Affiliation:
1. Departments of Microbiology and Immunology
2. Medicine
3. Pathology and Laboratory Medicine
4. Center for Immunobiology, Indiana University School of Medicine, 635 Barnhill Drive, Room MS 420, Indianapolis, Indiana 46202-5124
Abstract
ABSTRACT
Haemophilus ducreyi
is an extracellular pathogen of human epithelial surfaces that resists human antimicrobial peptides (APs). The organism's genome contains homologs of genes
s
ensitive to
a
ntimicrobial
p
eptides (
sap
operon) in nontypeable
Haemophilus influenzae
. In this study, we characterized the
sap
-containing loci of
H. ducreyi
35000HP and demonstrated that
sapA
is expressed in broth cultures and
H. ducreyi
-infected tissue;
sapA
is also conserved among both class I and class II
H. ducreyi
strains. We constructed a nonpolar
sapA
mutant of
H. ducreyi
35000HP, designated 35000HP
sapA
, and compared the percent survival of wild-type 35000HP and 35000HP
sapA
exposed to several human APs, including α-defensins, β-defensins, and the cathelicidin LL-37. Unlike an
H. influenzae sapA
mutant, strain 35000HP
sapA
was not more susceptible to defensins than strain 35000HP was. However, we observed a significant decrease in the survival of strain 35000HP
sapA
after exposure to LL-37, which was complemented by introducing
sapA
in
trans
. Thus, the Sap transporter plays a role in resistance of
H. ducreyi
to LL-37. We next compared mutant strain 35000HP
sapA
with strain 35000HP for their ability to cause disease in human volunteers. Although both strains caused papules to form at similar rates, the pustule formation rate at sites inoculated with 35000HP
sapA
was significantly lower than that of sites inoculated with 35000HP (33.3% versus 66.7%;
P
= 0.007). Together, these data establish that SapA acts as a virulence factor and as one mechanism for
H. ducreyi
to resist killing by antimicrobial peptides. To our knowledge, this is the first demonstration that an antimicrobial peptide resistance mechanism contributes to bacterial virulence in humans.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
36 articles.
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