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Exploring the Respiratory Mycobiome


Dana Willner, PhD, and Daniel Chambers, MRCP, FRACP, MD
University of Queensland and the Prince Charles Hospital
Brisbane, Queensland, Australia
d.willner@uq.edu.au
Daniel_Chambers@health.qld.gov.au




Fungal infections can lead to serious complications following lung transplantation. Specifically, there is strong evidence that colonization with Aspergillus species is a risk factor for chronic rejection and bronchiolitis obliterans syndrome (BOS) [1, 2]. Aspergillosis has been reported as the most common post-transplant invasive fungal infection in lung transplant recipients, but reports of infections with emergent pathogens such as non-albicans Candida and zygomycoses are increasing [3]. However, how these infections occur as well as the complex interplay between fungi, bacteria, and viruses resident in the respiratory tract is only just beginning to be elucidated.

There has been a recent explosion in studies of microbial communities associated with the human respiratory tract, which is known as the respiratory microbiome. The majority of these have focused on bacteria, exploring the nature and composition of bacterial communities using molecular techniques which do not require cultivation of individual species. Culturing-based approaches provide characterization of individual microbes, while molecular methods allow for the description of entire communities composed of many different organisms. Culture-independent methods generally rely on DNA sequence-based "barcodes," which are short sequences from conserved genetic regions. For example, the ubiquitous and highly conserved 16S ribosomal RNA (rRNA) gene has often been used to identify and discriminate different bacterial species [4]. Recently, exploration of the microbiome has branched out into the exploration of fungal communities, or the mycobiome, using a similar barcoding approach. For fungi, the nuclear ribosomal internal transcribed spacer region (ITS) has been most commonly used for community characterization, and is suitable for discriminating the majority of organisms at the genus and species level [5]. Using ITS profiling, we can explore the full cohort of fungi associated with the human body, otherwise known as the human mycobiome.

While the majority of fungal community profiles generated using amplicon pyrosequencing have been from environmental systems, this technique has been applied to humans, including the respiratory mycobiome, i.e. fungal communities associated with the respiratory tract. Analysis of sputum samples from individuals with and without cystic fibrosis demonstrated that fungal respiratory communities were much more complex than culturing alone would suggest, as over 60% of organisms identified by sequencing were not indicated by cultivation [6]. Individuals with decreased lung function (as measured by FEV1 and FVC) harbored less diverse fungal and bacterial communities, which tended to be dominated by only a small number of organisms [6]. Interestingly, bacterial communities with high abundances of Pseudomonas were more likely to be associated with high abundances of Candida species than with Aspergillus fumigatus [6]. We observed a similar phenomenon in a study of lung transplant patients, in which positive Aspergillus cultures were never isolated in individuals with bacterial communities dominated by Pseudomonas [7].

Charlson et al. performed a similar study simultaneously characterizing bacterial and fungal populations in healthy individuals and transplant recipients, including three individuals who developed BOS [8]. Communities in the upper and lower respiratory tracts were compared by community profiling of oral wash and BAL samples [8]. In the non-transplant population, upper and lower respiratory samples were highly concordant, while some transplant recipients harbored specific lung enriched fungal populations, including Aspergillus species [8].

While it would certainly be true to say that exploration of the pulmonary microbiome is in its infancy, our understanding of the pulmonary mycobiome, particularly in the context of solid organ transplantation, is currently only a twinkle in the eye of mycologists and transplant physicians. Nevertheless it seems likely that important information with direct implications for patient care is highly likely to be forthcoming as the field continues to develop.

Disclosure Statement: The authors have no conflicts of interest to report.


References:

  1. Weigt SS et al. (2009) Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg 9:1903-1911.
  2. Weigt SS et al. (2013) Colonization with small conidia Aspergillus species is associated with bronchiolitis obliterans syndrome: a two-center validation study. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg 13:919-927.
  3. Pappas PG et al. (2010) Invasive Fungal Infections among Organ Transplant Recipients: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 50:1101-1111.
  4. Hugenholtz P, Tyson GW (2008) Microbiology: Metagenomics. Nature 455:481-483.
  5. Schoch CL et al. (2012) Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proc Natl Acad Sci U S A 109:6241-6246.
  6. Delhaes L et al. (2012) The airway microbiota in cystic fibrosis: a complex fungal and bacterial community-implications for therapeutic management. PloS One 7:e36313.
  7. Willner DL et al. (2013) Reestablishment of Recipient-associated Microbiota in the Lung Allograft Is Linked to Reduced Risk of Bronchiolitis Obliterans Syndrome. Am J Respir Crit Care Med 187:640-647.
  8. Charlson ES et al. (2012) Lung-enriched Organisms and Aberrant Bacterial and Fungal Respiratory Microbiota following Lung Transplant. Am J Respir Crit Care Med. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22798321 [Accessed August 4, 2012].



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