Haemophilus ducreyi SapA contributes to cathelicidin resistance and virulence in humans

Kristy L B Mount, Carisa A. Townsend, Sherri D. Rinker, Xiaoping Gu, Kate R. Fortney, Beth W. Zwickl, Diane Janowicz, Stanley Spinola, Barry Katz, Margaret Bauer

Research output: Contribution to journalArticle

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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 sensitive to antimicrobial peptides (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 35000HPsapA, and compared the percent survival of wild-type 35000HP and 35000HPsapA exposed to several human APs, including α-defensins, β-defensins, and the cathelicidin LL-37. Unlike an H. influenzae sapA mutant, strain 35000HPsapA was not more susceptible to defensins than strain 35000HP was. However, we observed a significant decrease in the survival of strain 35000HPsapA 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 35000HPsapA 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 35000HPsapA 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.

Original languageEnglish
Pages (from-to)1176-1184
Number of pages9
JournalInfection and Immunity
Volume78
Issue number3
DOIs
StatePublished - Mar 2010

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Haemophilus ducreyi
Virulence
Defensins
Peptides
Haemophilus influenzae
Survival
Virulence Factors
Operon
CAP18 lipopolysaccharide-binding protein
Volunteers
Genome

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Mount, K. L. B., Townsend, C. A., Rinker, S. D., Gu, X., Fortney, K. R., Zwickl, B. W., ... Bauer, M. (2010). Haemophilus ducreyi SapA contributes to cathelicidin resistance and virulence in humans. Infection and Immunity, 78(3), 1176-1184. https://doi.org/10.1128/IAI.01014-09

Haemophilus ducreyi SapA contributes to cathelicidin resistance and virulence in humans. / Mount, Kristy L B; Townsend, Carisa A.; Rinker, Sherri D.; Gu, Xiaoping; Fortney, Kate R.; Zwickl, Beth W.; Janowicz, Diane; Spinola, Stanley; Katz, Barry; Bauer, Margaret.

In: Infection and Immunity, Vol. 78, No. 3, 03.2010, p. 1176-1184.

Research output: Contribution to journalArticle

Mount KLB, Townsend CA, Rinker SD, Gu X, Fortney KR, Zwickl BW et al. Haemophilus ducreyi SapA contributes to cathelicidin resistance and virulence in humans. Infection and Immunity. 2010 Mar;78(3):1176-1184. https://doi.org/10.1128/IAI.01014-09
Mount, Kristy L B ; Townsend, Carisa A. ; Rinker, Sherri D. ; Gu, Xiaoping ; Fortney, Kate R. ; Zwickl, Beth W. ; Janowicz, Diane ; Spinola, Stanley ; Katz, Barry ; Bauer, Margaret. / Haemophilus ducreyi SapA contributes to cathelicidin resistance and virulence in humans. In: Infection and Immunity. 2010 ; Vol. 78, No. 3. pp. 1176-1184.
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