Expression of Antimicrobial Peptides in the Normal and Involved Skin of Patients with Infective Cellulitis

Stryjewski, Martín E.; Hall, Russell P.; Chu, Vivian H.; Kanafani, Zeina A.; O’Riordan, William; Weinstock, Michael S.; Stienecker, R. Scott; Streilein, Robert D.; Dorschner, Robert A.; Fowler, Vance G.; Corey, G. Ralph; Gallo, Richard L.

doi:10.1086/522630

Cited by 19 publications

(13 citation statements)

References 15 publications

(26 reference statements)

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“…These findings confirm results from various in vitro studies of cultured keratinocytes exposed to live and heat-inactivated S. aureus (5,13) or to cell wall components of Gram-positive bacteria (12,23) but are contradictory to results from one in vitro study that found GAS to be a poor inducer of HBD-2 (5). Our study adds to the evidence from other in vivo studies demonstrating a strong induction of HBD-2 by Gram-positive bacterial infection (16,24). Our findings, in part presented earlier for a subgroup of patients with S. aureus skin infection (26), are the first, to our knowledge, to demonstrate induction of HBD-3 in response to Gram-positive skin infection in vivo.…”

Section: Discussionsupporting

confidence: 82%

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Severity of Staphylococcus aureus Infection of the Skin Is Associated with Inducibility of Human β-Defensin 3 but Not Human β-Defensin 2

et al. 2010

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Gram-positive bacteria are the predominant cause of skin infections. Antimicrobial peptides (AMPs) are believed to be of major importance in skin's innate defense against these pathogens. This study aimed at providing clinical evidence for the contribution of AMP inducibility to determining the severity of Grampositive skin infection. Using real-time PCR, we determined the induction of human ␤-defensin 2 (HBD-2), HBD-3, and RNase 7 by comparing healthy and lesional mRNA levels in 32 patients with Gram-positive skin infection. We then examined whether AMP induction differed by disease severity, as measured by number of recurrences and need for surgical drainage in patients with Staphylococcus aureus-positive lesions. We found that HBD-2 and -3, but not RNase 7, mRNA expression was highly induced by Gram-positive bacterial infection in otherwise healthy skin. Less induction of HBD-3, but not HBD-2, was associated with more-severe S. aureus skin infection: HBD-3 mRNA levels were 11.4 times lower in patients with more than 6 recurrences (P ‫؍‬ 0.01) and 8.8 times lower in patients reporting surgical drainage (P ‫؍‬ 0.01) than in the respective baseline groups. This suggests that inducibility of HBD-3 influences the severity of Gram-positive skin infection in vivo. The physiological function of HBD-2 induction in this context remains unclear.

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Section: Discussionsupporting

confidence: 82%

“…In fact, it has been shown for HBD-2 that a lesion can cause upregulation even in nonaffected skin via systemic release of inflammatory mediators (24). In our study, such an effect may be present to some degree for HBD-2, as expression in healthy skin was highest in patients with more than 6 recurrences.…”

Section: Discussionsupporting

confidence: 46%

Severity of Staphylococcus aureus Infection of the Skin Is Associated with Inducibility of Human β-Defensin 3 but Not Human β-Defensin 2

et al. 2010

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“…A strong relationship has been demonstrated in human patients affected by different inflammatory diseases, such as psoriasis and atopic dermatitis, 28,29 and a marked difference in BD expression in these two diseases (lower in atopy and higher in psoriasis) is probably due to the different immunological patterns that characterize these two inflammatory diseases 30–32 . Recent studies have suggested that the differential expression of AMPs can underlie higher susceptibility to bacterial infection in atopic individuals compared with patients with psoriasis 3,6,23,29–33 …”

Section: Discussionmentioning

confidence: 99%

Expression and distribution of antimicrobial peptides in the skin of healthy beagles

