Shenderovich, J. | Search bioRxiv

bioRxiv2025

Gastrointestinal colonization as a source of Staphylococcus aureus in atopic dermatitis

Atopic dermatitis (AD) is a prevalent inflammatory skin disease with complex pathogenesis. Both skin and gut microbiota influence AD, with Staphylococcus aureus, in particular, exacerbating the disease. However, the relationship between S. aureus colonization in the gut and skin, and whether it affects AD, remains unclear. Using a combination of culture-based methods, microbiome analysis, and genome sequencing of S. aureus from multiple body sites of children with and without AD, we found that the gut represents a major reservoir of genetically diverse S. aureus that is transmitted to the skin, including mutants associated with worse disease. We validated this association between S. aureus gastrointestinal colonization and AD in an independent human cohort and demonstrated its direct effect on disease in an infantile AD mouse model, wherein S. aureus gastrointestinal colonization worsened skin inflammation. Overall, this study identifies a previously unrecognized S. aureus reservoir, with implications for microbiota-targeting therapies in AD.

microbiology↗

bioRxiv2023

Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr increased both respiration and fermentation but decreased ATP levels and growth, suggesting that {Delta}agr cells assume a hyperactive metabolic state in response to reduced metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of {Delta}agr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected {Delta}agr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived "memory" of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Nox2-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

microbiology↗