Dataset Information

Probiotic Exopolysaccharide Protects against Systemic Staphylococcus aureus Infection, Inducing Dual-Functioning Macrophages That Restrict Bacterial Growth and Limit Inflammation.

ABSTRACT: Staphylococcus aureus causes severe systemic infection with high mortality rates. We previously identified exopolysaccharide (EPS) from a probiotic, Bacillus subtilis, that induces anti-inflammatory macrophages with an M2 phenotype and protects mice from Citrobacter rodentium-induced colitis. We tested if EPS could protect from systemic infection induced by S. aureus and found that EPS-treated mice had enhanced survival as well as reduced weight loss, systemic inflammation, and bacterial burden. While macrophages from EPS-treated mice display an M2 phenotype, they also restrict growth of internalized S. aureus through reactive oxygen species (ROS), reminiscent of proinflammatory phagocytes. These EPS-induced macrophages also limit T cell activation by S. aureus superantigens, and EPS abrogates systemic induction of gamma interferon after infection. We conclude that B. subtilis EPS is an immunomodulatory agent that induces hybrid macrophages that bolster antibacterial immunity and simultaneously limit inflammation, reducing disease burden and promoting host survival.

SUBMITTER: Paik W

PROVIDER: S-EPMC6300633 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Probiotic Exopolysaccharide Protects against Systemic Staphylococcus aureus Infection, Inducing Dual-Functioning Macrophages That Restrict Bacterial Growth and Limit Inflammation.

Paik Wonbeom W Alonzo Francis F Knight Katherine L KL

Infection and immunity 20181219 1

Staphylococcus aureus causes severe systemic infection with high mortality rates. We previously identified exopolysaccharide (EPS) from a probiotic, Bacillus subtilis, that induces anti-inflammatory macrophages with an M2 phenotype and protects mice from Citrobacter rodentium-induced colitis. We tested if EPS could protect from systemic infection induced by S. aureus and found that EPS-treated mice had enhanced survival as well as reduced weight loss, systemic inflamm ...[more]

PMID: 30396894

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Project description:Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureusin vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner.IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

Dataset Information

Probiotic Exopolysaccharide Protects against Systemic Staphylococcus aureus Infection, Inducing Dual-Functioning Macrophages That Restrict Bacterial Growth and Limit Inflammation.

Publications

Probiotic Exopolysaccharide Protects against Systemic <i>Staphylococcus aureus</i> Infection, Inducing Dual-Functioning Macrophages That Restrict Bacterial Growth and Limit Inflammation.

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