Document Detail


Widespread colonization of the lung by Tropheryma whipplei in HIV infection.
MedLine Citation:
PMID:  23392441     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Lung infections caused by opportunistic or virulent pathogens are a principal cause of morbidity and mortality in HIV infection. 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 lung-derived 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.
Authors:
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 Lynch; Laurence Huang; George M Weinstock; Kenneth S Knox; Homer Twigg; Alison Morris; Elodie Ghedin; Frederic D Bushman; Ronald G Collman; Rob Knight; Andrew P Fontenot;
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  187     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-16     Completed Date:  2013-07-18     Revised Date:  2014-04-17    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1110-7     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Cohort Studies
HIV Infections / complications*
Humans
Longitudinal Studies
Lung / microbiology*
Tropheryma*
Whipple Disease / complications*,  microbiology*
Grant Support
ID/Acronym/Agency:
AI045008/AI/NIAID NIH HHS; AI075410/AI/NIAID NIH HHS; AI31834/AI/NIAID NIH HHS; AI34989/AI/NIAID NIH HHS; AI34993/AI/NIAID NIH HHS; AI34994/AI/NIAID NIH HHS; AI35004/AI/NIAID NIH HHS; AI35039/AI/NIAID NIH HHS; AI35040/AI/NIAID NIH HHS; AI35041/AI/NIAID NIH HHS; AI35042/AI/NIAID NIH HHS; AI35043/AI/NIAID NIH HHS; DK090285/DK/NIDDK NIH HHS; HD32632/HD/NICHD NIH HHS; HL087713/HL/NHLBI NIH HHS; HL090335/HL/NHLBI NIH HHS; HL090339/HL/NHLBI NIH HHS; HL098957/HL/NHLBI NIH HHS; HL098960/HL/NHLBI NIH HHS; HL098961/HL/NHLBI NIH HHS; HL098962/HL/NHLBI NIH HHS; HL098964/HL/NHLBI NIH HHS; HL102245/HL/NHLBI NIH HHS; HL98996/HL/NHLBI NIH HHS; K01 DK090285/DK/NIDDK NIH HHS; U01AI42590/AI/NIAID NIH HHS; UL1 RR024131/RR/NCRR NIH HHS; UL1 RR024153/RR/NCRR NIH HHS; UL1 TR000005/TR/NCATS NIH HHS; UL1 TR000154/TR/NCATS NIH HHS; UL1-RR025005/RR/NCRR NIH HHS; UL1TR000005/TR/NCATS NIH HHS

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