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 M Spinola

Journal: Infection and immunity 2017;84(5):1514-1525

PMID: 26930707

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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. MunsonJr, 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.

Address: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.; The Center for Microbial Pathogenesis in the Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA.; The Center for Microbial Pathogenesis in the Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA [email protected].; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Center for Immunobiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

DOI: 10.1128/IAI.00048-16

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MeSH Terms: Adaptation, Physiological, Adult, Anaerobiosis, Biopsy, Carbon, Chancroid, Female, Gene Expression Profiling, Haemophilus ducreyi, Healthy Volunteers, Humans, Male, Stress, Physiological