Haemophilus ducreyi seeks alternative carbon sources and adapts to nutrient stress and anaerobiosis during experimental infection of human volunteers

Dharanesh Gangaiah, Xinjun Zhang, Beth Baker, Kate R. Fortney, Hongyu Gao, Concerta L. Holley, Robert S. Munson, Yunlong Liu, Stanley Spinola

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Haemophilus ducreyi causes the sexually transmitted disease chancroid in adults and cutaneous ulcers in children. In humans, H. ducreyi resides in an abscess and must adapt to a variety of stresses. Previous studies (D. Gangaiah, M. Labandeira-Rey, X. Zhang, K. R. Fortney, S. Ellinger, B. Zwickl, B. Baker, Y. Liu, D. M. Janowicz, B. P. Katz, C. A. Brautigam, R. S. Munson, Jr., E. J. Hansen, and S. M. Spinola, mBio 5:e01081-13, 2014, http://dx.doi.org/10.1128/mBio.01081-13) suggested that H. ducreyi encounters growth conditions in human lesions resembling those found in stationary phase. However, how H. ducreyi transcriptionally responds to stress during human infection is unknown. Here, we determined the H. ducreyi transcriptome in biopsy specimens of human lesions and compared it to the transcriptomes of bacteria grown to mid-log, transition, and stationary phases. Multidimensional scaling showed that the in vivo transcriptome is distinct from those of in vitro growth. Compared to the inoculum (mid-log-phase bacteria), H. ducreyi harvested from pustules differentially expressed ~93 genes, of which 62 were upregulated. The upregulated genes encode homologs of proteins involved in nutrient transport, alternative carbon pathways (L-ascorbate utilization and metabolism), growth arrest response, heat shock response, DNA recombination, and anaerobiosis. H. ducreyi upregulated few genes (hgbA, flp-tad, and lspB-lspA2) encoding virulence determinants required for human infection. Most genes regulated by CpxRA, RpoE, Hfq, (p)ppGpp, and DksA, which control the expression of virulence determinants and adaptation to a variety of stresses, were not differentially expressed in vivo, suggesting that these systems are cycling on and off during infection. Taken together, these data suggest that the in vivo transcriptome is distinct from those of in vitro growth and that adaptation to nutrient stress and anaerobiosis is crucial for H. ducreyi survival in humans.

Original languageEnglish (US)
Pages (from-to)1514-1525
Number of pages12
JournalInfection and Immunity
Volume84
Issue number5
DOIs
StatePublished - May 1 2016

Fingerprint

Haemophilus ducreyi
Anaerobiosis
Volunteers
Carbon
Food
Infection
Transcriptome
Growth
Genes
Virulence
Chancroid
Skin Ulcer
Bacteria
Heat-Shock Response
Phase Transition
Sexually Transmitted Diseases
Abscess
Genetic Recombination
Biopsy

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Haemophilus ducreyi seeks alternative carbon sources and adapts to nutrient stress and anaerobiosis during experimental infection of human volunteers. / Gangaiah, Dharanesh; Zhang, Xinjun; Baker, Beth; Fortney, Kate R.; Gao, Hongyu; Holley, Concerta L.; Munson, Robert S.; Liu, Yunlong; Spinola, Stanley.

In: Infection and Immunity, Vol. 84, No. 5, 01.05.2016, p. 1514-1525.

Research output: Contribution to journalArticle

Gangaiah, Dharanesh ; Zhang, Xinjun ; Baker, Beth ; Fortney, Kate R. ; Gao, Hongyu ; Holley, Concerta L. ; Munson, Robert S. ; Liu, Yunlong ; Spinola, Stanley. / Haemophilus ducreyi seeks alternative carbon sources and adapts to nutrient stress and anaerobiosis during experimental infection of human volunteers. In: Infection and Immunity. 2016 ; Vol. 84, No. 5. pp. 1514-1525.
@article{972da23fbdcf4317a7eb50995216165b,
title = "Haemophilus ducreyi seeks alternative carbon sources and adapts to nutrient stress and anaerobiosis during experimental infection of human volunteers",
abstract = "Haemophilus ducreyi causes the sexually transmitted disease chancroid in adults and cutaneous ulcers in children. In humans, H. ducreyi resides in an abscess and must adapt to a variety of stresses. Previous studies (D. Gangaiah, M. Labandeira-Rey, X. Zhang, K. R. Fortney, S. Ellinger, B. Zwickl, B. Baker, Y. Liu, D. M. Janowicz, B. P. Katz, C. A. Brautigam, R. S. Munson, Jr., E. J. Hansen, and S. M. Spinola, mBio 5:e01081-13, 2014, http://dx.doi.org/10.1128/mBio.01081-13) suggested that H. ducreyi encounters growth conditions in human lesions resembling those found in stationary phase. However, how H. ducreyi transcriptionally responds to stress during human infection is unknown. Here, we determined the H. ducreyi transcriptome in biopsy specimens of human lesions and compared it to the transcriptomes of bacteria grown to mid-log, transition, and stationary phases. Multidimensional scaling showed that the in vivo transcriptome is distinct from those of in vitro growth. Compared to the inoculum (mid-log-phase bacteria), H. ducreyi harvested from pustules differentially expressed ~93 genes, of which 62 were upregulated. The upregulated genes encode homologs of proteins involved in nutrient transport, alternative carbon pathways (L-ascorbate utilization and metabolism), growth arrest response, heat shock response, DNA recombination, and anaerobiosis. H. ducreyi upregulated few genes (hgbA, flp-tad, and lspB-lspA2) encoding virulence determinants required for human infection. Most genes regulated by CpxRA, RpoE, Hfq, (p)ppGpp, and DksA, which control the expression of virulence determinants and adaptation to a variety of stresses, were not differentially expressed in vivo, suggesting that these systems are cycling on and off during infection. Taken together, these data suggest that the in vivo transcriptome is distinct from those of in vitro growth and that adaptation to nutrient stress and anaerobiosis is crucial for H. ducreyi survival in humans.",
author = "Dharanesh Gangaiah and Xinjun Zhang and Beth Baker and Fortney, {Kate R.} and Hongyu Gao and Holley, {Concerta L.} and Munson, {Robert S.} and Yunlong Liu and Stanley Spinola",
year = "2016",
month = "5",
day = "1",
doi = "10.1128/IAI.00048-16",
language = "English (US)",
volume = "84",
pages = "1514--1525",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - Haemophilus ducreyi seeks alternative carbon sources and adapts to nutrient stress and anaerobiosis during experimental infection of human volunteers

