scholarly journals Staphylococcal Phage in Combination with Staphylococcus epidermidis as a Potential Treatment for Staphylococcus aureus-Associated Atopic Dermatitis and Suppressor of Phage-Resistant Mutants

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 7
Author(s):  
Yuzuki Shimamori ◽  
Shoichi Mitsunaka ◽  
Hirotaka Yamashita ◽  
Tohru Suzuki ◽  
Tomoe Kitao ◽  
...  

Atopic dermatitis is accompanied by the abnormal overgrowth of Staphylococcus aureus, a common cause of skin infections and an opportunistic pathogen. Although administration of antibiotics is effective against S. aureus, the resulting reduction in healthy microbiota and the emergence of drug-resistant bacteria are of concern. We propose that phage therapy can be an effective strategy to treat atopic dermatitis without perturbing the microbiota structure. In this study, we examined whether the S. aureus phage SaGU1 could be a tool to counteract the atopic exacerbation induced by S. aureus using an atopic mouse model. Administration of SaGU1 to the back skin of mice reduced both S. aureus counts and the disease exacerbation caused by S. aureus. Furthermore, the S. aureus-mediated exacerbation of atopic dermatitis with respect to IgE plasma concentration and histopathological findings was ameliorated by the application of SaGU1. We also found that Staphylococcus epidermidis, a typical epidermal symbiont in healthy skin, significantly attenuated the emergence of SaGU1-resistant S. aureus under co-culture with S. aureus and S. epidermidis in liquid culture infection experiments. Our results suggest that phage therapy using SaGU1 could be a promising clinical treatment for atopic dermatitis.

2021 ◽  
Vol 1 (5) ◽  
pp. 33-38
Author(s):  
K. S. Bordyugov ◽  
◽  
A. V. Pavlova ◽  
N. V. Pimenov ◽  
◽  
...  

The article provides data on the study of the qualitative composition of the microflora in purulent and fibrinous conjunctivitis in dogs. The proportion of microbial positive samples has been determined. The biological and biochemical properties of the isolated microorganisms have been studied. Studies have shown a high role of antibiotic-resistant bacteria Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumonia, Pseudomonas aeruginosa, E. coli, Enterobacter spp. in associations. The research results showed a high comparable effectiveness of phage therapy in the treatment of infectious-inflammatory pathologies of the organ of vision in dogs.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alan M O'Neill ◽  
Kate A Worthing ◽  
Nikhil Kulkarni ◽  
Fengwu Li ◽  
Teruaki Nakatsuji ◽  
...  

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP. A unique strain (S. felis C4) was isolated from feline skin that inhibited MRSP and multiple gram-positive pathogens. Whole genome sequencing and mass spectrometry revealed several secreted antimicrobials including a thiopeptide bacteriocin micrococcin P1 and phenol-soluble modulin beta (PSMβ) peptides that exhibited antimicrobial and anti-inflammatory activity. Fluorescence and electron microscopy revealed that S. felis antimicrobials inhibited translation and disrupted bacterial but not eukaryotic cell membranes. Competition experiments in mice showed that S. felis significantly reduced MRSP skin colonization and an antimicrobial extract from S. felis significantly reduced necrotic skin injury from MRSP infection. These findings indicate a feline commensal bacterium that could be utilized in bacteriotherapy against difficult-to-treat animal and human skin infections.


Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 149 ◽  
Author(s):  
Seitaro Nakagawa ◽  
Greg G. Hillebrand ◽  
Gabriel Nunez

Staphylococcus aureus is an opportunistic pathogen and a common cause of skin infection. S. aureus also plays a role in the pathogenesis of the chronic inflammatory skin disease, atopic dermatitis. S. aureus virulence involves activation of the quorum sensing agr operon. In this paper, we show that the diterpene carnosic acid, present in R. officinalis L. (rosemary) leaves, is a specific inhibitor of S. aureus agr expression as low as 5 μM. Carnosol and rosmarinic acid are two other phytochemicals present in rosemary leaves. Carnosol, but not rosmarinic acid, is also a potent agr expression inhibitor. Natural rosemary extracts containing carnosic acid and carnosol inhibit S. aureus agr expression, both in luciferase reporter strains and in wild type strains isolated from patients with atopic dermatitis. Specific inhibition of S. aureus virulence using topical formulations of rosemary extract may offer a practical approach to preventing and treating flares of atopic dermatitis.


Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 311 ◽  
Author(s):  
Supitchaya Traisaeng ◽  
Deron Raymond Herr ◽  
Hsin-Jou Kao ◽  
Tsung-Hsien Chuang ◽  
Chun-Ming Huang

The microbiome is a rich source of metabolites for the development of novel drugs. Butyric acid, for example, is a short-chain fatty acid fermentation metabolite of the skin probiotic bacterium Staphylococcus epidermidis (S. epidermidis). Glycerol fermentation of S. epidermidis resulted in the production of butyric acid and effectively hindered the growth of a Staphylococcus aureus (S. aureus) strain isolated from skin lesions of patients with atopic dermatitis (AD) in vitro and in vivo. This approach, however, is unlikely to be therapeutically useful since butyric acid is malodorous and requires a high concentration in the mM range for growth suppression of AD S. aureus. A derivative of butyric acid, BA–NH–NH–BA, was synthesized by conjugation of two butyric acids to both ends of an –NH–O–NH– linker. BA–NH–NH–BA significantly lowered the concentration of butyric acid required to inhibit the growth of AD S. aureus. Like butyric acid, BA–NH–NH–BA functioned as a histone deacetylase (HDAC) inhibitor by inducing the acetylation of Histone H3 lysine 9 (AcH3K9) in human keratinocytes. Furthermore, BA–NH–NH–BA ameliorated AD S. aureus-induced production of pro-inflammatory interleukin (IL)-6 and remarkably reduced the colonization of AD S. aureus in mouse skin. These results describe a novel derivative of a skin microbiome fermentation metabolite that exhibits anti-inflammatory and S. aureus bactericidal activity.


