Degradation of antimicrobial histatin-variant peptides in Staphylococcus aureus and Streptococcus mutans.
Histidine-free variants of salivary histatin 5 have a broad antimicrobial activity against various bacteria. In relation to a possible therapeutic application, we were interested in the susceptibility of these small peptides (14 amino acids long) to microbial proteinases and whether this affects their antimicrobial activity. Analyses by SDS-PAGE of supernatants of peptide-bacteria incubation showed a reduction in protein bands within 15 minutes' incubation, as a result of cellular internalization. Degradation products of dhvar1 and dhvar2 appeared within one hour in the supernatants of Streptococcus mutans and Staphylococcus aureus. In contrast, the variants dhvar3 and dhvar4 were more resistant to degradation under the same conditions. MALDI-TOF analyses identified cleavage of dhvar1 and dhvar2 at Glu(6). The N-terminal peptide part (1-6) of dhvar1 and 2 showed no bactericidal activity, while peptide fragment (7-14) showed a highly reduced bactericidal activity.
Groenink
J
J
Department of Dental Basic Sciences, Section of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. j.groenink.obc.acta@med.vu.nl
Ruissen
A L A
AL
Lowies
D
D
van 't Hof
W
W
Veerman
E C I
EC
Nieuw Amerongen
A V
AV
D000900:Anti-Bacterial Agents / Q000145:classification / Q000378:metabolism*; D015891:Cystatins / Q000145:classification / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000145:classification / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D054808:Histatins; D006801:Humans; D010446:Peptide Fragments / Q000145:classification / Q000378:metabolism; D011480:Protease Inhibitors / Q000145:classification / Q000378:metabolism*; D055333:Salivary Cystatins; D012471:Salivary Proteins and Peptides / Q000145:classification / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*; D013295:Streptococcus mutans / Q000378:metabolism*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; C068075:HTN3 protein, human; D054808:Histatins; D010446:Peptide Fragments; D011480:Protease Inhibitors; D055333:Salivary Cystatins; D012471:Salivary Proteins and Peptides