Activity of histone H1.2 in infected burn wounds.
OBJECTIVE
Infections with multidrug-resistant microorganisms (e.g. Pseudomonas aeruginosa and Staphylococcus aureus) cause immense complications in wound care and in the treatment of immunosuppressed patients. Like most antimicrobial peptides, histones are relatively small polycationic proteins located in each eukaryotic nucleus, which naturally supercoil DNA. The aim of this study was to investigate the in vitro and in vivo activity of histone H1.2 in infected burn wounds and its potential toxicity.


METHODS
To characterize the antimicrobial properties of histone H1.2 against potential causative organisms of burn wound infections, the in vitro radial diffusion assay and modified NCCLS microbroth dilution MIC assay were carried out. Haemolytic and cytotoxic properties were determined in human red blood cells and primary human keratinocytes. In vivo antimicrobial activity was tested in an infected rat burn model with P. aeruginosa (ATCC 27853). All results were compared with the naturally occurring broad-spectrum antimicrobial peptide protegrin-1 and with antibiotics clinically used against the corresponding bacteria.


RESULTS
Human histone H1.2 exerted good antimicrobial activity against all tested microorganisms without significant haemolytic activity. Surprisingly, histone H1.2 showed cytotoxicity with an LD50 of 7.91 mg/L in primary human keratinocytes. The in vivo burn model data revealed a significant three-fold higher reduction in bacterial counts within 4 h compared with carrier control.


CONCLUSIONS
These findings indicate that histone H1.2 is a potential candidate for use as a local and, because of its low haemolytic activity, systemic antimicrobial agent. However, further investigations are needed to specify the cytotoxicity and the dose-response relationship for histone H1.2.
Jacobsen
F
F
Department for Plastic Surgery, BG University Hospital Bergmannsheil, University Bochum, Buerkle-de-la-Camp Platz 1, 44789 Bochum, Germany.
Baraniskin
A
A
Mertens
J
J
Mittler
D
D
Mohammadi-Tabrisi
A
A
Schubert
S
S
Soltau
M
M
Lehnhardt
M
M
Behnke
B
B
Gatermann
S
S
Steinau
H U
HU
Steinstraesser
L
L
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001419:Bacteria / Q000187:drug effects; D002056:Burns / Q000150:complications*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006657:Histones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011506:Proteins / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D012867:Skin / Q000166:cytology; D018675:Toxicity Tests; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
D023181:Antimicrobial Cationic Peptides; D006657:Histones; D011506:Proteins; C094880:protegrin-1