2020 ◽  
Vol 21 (1) ◽  
pp. 69-83 ◽  
Author(s):  
Marta Dec ◽  
Andrzej Wernicki ◽  
Renata Urban-Chmiel

AbstractBacteriophages are the most abundant form of life on earth and are present everywhere. The total number of bacteriophages has been estimated to be 1032 virions. The main division of bacteriophages is based on the type of nucleic acid (DNA or RNA) and on the structure of the capsid. Due to the significant increase in the number of multi-drug-resistant bacteria, bacteriophages could be a useful tool as an alternative to antibiotics in experimental therapies to prevent and to control bacterial infections in people and animals. The aim of this review was to discuss the history of phage therapy as a replacement for antibiotics, in response to EU regulations prohibiting the use of antibiotics in livestock, and to present current examples and results of experimental phage treatments in comparison to antibiotics. The use of bacteriophages to control human infections has had a high success rate, especially in mixed infections caused mainly by Staphylococcus, Pseudomonas, Enterobacter, and Enterococcus. Bacteriophages have also proven to be an effective tool in experimental treatments for combating diseases in livestock.


2019 ◽  
Vol 20 (16) ◽  
pp. 4041 ◽  
Author(s):  
Deborah Palazzotti ◽  
Maicol Bissaro ◽  
Giovanni Bolcato ◽  
Andrea Astolfi ◽  
Tommaso Felicetti ◽  
...  

The use and misuse of antibiotics has resulted in critical conditions for drug-resistant bacteria emergency, accelerating the development of antimicrobial resistance (AMR). In this context, the co-administration of an antibiotic with a compound able to restore sufficient antibacterial activity may be a successful strategy. In particular, the identification of efflux pump inhibitors (EPIs) holds promise for new antibiotic resistance breakers (ARBs). Indeed, bacterial efflux pumps have a key role in AMR development; for instance, NorA efflux pump contributes to Staphylococcus aureus (S. aureus) resistance against fluoroquinolone antibiotics (e.g., ciprofloxacin) by promoting their active extrusion from the cells. Even though NorA efflux pump is known to be a potential target for EPIs development, the absence of structural information about this protein and the little knowledge available on its mechanism of action have strongly hampered rational drug discovery efforts in this area. In the present work, we investigated at the molecular level the substrate recognition pathway of NorA through a Supervised Molecular Dynamics (SuMD) approach, using a NorA homology model. Specific amino acids were identified as playing a key role in the efflux pump-mediated extrusion of its substrate, paving the way for a deeper understanding of both the mechanisms of action and the inhibition of such efflux pumps.


Dermatology ◽  
1997 ◽  
Vol 195 (1) ◽  
pp. 6-9 ◽  
Author(s):  
H. Kanzaki ◽  
M. Ueda ◽  
Y. Morishita ◽  
H. Akiyama ◽  
J. Arata ◽  
...  

1997 ◽  
Vol 25 (6) ◽  
pp. 318-324 ◽  
Author(s):  
S Higaki ◽  
S Mommatsu ◽  
M Morohashi ◽  
T Yamagishi ◽  
Y Hasegawa

We examined the in vitro sensitivities of three bacteria: Propionibacterium acnes, and Staphylococcus epidermidis, commonly detected in acne lesions, and Staphylococcus aureus, a common cause of skin infections, to 10 Kampo formulations (Chinese herbal medicines; combinations of powdered extracts of crude drugs). Both Staphylococcus species showed similar sensitivities to all 10 formulations, with minimum inhibitory concentrations (MICs) ranging from 25 to 400 mg/ml. P. acnes, however, was particularly sensitive to one formulation, keigai-rengyo-to (MIC, 0.78 – 25 mg/ml), prompting speculation that it might contain components with strong antibacterial activity to P. acnes. P. acnes showed similar sensitivities to all the other formulations (MIC 6.25 – 200 mg/ml). The ranges of MICs and the MIC50s (concentrations that inhibit 50% of isolates) were very similar to those previously recorded in 1990 for the two Staphylococcus species.


2019 ◽  
Vol 35 (10) ◽  
pp. 806-809 ◽  
Author(s):  
Bertrand Jordan

Bacteriophages were advocated as therapeutic agents more than a century ago, but the advent of antibiotics relegated them to a very minor role. Today, multi-drug resistant bacteria are a serious health problem, and phage therapy enjoys renewed interest. Recent publications show that it can be effective, but also highlight the serious logistic problems involved in using this approach.


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