Maghnus O'Seaghdha

• PhD
• Professor (Assistant) at Suffolk University

The nervous system, the immune system, and microbial pathogens interact closely at barrier tissues. Here, we find that a bacterial pathogen, Streptococcus pyogenes, hijacks pain and neuronal regulation of the immune response to promote bacterial survival. Necrotizing fasciitis is a life-threatening soft tissue infection in which "pain is out of pro...

The globally dominant, invasive M1T1 strain of group A Streptococcus (GAS) harbors polymorphisms in the promoter region of an operon that contains the genes encoding streptolysin O (SLO) and NAD⁺-glycohydrolase (NADase), resulting in high-level expression of these toxins. While both toxins have been shown experimentally to contribute to pathogenesi...

Group A Streptococcus (GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD⁺-g...

A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS) has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase). When GAS binds to epithelial cells in vitro, NADase is tran...

Schematic diagrams of expression constructs for recombinant proteins prepared in this study. (PDF)

Evidence that enzymatically inactive variants of NADase retain their native conformations after purification. (A) Ability of enzymatically inactive variants of LFn-NADase to compete for binding of NADase to IFS. Plots demonstrate dose-dependent inhibition of NADase activity. Reactions contained 35 nM NADase, 70 nM IFS, and the indicated concentrati...

Dependence on PA of LFn-NADase translocation into OKP7 keratinocytes. Data represent inhibition of protein synthesis by PA-mediated translocation of LFn-NADase in OKP7 cells. Protein synthesis was assayed by incorporation of tritiated leucine and is plotted as the fraction of activity in OKP7 cells in the absence of recombinant protein. Inhibition...

Intracellular delivery of NADase varies with multiplicity of infection. NADase activity was measured in the cytosolic fraction of OKP7 cell lysates after 2 hours exposure of OKP7 cells to GAS strain 188 at the indicated multiplicity of infection. Values represent mean±SEM from three independent experiments. (PDF)

Increase in NADase melting temperature associated with binding of IFS. Plots represent melting curves of NADase, IFS, and NADase-IFS complex as determined by differential scanning fluorimetry. The peak of the curve of the first derivative of the measured fluorescence intensity, plotted as a function of temperature, represents the melting temperatur...

Induction of autophagy in OKP7 cells by GAS or purified recombinant SLO. A. GAS strain JRS4 and JRS4SLO- enter autophagosome-like compartments in OKP7 oropharyngeal keratinocytes. B. In HeLa cells, GAS localization to autophagosomes is SLO-dependent. HeLa cells stably expressing EGFP-LC3 were exposed to GAS strains 188 or 188SLO- (SLO-), and the as...

Intracellular survival of GAS in HeLa cells and cytotoxic effects of GAS on HeLa and OKP7 cells. A. Intracellular survival in HeLa was determined as described above for strains 188 and 188SLO- (SLO-). Data represent mean±SD of three independent experiments. *, P<0.001. B. LDH release was measured at 2 h post-infection to determine cytotoxicity to H...

GAS strains used in this study. (PDF)

siRNA knockdown of becn1 (Beclin 1). Lysates from OKP7 cells treated with non-targeting siRNA (non-target) or an siRNA pool directed against Beclin 1 (becn1) were analyzed by Western blot for Beclin 1 production. GAPDH was used as a loading control. (PDF)

Oligonucleotide primers used in this study. (PDF)

A GAS strain engineered to secrete the endogenous NADase inhibitor IFS exhibits impaired intracellular survival. A. Intracellular survival of strain 188 expressing a secreted FLAG-tagged GAS NADase inhibitor IFS from an expression vector (188(pSEC-IFS)) or strain 188 or 188NADase- carrying empty vector (188(pDL278) or NADase-(pDL278), respectively)...

Group A Streptococcus (Streptococcus pyogenes or GAS) causes pharyngitis, severe invasive infections, and the post-infectious syndromes of glomerulonephritis and rheumatic fever. GAS can be internalized and killed by epithelial cells in vitro, a process that may contribute to local innate defense against pharyngeal infection. Secretion of the pore-...

Osteomyelitis is a debilitating infectious disease of the bone. It is predominantly caused by S. aureus and is associated with significant morbidity and mortality. It is characterised by weakened bones associated with progressive bone loss. Currently the mechanism through which either bone loss or bone destruction occurs in osteomyelitis patients i...

The activation of type I IFN signaling is a major component of host defense against viral infection, but it is not typically associated with immune responses to extracellular bacterial pathogens. Using mouse and human airway epithelial cells, we have demonstrated that Staphylococcus aureus activates type I IFN signaling, which contributes to its vi...

Staphylococcal immunoglobulin-binding protein, Sbi, is a 436-residue protein produced by many strains of Staphylococcus aureus. It was previously characterized as being cell surface-associated and having binding capacity for human IgG and β2-glycoprotein I. Here we show using small angle x-ray scattering that the proposed extracellular region of Sb...

Among the many adhesins and toxins expressed by Staphylococcus aureus, protein A is an exceptionally complex virulence factor, known to interact with multiple eukaryotic targets, particularly those with immunological functions. Protein A acts as a ligand that can mimic TNF-alpha to activate TNFR1 and subsequent proinflammatory signaling. It also st...

Protein A (Spa) is a surface-associated protein of Staphylococcus aureus best known for its ability to bind to the Fc region of IgG. Spa also binds strongly to the Fab region of the immunoglobulins bearing V(H)3 heavy chains and to von Willebrand factor (vWF). Previous studies have suggested that the protein A-vWF interaction is important in S. aur...

Staphylococcus aureus continues to be a major cause of infection in normal as well as immunocompromised hosts, and the increasing prevalence of highly virulent community-acquired methicillin-resistant strains is a public health concern. A highly expressed surface component of S. aureus, protein A (SpA), contributes to its success as a pathogen by b...