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PEG-8 Laurate Fermentation of Staphylococcus epidermidis Reduces the Required Dose of Clindamycin Against Cutibacterium acnes.

ABSTRACT: The probiotic activity of skin Staphylococcus epidermidis (S. epidermidis) bacteria can elicit diverse biological functions via the fermentation of various carbon sources. Here, we found that polyethylene glycol (PEG)-8 Laurate, a carbon-rich molecule, can selectively induce the fermentation of S. epidermidis, not Cutibacterium acnes (C. acnes), a bacterium associated with acne vulgaris. The PEG-8 Laurate fermentation of S. epidermidis remarkably diminished the growth of C. acnes and the C. acnes-induced production of pro-inflammatory macrophage-inflammatory protein 2 (MIP-2) cytokines in mice. Fermentation media enhanced the anti-C. acnes activity of a low dose (0.1%) clindamycin, a prescription antibiotic commonly used to treat acne vulgaris, in terms of the suppression of C. acnes colonization and MIP-2 production. Furthermore, PEG-8 Laurate fermentation of S. epidermidis boosted the activity of 0.1% clindamycin to reduce the sizes of C. acnes colonies. Our results demonstrated, for the first time, that the PEG-8 Laurate fermentation of S. epidermidis displayed the adjuvant effect on promoting the efficacy of low-dose clindamycin against C. acnes. Targeting C. acnes by lowering the required doses of antibiotics may avoid the risk of creating drug-resistant C. acnes and maintain the bacterial homeostasis in the skin microbiome, leading to a novel modality for the antibiotic treatment of acne vulgaris.

SUBMITTER: Marito S

PROVIDER: S-EPMC7404057 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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PEG-8 Laurate Fermentation of Staphylococcus epidermidis Reduces the Required Dose of Clindamycin Against Cutibacterium acnes.

Marito Shinta S Keshari Sunita S Huang Chun-Ming CM

International journal of molecular sciences 20200719 14

The probiotic activity of skin Staphylococcus epidermidis (S. epidermidis) bacteria can elicit diverse biological functions via the fermentation of various carbon sources. Here, we found that polyethylene glycol (PEG)-8 Laurate, a carbon-rich molecule, can selectively induce the fermentation of S. epidermidis, not Cutibacterium acnes (C. acnes), a bacterium associated with acne vulgaris. The PEG-8 Laurate fermentation of S. epidermidis remarkably diminis ...[more]

PMID: 32707723

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Project description:Cutibacterium acnes is a human skin-resident bacterium. Although C. acnes maintains skin health by inhibiting invasion from pathogens like Staphylococcus aureus, it also contributes to several diseases, including acne. Studies suggest that differences in genetic background may explain the diverse phenotypes of C. acnes strains. In this study, we investigated the effects of C. acnes strains on the Caenorhabditis elegans life span and observed that some strains shortened the life span, whereas other strains, such as strain HL110PA4, did not alter it. Next, we assessed the effects of C. acnes HL110PA4 on host resistance against S. aureus. The survival time of C. acnes HL110PA4-fed wild-type animals was significantly longer than that of Escherichia coli OP50 control bacterium-fed worms upon infection with S. aureus. Although the survival times of worms harboring mutations at the daf-16/FoxO and skn-1/Nrf2 loci were similar to those of wild-type worms after S. aureus infection, administration of C. acnes failed to improve survival times of tir-1/SARM1, nsy-1/mitogen-activated protein kinase kinase kinase (MAPKKK), sek-1/mitogen-activated protein kinase kinase (MAPKK), and pmk-1/p38 mitogen-activated protein kinase (MAPK) mutants. These results suggest that the TIR-1 and p38 MAPK pathways are involved in conferring host resistance against S. aureus in a C. acnes-mediated manner. IMPORTANCE Cutibacterium acnes is one of the most common bacterial species residing on the human skin. Although the pathogenic properties of C. acnes, such as its association with acne vulgaris, have been widely described, its beneficial aspects have not been well characterized. Our study classifies C. acnes strains based on its pathogenic potential toward the model host C. elegans and reveals that the life span of C. elegans worms fed on C. acnes was consistent with the clinical association of C. acnes ribotypes with acne or nonacne. Furthermore, nonpathogenic C. acnes confers host resistance against the opportunistic pathogen Staphylococcus aureus. Our study provides insights into the impact of C. acnes on the host immune system and its potential roles in the ecosystem of skin microbiota.

