Carbon storage regulator a contributes to the virulence of haemophilus ducreyi in humans by multiple mechanisms

Dharanesh Gangaiah, Wei Li, Kate R. Fortney, Diane Janowicz, Sheila Ellinger, Beth Zwickl, Barry Katz, Stanley Spinola

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The carbon storage regulator A (CsrA) controls a wide variety of bacterial processes, including metabolism, adherence, stress responses, and virulence. Haemophilus ducreyi, the causative agent of chancroid, harbors a homolog of csrA. Here, we generated an unmarked, in-frame deletion mutant of csrA to assess its contribution to H. ducreyi pathogenesis. In human inoculation experiments, the csrA mutant was partially attenuated for pustule formation compared to its parent. Deletion of csrA resulted in decreased adherence of H. ducreyi to human foreskin fibroblasts (HFF); Flp1 and Flp2, the determinants of H. ducreyi adherence to HFF cells, were downregulated in the csrA mutant. Compared to its parent, the csrA mutant had a significantly reduced ability to tolerate oxidative stress and heat shock. The enhanced sensitivity of the mutant to oxidative stress was more pronounced in bacteria grown to stationary phase compared to that in bacteria grown to mid-log phase. The csrA mutant also had a significant survival defect within human macrophages when the bacteria were grown to stationary phase but not to mid-log phase. Complementation in trans partially or fully restored the mutant phenotypes. These data suggest that CsrA contributes to virulence by multiple mechanisms and that these contributions may be more profound in bacterial cell populations that are not rapidly dividing in the human host.

Original languageEnglish
Pages (from-to)608-617
Number of pages10
JournalInfection and Immunity
Volume81
Issue number2
DOIs
StatePublished - Feb 2013

Fingerprint

Haemophilus ducreyi
Virulence
Carbon
Foreskin
Bacteria
Oxidative Stress
Bacterial Physiological Phenomena
Fibroblasts
Chancroid
Shock
Down-Regulation
Hot Temperature
Macrophages
Phenotype
Survival
Population

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Carbon storage regulator a contributes to the virulence of haemophilus ducreyi in humans by multiple mechanisms. / Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R.; Janowicz, Diane; Ellinger, Sheila; Zwickl, Beth; Katz, Barry; Spinola, Stanley.

In: Infection and Immunity, Vol. 81, No. 2, 02.2013, p. 608-617.

Research output: Contribution to journalArticle

Gangaiah, Dharanesh ; Li, Wei ; Fortney, Kate R. ; Janowicz, Diane ; Ellinger, Sheila ; Zwickl, Beth ; Katz, Barry ; Spinola, Stanley. / Carbon storage regulator a contributes to the virulence of haemophilus ducreyi in humans by multiple mechanisms. In: Infection and Immunity. 2013 ; Vol. 81, No. 2. pp. 608-617.
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