Publications

PubMed (NCBI) References 

Featured below: Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis 

- Science Translational Medicine article abstract 


S. aureus aggravates skin conditions such as atopic dermatitis. Photo courtesy of NIAID.

Teruaki Nakatsuji, Tiffany H. Chen, Saisindhu Narala, Kimberly A. Chun, Aimee M. Two, Tong Yun, Faiza Shafiq, Paul F. Kotol, Amina Bouslimani, Alexey V. Melnik, Haythem Latif, Ji-Nu Kim, Alexandre Lockhart, Keli Artis, Gloria David, Patricia Taylor, Joanne Streib, Pieter C. Dorrestein, Alex Grier, Steven R. Gill, Karsten Zengler, Tissa R. Hata, Donald Y. M. Leung and Richard L. Gallo  

The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus. The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis. These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus. These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.

reprint here and full text here

Science Translational Medicine  22 Feb 2017:
Vol. 9, Issue 378, 
DOI: 10.1126/scitranslmed.aah4680

Featured below: Inhibition of HDAC8 and HDAC9 by microbial short-chain fatty acids breaks immune tolerance of the epidermis to TLR ligands - Science Immunology article


James A. Sanford, Ling-Juan Zhang, Michael R. Williams, Jon A. Gangoiti,
Chun-Ming Huang, Richard L. Gallo

Epidermal keratinocytes participate in immune defense through their capacity to recognize danger, trigger inflammation,
and resist infection. However, normal skin immune function must tolerate contact with an abundant community
of commensal microbes without inflammation. We hypothesized that microbial environmental conditions dictate the
production of molecules that influence epigenetic events and cause keratinocytes to break innate immune tolerance.
Propionibacterium acnes, a commensal skin bacterium, produced the short-chain fatty acids (SCFAs) propionate and
valerate when provided a lipid source in hypoxic growth conditions, and these SCFAs inhibited histone deacetylase
(HDAC) activity. Inhibition of HDAC activity in keratinocytes promoted cytokine expression in response to Toll-like
receptor (TLR) ligands for TLR2 or TLR3. This response was opposite to the action of HDAC inhibition on production
of inflammatory cytokines bymonocytes and involved HDAC8 and HDAC9 because small interfering RNA silencing of
these HDACs recapitulated the activity of SCFAs. Analysis of cytokine expression in mice confirmed the response of the
epidermis where application of SCFA on the skin surface promoted cytokine expression, whereas subcutaneous
administration was inhibitory. These findings show that the products of commensal microbes made under specific
conditions will inhibit HDAC activity and break tolerance of the epidermis to inflammatory stimuli.

Sanford et al., Sci. Immunol. 1, eaah4609 (2016) 28 October 2016

Featured article graphic Science mag Fig5 Final 20161121, pixlr.png

Featured below: Antimicrobial Peptides - NCBI Article

Antimicrobial peptides

Zhang LJ, Gallo RL

Antimicrobial peptides and proteins (AMPs) are a diverse class of naturally occurring molecules that are produced as a first line of defense by all multicellular organisms. These proteins can have broad activity to directly kill bacteria, yeasts, fungi, viruses and even cancer cells. Insects and plants primarily deploy AMPs as an antibiotic to protect against potential pathogenic microbes, but microbes also produce AMPs to defend their environmental niche. In higher eukaryotic organisms, AMPs can also be referred to as 'host defense peptides', emphasizing their additional immunomodulatory activities. These activities are diverse, specific to the type of AMP, and include a variety of cytokine and growth factor-like effects that are relevant to normal immune homeostasis. In some instances, the inappropriate expression of AMPs can also induce autoimmune diseases, thus further highlighting the importance of understanding these molecules and their complex activities. This Primer will provide an update of our current understanding of AMPs.

PMID:
 
26766224
 
DOI:
 
10.1016/j.cub.2015.11.017

 2016 Jan 11;26(1):R14-9. doi: 10.1016/j.cub.2015.11.017.                  ​

Mechanism of AMP function 750X420px.png






AMP in hSkin-JPGpixlr750X753px.jpg




















 PubMed (NCBI) References (link)