Project description:BACKGROUND AND OBJECTIVES:The emergence of resistant strains of Cutibacterium acnes can limit the efficacy of currently approved antibiotics for acne. VB-1953 is a next-generation antibiotic that exerts a bactericidal effect on resistant C. acnes. In this study, we investigated the safety, tolerability, and efficacy of VB-1953 topical gel in patients with moderate to severe acne having clindamycin-resistant C. acnes. METHODS:An investigator-initiated, open label, single-arm clinical study was conducted in patients with moderate to severe facial acne vulgaris showing poor or no response to previous clindamycin treatment. Nineteen subjects were enrolled in the study based on laboratory screening for the presence of clindamycin-resistant C. acnes in acne swab samples collected from patients. VB-1953 2% gel was applied on the entire face twice daily over 12 weeks. The primary efficacy endpoints were absolute changes in inflammatory and noninflammatory lesion counts from baseline at week 12, while the secondary efficacy endpoint was the proportion of subjects achieving Investigator Global Assessment success (score of 0 or 1) or a grade 2 or higher improvement from baseline at week 12. The presence and severity of local skin reactions (erythema, edema, scaling/dryness, burning/stinging, pruritus) were evaluated for safety. Additionally, the detection and quantification of drug-resistant C. acnes strains were performed in the laboratory using acne swab samples collected from patients. RESULTS:The occurrence of treatment-emergent adverse events or changes in vital signs, physical examinations, and urinalysis for any of the patients during the course of the entire study were clinically insignificant. Topical application of 2% VB-1953 topical gel resulted in a significant reduction of mean absolute inflammatory and noninflammatory lesion counts by 53.1% and 52.2%, respectively (p?<?0.0001 for both), with an Investigator Global Assessment success of 26.3% at week 12 compared with baseline. Resistant bacteria were reduced by (94.3?±?1%; p?<?0.05) within 12 weeks of treatment with VB-1953. CONCLUSION:These results indicate that VB-1953 topical gel can be a safe and effective therapy for moderate to severe acne with underlying resistant C. acnes in subjects who had not responded to previous antibiotic treatments.

Project description:Propionibacterium acnes and Staphylococcus epidermidis live in close proximity on human skin, and both bacterial species can be isolated from normal and acne vulgaris-affected skin sites. The antagonistic interactions between the two species are poorly understood, as well as the potential significance of bacterial interferences for the skin microbiota. Here, we performed simultaneous antagonism assays to detect inhibitory activities between multiple isolates of the two species. Selected strains were sequenced to identify the genomic basis of their antimicrobial phenotypes.First, we screened 77 P. acnes strains isolated from healthy and acne-affected skin, and representing all known phylogenetic clades (I, II, and III), for their antimicrobial activities against 12 S. epidermidis isolates. One particular phylogroup (I-2) exhibited a higher antimicrobial activity than other P. acnes phylogroups. All genomes of type I-2 strains carry an island encoding the biosynthesis of a thiopeptide with possible antimicrobial activity against S. epidermidis. Second, 20 S. epidermidis isolates were examined for inhibitory activity against 25 P. acnes strains. The majority of S. epidermidis strains were able to inhibit P. acnes. Genomes of S. epidermidis strains with strong, medium and no inhibitory activities against P. acnes were sequenced. Genome comparison underlined the diversity of S. epidermidis and detected multiple clade- or strain-specific mobile genetic elements encoding a variety of functions important in antibiotic and stress resistance, biofilm formation and interbacterial competition, including bacteriocins such as epidermin. One isolate with an extraordinary antimicrobial activity against P. acnes harbors a functional ESAT-6 secretion system that might be involved in the antimicrobial activity against P. acnes via the secretion of polymorphic toxins.Taken together, our study suggests that interspecies interactions could potentially jeopardize balances in the skin microbiota. In particular, S. epidermidis strains possess an arsenal of different mechanisms to inhibit P. acnes. However, if such interactions are relevant in skin disorders such as acne vulgaris remains questionable, since no difference in the antimicrobial activity against, or the sensitivity towards S. epidermidis could be detected between health- and acne-associated strains of P. acnes.

Dataset Information

PEG-8 Laurate Fermentation of Staphylococcus epidermidis Reduces the Required Dose of Clindamycin Against Cutibacterium acnes.

Publications

PEG-8 Laurate Fermentation of <i>Staphylococcus epidermidis</i> Reduces the Required Dose of Clindamycin Against <i>Cutibacterium acnes</i>.

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