AU - Gangaiah, Dharanesh

AU - Zhang, Xinjun

AU - Baker, Beth

AU - Fortney, Kate R.

AU - Gao, Hongyu

AU - Holley, Concerta L.

AU - Munson, Robert S.

AU - Liu, Yunlong

AU - Spinola, Stanley

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Haemophilus ducreyi causes the sexually transmitted disease chancroid in adults and cutaneous ulcers in children. In humans, H. ducreyi resides in an abscess and must adapt to a variety of stresses. Previous studies (D. Gangaiah, M. Labandeira-Rey, X. Zhang, K. R. Fortney, S. Ellinger, B. Zwickl, B. Baker, Y. Liu, D. M. Janowicz, B. P. Katz, C. A. Brautigam, R. S. Munson, Jr., E. J. Hansen, and S. M. Spinola, mBio 5:e01081-13, 2014, http://dx.doi.org/10.1128/mBio.01081-13) suggested that H. ducreyi encounters growth conditions in human lesions resembling those found in stationary phase. However, how H. ducreyi transcriptionally responds to stress during human infection is unknown. Here, we determined the H. ducreyi transcriptome in biopsy specimens of human lesions and compared it to the transcriptomes of bacteria grown to mid-log, transition, and stationary phases. Multidimensional scaling showed that the in vivo transcriptome is distinct from those of in vitro growth. Compared to the inoculum (mid-log-phase bacteria), H. ducreyi harvested from pustules differentially expressed ~93 genes, of which 62 were upregulated. The upregulated genes encode homologs of proteins involved in nutrient transport, alternative carbon pathways (L-ascorbate utilization and metabolism), growth arrest response, heat shock response, DNA recombination, and anaerobiosis. H. ducreyi upregulated few genes (hgbA, flp-tad, and lspB-lspA2) encoding virulence determinants required for human infection. Most genes regulated by CpxRA, RpoE, Hfq, (p)ppGpp, and DksA, which control the expression of virulence determinants and adaptation to a variety of stresses, were not differentially expressed in vivo, suggesting that these systems are cycling on and off during infection. Taken together, these data suggest that the in vivo transcriptome is distinct from those of in vitro growth and that adaptation to nutrient stress and anaerobiosis is crucial for H. ducreyi survival in humans.

AB - Haemophilus ducreyi causes the sexually transmitted disease chancroid in adults and cutaneous ulcers in children. In humans, H. ducreyi resides in an abscess and must adapt to a variety of stresses. Previous studies (D. Gangaiah, M. Labandeira-Rey, X. Zhang, K. R. Fortney, S. Ellinger, B. Zwickl, B. Baker, Y. Liu, D. M. Janowicz, B. P. Katz, C. A. Brautigam, R. S. Munson, Jr., E. J. Hansen, and S. M. Spinola, mBio 5:e01081-13, 2014, http://dx.doi.org/10.1128/mBio.01081-13) suggested that H. ducreyi encounters growth conditions in human lesions resembling those found in stationary phase. However, how H. ducreyi transcriptionally responds to stress during human infection is unknown. Here, we determined the H. ducreyi transcriptome in biopsy specimens of human lesions and compared it to the transcriptomes of bacteria grown to mid-log, transition, and stationary phases. Multidimensional scaling showed that the in vivo transcriptome is distinct from those of in vitro growth. Compared to the inoculum (mid-log-phase bacteria), H. ducreyi harvested from pustules differentially expressed ~93 genes, of which 62 were upregulated. The upregulated genes encode homologs of proteins involved in nutrient transport, alternative carbon pathways (L-ascorbate utilization and metabolism), growth arrest response, heat shock response, DNA recombination, and anaerobiosis. H. ducreyi upregulated few genes (hgbA, flp-tad, and lspB-lspA2) encoding virulence determinants required for human infection. Most genes regulated by CpxRA, RpoE, Hfq, (p)ppGpp, and DksA, which control the expression of virulence determinants and adaptation to a variety of stresses, were not differentially expressed in vivo, suggesting that these systems are cycling on and off during infection. Taken together, these data suggest that the in vivo transcriptome is distinct from those of in vitro growth and that adaptation to nutrient stress and anaerobiosis is crucial for H. ducreyi survival in humans.

UR - http://www.scopus.com/inward/record.url?scp=84965147690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84965147690&partnerID=8YFLogxK

U2 - 10.1128/IAI.00048-16

DO - 10.1128/IAI.00048-16

M3 - Article

C2 - 26930707

AN - SCOPUS:84965147690

VL - 84

SP - 1514

EP - 1525

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 5

ER -