Differing Virulence of Healthy Skin Commensals in Mouse Models of Infection

Abstract

Introduction: As therapies for atopic dermatitis (AD) based on live biotherapeutic products (LBP) are developed, the potential displacement of biotherapeutic strains, and species to mucosal sites where they are not naturally found is of investigative interest. However, formal assessment of the toxicity potential of healthy skin commensal organisms has not been reported in the literature. Our previous research indicates that topical application of live Roseomonas mucosa to treat AD was associated with clinical benefit on the skin, but the effects of exposure via inhalation, eye inoculation, and ingestion were unknown.Methods: Herein we report our findings from mice inoculated with commensal strains of R. mucosa, coagulase negative Staphylococci (CNS), and Pseudomonas aeruginosa. Bacterial isolates were collected under clinical trial NCT03018275, however these results do not represent an interventional clinical trial.Results: Our tested R. mucosa isolates did not display significant infection or inflammation. However, neutropenic mice inoculated with CNS had infection without major inflammation in pulmonary models. In contrast, systemic infection generated hepatic and splenic pathology for P. aeruginosa and CNS, which was worsened by the presence of neutropenia.Discussion: Our results suggest that LBP derived from bacteria without significant infectivity histories, such as R. mucosa, may represent safer options than known pathobionts like P. aeruginosa and Staphylococcus spp. Overall, these results suggest that topically applied LBP from select skin commensals are likely to present safe therapeutic options and reinforce our prior clinical findings.

Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair

“…3, G and H) was similar to the culture yields from patients with AD after treatment (Fig. 3F) and healthy controls (25).…”

“…Coisolation of R. mucosa with quintessential catheter pathogens like S. aureus in these studies additionally suggested a low virulence potential for R. mucosa given the recognized pathogenic potential of S. aureus. Safety claims for R. mucosa are further supported by the failure of RmHV to generate notable pathology or infection after direct inoculation into the eyes, lungs, stomach, and veins of mice, in contrast to the morbidity and mortality seen with other skin commensals from healthy volunteers (3,25). Thus, R. mucosa has yet to fulfill Koch's postulates for defining agents that cause infectious diseases.…”

Microbial manipulation in atopic dermatitis

“…Yet even in the absence of resistance, antibiotics have not been shown to improve the symptoms of AD, and treatment guidelines explicitly recommend against the use of topical or oral antibiotics unless clinical signs of frank cellulitis are present 3,14 . Furthermore, attempting to curtail S. aureus through topical use of CoNS‐containing probiotics 3 presents an experimental risk of infecting patients with the treatment strain 15 …”

“… 3 , 14 Furthermore, attempting to curtail S. aureus through topical use of CoNS‐containing probiotics 3 presents an experimental risk of infecting patients with the treatment strain. 15 …”

“…3,14 Furthermore, attempting to curtail S. aureus through topical use of CoNS-containing probiotics 3 presents an experimental risk of infecting patients with the treatment strain. 15 However, Weiss et al, 16 aim to succeed where prior anti-S. aureus strategies have failed through several unique innovations. In their study, the authors demonstrated the potent anti-staphylococcal activity of niclosamide, a traditional antihelminthic drug.…”