Santoro

Bunick

Graves

et al. 2011

Veterinary Dermatology

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Antimicrobial peptides (AMPs) are small proteins involved in defense against pathogenic organisms. Defensins and cathelicidin are the most frequently studied human AMPs. Our goals were to determine the distribution of AMPs and evaluate their mRNA expression in normal canine skin. Skin biopsies were taken from six healthy beagles. The relative transcript level of canine cathelicidin (cCath) and β-defensin (cBD)-1, cBD2 and cBD3 mRNA was quantified using quantitative real-time polymerase chain reaction. Indirect immunofluorescence (IIF), using polyclonal antibodies against cBD2, cBD3 and cCath, was used to evaluate protein localization in the skin of healthy dogs. The Pfaffl method, using experimentally determined primer efficiencies of amplification, was used to determine the expression level of cCath, cBD1 and cDB3 relative to cDB2. The levels of cCath, cBD3 and cBD1 mRNA were 358, 296 and 177 times higher than those of cBD2, respectively. Using IIF, cBD2 and cBD3 protein fluorescence was detected in all layers of the epidermis, whereas cCath was detected predominantly in the stratum granulosum and corneum. In addition, antimicrobial peptide detection was limited to the infundibular portion of the pilosebaceous units. We have validated useful methods to evaluate AMPs in canine skin. Further studies are needed to compare AMP expression in healthy dogs with that of dogs with inflammatory skin conditions.

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“…The most popular and main-stream areas of research are new antimicrobial therapeutics [29]. However, alternative therapeutic options are also under investigation, to name: antimicrobial natural compounds [30,31], cationic antimicrobial peptides [32], the use of protection strategy to biofilm formation [33,34] or bacteriophage-based approaches [35,36]. Among the listed, photodynamic inactivation (PDI) of S. aureus is also a promising option.…”

Section: Discussionmentioning

confidence: 99%

Superoxide dismutase is upregulated in Staphylococcus aureus following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment

et al. 2010

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BackgroundStaphylococcus aureus, a major human pathogen causes a wide range of disease syndromes. The most dangerous are methicillin-resistant S. aureus (MRSA) strains, resistant not only to all β-lactam antibiotics but also to other antimicrobials. An alarming increase in antibiotic resistance spreading among pathogenic bacteria inclines to search for alternative therapeutic options, for which resistance can not be developed easily. Among others, photodynamic inactivation (PDI) of S. aureus is a promising option. Photodynamic inactivation is based on a concept that a non toxic chemical, called a photosensitizer upon excitation with light of an appropriate wavelength is activated. As a consequence singlet oxygen and other reactive oxygen species (e.g. superoxide anion) are produced, which are responsible for the cytotoxic effect towards bacterial cells. As strain-dependence in photodynamic inactivation of S. aureus was observed, determination of the molecular marker(s) underlying the mechanism of the bacterial response to PDI treatment would be of great clinical importance. We examined the role of superoxide dismutases (Sod) in photodynamic inactivation of S. aureus as enzymes responsible for oxidative stress resistance.ResultsThe effectiveness of photodynamic inactivation towards S. aureus and its Sod isogenic mutants deprived of either of the two superoxide dismutase activities, namely SodA or SodM or both of them showed similar results, regardless of the Sod status in TSB medium. On the contrary, in the CL medium (without Mn++ ions) the double SodAM mutant was highly susceptible to photodynamic inactivation. Among 8 clinical isolates of S. aureus analyzed (4 MRSA and 4 MSSA), strains highly resistant and strains highly vulnerable to photodynamic inactivation were noticed. We observed that Sod activity as well as sodA and sodM transcript level increases after protoporphyrin IX-based photodynamic treatment but only in PDI-sensitive strains.ConclusionsWe confirmed that porphyrin-based photokilling efficacy is a strain-dependent phenomenon. We showed that oxidative stress sensitivity caused by the lack of both Sod enzymes can be relieved in the presence of Mn ions and partially in the presence of Fe ions. The fact that Sod activity increase is observed only in PDI-susceptible cells emphasizes that this is probably not a direct factor affecting S. aureus vulnerability to porphyrin-based PDI.

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Expression of Antimicrobial Peptides in the Normal and Involved Skin of Patients with Infective Cellulitis

Cited by 19 publications

References 15 publications

Severity of Staphylococcus aureus Infection of the Skin Is Associated with Inducibility of Human β-Defensin 3 but Not Human β-Defensin 2

Severity of Staphylococcus aureus Infection of the Skin Is Associated with Inducibility of Human β-Defensin 3 but Not Human β-Defensin 2

Expression and distribution of antimicrobial peptides in the skin of healthy beagles

Superoxide dismutase is upregulated in Staphylococcus aureus following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment

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