Biology subjects

Karagounis, T. K.

Publications and source records attributed to Karagounis, T. K..

3 recordsLinked to original sources

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↗

bioRxiv2024

Prophage-encoded methyltransferase drives adaptation of community-acquired methicillin-resistant Staphylococcus aureus

We recently described the evolution of a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 variant responsible for an outbreak of skin and soft tissue infections. Acquisition of a mosaic version of the {Phi}11 prophage (m{Phi}11) that increases skin abscess size was an early step in CA-MRSA adaptation that primed the successful spread of the clone. The present report shows how prophage m{Phi}11 exerts its effect on virulence for skin infection without encoding a known toxin or fitness genes. Abscess size and skin inflammation were associated with DNA methylase activity of an m{Phi}11-encoded adenine methyltransferase (designated pamA). pamA increased expression of fibronectin-binding protein A (fnbA; FnBPA), and inactivation of fnbA eliminated the effect of pamA on abscess virulence without affecting strains lacking pamA. Thus, fnbA is a pamA-specific virulence factor. Mechanistically, pamA was shown to promote biofilm formation in vivo in skin abscesses, a phenotype linked to FnBPAs role in biofilm formation. Collectively, these data reveal a novel mechanism--epigenetic regulation of staphylococcal gene expression--by which phage can regulate virulence to drive adaptive leaps by S. aureus. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/589803v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@b97d6forg.highwire.dtl.DTLVardef@1da30f1org.highwire.dtl.DTLVardef@1c34311org.highwire.dtl.DTLVardef@6834df_HPS_FORMAT_FIGEXP M_FIG C_FIG

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↗