title: The lung microbiome of Ugandan HIV-infected pneumonia patients is compositionally and functionally distinct from that of San Franciscan patients.
abstract: Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome was significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population.
authors.affiliation: Division of Gastroenterology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Shoko
authors.initials: S
authors.lastname: Iwai
authors.affiliation: Division of Gastroenterology, University of California San Francisco, San Francisco, California, United States of America; School of Public Health, University of California Berkeley, Berkeley, California, United States of America.
authors.forename: Delphine
authors.initials: D
authors.lastname: Huang
authors.affiliation: HIV/AIDS Division, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Serena
authors.initials: S
authors.lastname: Fong
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Leah G
authors.initials: LG
authors.lastname: Jarlsberg
authors.affiliation: Department of Medicine, Mulago Hospital, Makerere University, Kampala, Uganda.
authors.forename: William
authors.initials: W
authors.lastname: Worodria
authors.affiliation: Department of Medicine, Mulago Hospital, Makerere University, Kampala, Uganda.
authors.forename: Samuel
authors.initials: S
authors.lastname: Yoo
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Adithya
authors.initials: A
authors.lastname: Cattamanchi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: J Lucian
authors.initials: JL
authors.lastname: Davis
authors.affiliation: Department of Medicine, Mulago Hospital, Makerere University, Kampala, Uganda.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kaswabuli
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Segal
authors.affiliation: HIV/AIDS Division, University of California San Francisco, San Francisco, California, United States of America; Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Laurence
authors.initials: L
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015658:HIV Infections / Q000382:microbiology*; D006801:Humans; D008168:Lung / Q000382:microbiology*; D008297:Male; D064307:Microbiota / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D011014:Pneumonia / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D012495:San Francisco; D014454:Uganda; D055815:Young Adult
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20529-33
references.pmid: 18077362
references.citation: Curr Opin Immunol. 2012 Aug;24(4):392-7
references.pmid: 22673877
references.citation: Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):992-6
references.pmid: 8214956
references.citation: Science. 2010 Oct 8;330(6001):204-8
references.pmid: 20736401
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5809-14
references.pmid: 22451929
references.citation: J Clin Microbiol. 2002 Sep;40(9):3449-54
references.pmid: 12202592
references.citation: PLoS One. 2013 May 23;8(5):e63497
references.pmid: 23717435
references.citation: Am J Respir Crit Care Med. 2013 May 15;187(10):1110-7
references.pmid: 23392441
references.citation: Lancet. 2006 Mar 11;367(9513):817-24
references.pmid: 16530575
references.citation: Proc Natl Acad Sci U S A. 2012 May 22;109(21):8334-9
references.pmid: 22566627
references.citation: J Clin Microbiol. 2012 Sep;50(9):2995-3002
references.pmid: 22760045
references.citation: Am J Respir Crit Care Med. 2013 May 15;187(10):1067-75
references.pmid: 23491408
references.citation: OMICS. 2010 Feb;14(1):9-59
references.pmid: 20141328
references.citation: Bioinformatics. 2010 Jun 1;26(11):1463-4
references.pmid: 20395285
references.citation: Sci Transl Med. 2013 Jul 10;5(193):193ra91
references.pmid: 23843452
references.citation: Sci Transl Med. 2012 Sep 12;4(151):151ra124
references.pmid: 22972842
references.citation: J Infect. 1999 May;38(3):176-81
references.pmid: 10424798
references.citation: PLoS Pathog. 2009 May;5(5):e1000423
references.pmid: 19424427
references.citation: Nature. 2013 Aug 8;500(7461):232-6
references.pmid: 23842501
references.citation: PLoS One. 2010 Jun 23;5(6):e11044
references.pmid: 20585638
references.citation: Science. 2011 Jan 21;331(6015):337-41
references.pmid: 21205640
references.citation: J Clin Microbiol. 2007 Jun;45(6):1954-62
references.pmid: 17409203
references.citation: Infect Immun. 2009 Sep;77(9):3661-9
references.pmid: 19564382
references.citation: J Allergy Clin Immunol. 2011 Feb;127(2):372-381.e1-3
references.pmid: 21194740
references.citation: Nat Biotechnol. 2013 Sep;31(9):814-21
references.pmid: 23975157