Susceptibility of bacteria to antimicrobial agents is strongly reduced by t
he formation of complex biofilms. We investigated whether synthetic histati
n analogs with broad-spectrum antibacterial activity in vitro were also act
ive against these complex mixtures of bacteria, as present in saliva and pl
aque. In a simplified model system for dental plaque, hydroxyapatite discs
were placed in a continuous culture system comprised of Streptococcus mutan
s, S. sanguis, S. salivarius, Actinomyces naeslundii, Veillonella parvula,
Fusobacterium nucleatum, and Prevotella intermedia. Ex situ treatment of th
e biofilms formed on these discs with 100 mu g/mL of peptide dhvar4 signifi
cantly reduced facultative anaerobic, total anaerobic, and obligate anaerob
ic Gram-negative counts with 0.8, 0.5, and 0.5 log units, respectively. El
vivo treatment of salivary bacteria gave reductions of 0.4, 0.7, and 1.5 lo
g units, respectively. For ex vivo treatment of plaque bacteria, reductions
of 0.4, 0.4, and 1.4 log units, respectively, were found. In both saliva a
nd plaque samples, obligate anaerobic Gram-negative bacteria were significa
ntly more susceptible to dhvar4 than facultatively anaerobic or anaerobic b
acteria as a whole (p = 0.013 and p = 0.018, for salivary bacteria, and p =
0.021 and p = 0.020 for plaque bacteria, respectively). Although the oral
bacteria are protected by biofilm formation, the synthetic histatin analog
caused a significant reduction of viable counts in a model for oral biofilm
as well as in isolated oral biofilms.