitals where they can cause hospital-associated (HA) infections. This raises the question of how the CA-MRSA lineages adapt to the hospital environment. Previous studies implicated particular virulence factors in the CA-behaviour of MRSA. However, we hypothesized that physiological changes may also impact staphylococcal epidemiology. With the aim to identify potential metabolic adaptations, we comparatively profiled the cytosolic proteomes of CA- and HA-isolates from the USA300 lineage that was originally identified as CA-MRSA. Interestingly, enzymes for gluconeogenesis, the tricarboxylic acid cycle and biosynthesis of amino acids are up-regulated in the investigated CA-MRSA isolates, while enzymes for glycolysis and the pentose phosphate pathway are up-regulated in the HA-MRSA isolates. Of note, these data apparently match with the clinical presentation of each group. These observations spark interest in central carbon metabolism as a key driver for adaptations that streamline MRSA for propagation in the community or the hospital.

A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis.

RATIONALE: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation, and atherosclerosis has not been explored previously. OBJECTIVE: Here, we investigated whether a proinflammatory microbiota from Caspase1-/- ( Casp1-/-) mice accelerates atherogenesis in Ldlr-/- mice. METHOD AND RESULTS: We treated female Ldlr-/- mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1-/- mice based on a cohousing approach. Autologous transplantation of fecal microbiota of Ldlr-/- mice served as control. Mice were cohoused for 8 or 13 weeks and fed chow or high-fat cholesterol-rich diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health, and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA (ribosomal DNA) sequences confirmed the introduction of the Casp1-/- and Ldlr-/- microbiota into Ldlr-/- mice (referred to as Ldlr-/-( Casp1-/-) or Ldlr-/-( Ldlr-/-) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week high-fat cholesterol-fed Ldlr-/-( Casp1-/-) mice compared with Ldlr-/-( Ldlr-/-) mice. We found increased numbers of circulating monocytes and neutrophils and elevated proinflammatory cytokine levels in plasma in high-fat cholesterol-fed Ldlr-/-( Casp1-/-) compared with Ldlr-/-( Ldlr-/-) mice. Neutrophil accumulation in the aortic root of Ldlr-/-( Casp1-/-) mice was enhanced compared with Ldlr-/-( Ldlr-/-) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid-producing taxonomies Akkermansia, Christensenellaceae, Clostridium, and Odoribacter in Ldlr-/-( Casp1-/-) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory short-chain fatty acids propionate, acetate and butyrate in the cecum were significantly reduced in 13-week high-fat cholesterol-fed Ldlr-/-( Casp1-/-) compared with Ldlr-/-( Ldlr-/-) mice. CONCLUSIONS: Introduction of the proinflammatory Casp1-/- microbiota into Ldlr-/- mice enhances systemic inflammation and accelerates atherogenesis.