Widespread colonization of the lung by Tropheryma whipplei in HIV infection

Catherine Lozupone, Adela Cota-Gomez, Brent E. Palmer, Derek J. Linderman, Emily S. Charlson, Erica Sodergren, Makedonka Mitreva, Sahar Abubucker, John Martin, Guohui Yao, Thomas B. Campbell, Sonia C. Flores, Gail Ackerman, Jesse Stombaugh, Luke Ursell, James M. Beck, Jeffrey L. Curtis, Vincent B. Young, Susan V. Lynchv, Laurence HuangGeorge M. Weinstock, Kenneth S. Knox, Homer Twigg, Alison Morris, Elodie Ghedin, Frederic D. Bushman, Ronald G. Collman, Rob Knight, Andrew P. Fontenot

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Rationale: Lung infections caused by opportunistic or virulent pathogensare a principal cause of morbidityandmortality in HIVinfection. It is unknown whether HIV infection leads to changes in basal lung microflora, which may contribute to chronic pulmonary complications that increasingly are being recognized in individuals infected with HIV. Objectives: To determine whether the immunodeficiency associated with HIV infection resulted in alteration of the lung microbiota. Methods:We used 16S ribosomal RNA targeted pyrosequencing and shotgun metagenomic sequencing to analyze bacterial gene sequences in bronchoalveolar lavage (BAL) and mouths of 82 HIV-positive and 77 HIV-negative subjects. Measurements and Main Results: Sequences representing Tropheryma whipplei, the etiologic agent of Whipple's disease, were significantly more frequent in BAL of HIV-positive compared with HIV-negative individuals. T. whipplei dominated the community (>50% of sequence reads) in 11 HIV-positive subjects, but only 1 HIV-negative individual (13.4 versus 1.3%; P = 0.0018). In 30 HIV-positive individuals sampled longitudinally, antiretroviral therapy resulted in a significantly reduced relative abundance of T. whipplei in the lung. Shotgun metagenomic sequencing was performed on eight BAL samples dominated by T. whipplei 16S ribosomal RNA. Whole genome assembly of pooled reads showed that uncultured lungderived T. whipplei had similar gene content to two isolates obtained from subjects with Whipple's disease. Conclusions: Asymptomatic subjects with HIV infection have unexpected colonization of the lung by T. whipplei, which is reduced by effective antiretroviral therapy and merits further study for a potential pathogenic role in chronic pulmonary complications of HIV infection.

Original languageEnglish (US)
Pages (from-to)1110-1117
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume187
Issue number10
DOIs
StatePublished - May 15 2013

Keywords

  • 16S ribosomal RNA
  • Bronchoalveolar lavage
  • Human
  • Metagenome
  • Microbiome

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Fingerprint Dive into the research topics of 'Widespread colonization of the lung by Tropheryma whipplei in HIV infection'. Together they form a unique fingerprint.

  • Cite this

    Lozupone, C., Cota-Gomez, A., Palmer, B. E., Linderman, D. J., Charlson, E. S., Sodergren, E., Mitreva, M., Abubucker, S., Martin, J., Yao, G., Campbell, T. B., Flores, S. C., Ackerman, G., Stombaugh, J., Ursell, L., Beck, J. M., Curtis, J. L., Young, V. B., Lynchv, S. V., ... Fontenot, A. P. (2013). Widespread colonization of the lung by Tropheryma whipplei in HIV infection. American journal of respiratory and critical care medicine, 187(10), 1110-1117. https://doi.org/10.1164/rccm.201211-2145OC