Urinary microbiome of kidney transplant patients reveals dysbiosis with potential for antibiotic resistance.
Recent studies have established that a complex community of microbes colonize the human urinary tract; however, their role in kidney transplant patients treated with prophylactic antibiotics remains poorly investigated. Our aim was to investigate the urinary microbiome of kidney transplant recipients. Urine samples from 21 patients after kidney transplantation and 8 healthy controls were collected. All patients received prophylactic treatment with the antibiotic combination trimethoprim-sulfamethoxazole. Metagenomic DNA was isolated from urine samples, sequenced using shotgun sequencing approach on Illumina HiSeq 2000 platform, and analyzed for microbial taxonomic and functional annotations. Our results demonstrate that the urine microbiome of kidney transplants was markedly different at all taxonomic levels from phyla to species, had decreased microbial diversity, and increased abundance of potentially pathogenic species compared with healthy controls. Specifically, at the phylum level, we detected a significant decrease in Actinobacteria and increase in Firmicutes due to increases in Enterococcus faecalis. In addition, there was an increase in the Proteobacteria due to increases in Escherichia coli. Analysis of predicted functions of the urinary metagenome revealed increased abundance of enzymes in the folate pathway including dihydrofolate synthase that are not inhibited by trimethoprim-sulfamethoxazole, but can augment folate metabolism. This report characterizes the urinary microbiome of kidney transplants using shotgun metagenomics approach. Our results indicate that the urinary microbiota may be modified in the context of prophylactic antibiotics, indicating that a therapeutic intervention may shift the urinary microbiota to select bacterial species with increased resistance to antibiotics. The evaluation and development of optimal prophylactic regimens that do not promote antibiotic resistance is an important future goal.
Department of Medicine, University of Illinois, Chicago, Ill.
Asha
A
Rani
Department of Medicine, University of Illinois, Chicago, Ill.
Ravi
R
Ranjan
Department of Medicine, University of Illinois, Chicago, Ill.
Halvor S
HS
McGee
Department of Medicine, University of Illinois, Chicago, Ill.
Kalista E
KE
Andropolis
Department of Medicine, University of Illinois, Chicago, Ill.
Dipti V
DV
Panchal
Department of Medicine, University of Illinois, Chicago, Ill.
Zahraa
Z
Hajjiri
Division of Renal Diseases, Washington University School of Medicine, St. Louis, Mo.
Daniel C
DC
Brennan
Department of Medicine, University of Illinois, Chicago, Ill.
Patricia W
PW
Finn
Department of Medicine, University of Illinois, Chicago, Ill; Department of Surgery, University of Illinois, Chicago, Ill. Electronic address: perkinsd@uic.edu.
David L
DL
Perkins
D000328:Adult; D000368:Aged; D044822:Biodiversity; D016022:Case-Control Studies; D004352:Drug Resistance, Microbial; D064806:Dysbiosis / Q000382:microbiology* / Q000652:urine*; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000382:microbiology; D016030:Kidney Transplantation; D008297:Male; D053858:Metabolic Networks and Pathways; D064307:Microbiota; D008875:Middle Aged; D010802:Phylogeny; D025341:Principal Component Analysis; D014552:Urinary Tract Infections / Q000382:microbiology
D005492:Folic Acid
Annu Rev Pathol. 2012;7:99-122
21910623
Bioinformatics. 2014 Nov 1;30(21):3123-4
25061070
Nature. 2011 May 12;473(7346):174-80
21508958
Front Cell Infect Microbiol. 2013 Aug 15;3:41
23967406
Am J Transplant. 2014 Feb;14(2):416-27
24373208
Antimicrob Agents Chemother. 1995 Feb;39(2):279-89
7726483
J Clin Microbiol. 2014 Mar;52(3):871-6
24371246
PLoS One. 2012;7(5):e36298
22606251
Rev Infect Dis. 1982 Mar-Apr;4(2):261-9
7051228
Nat Rev Genet. 2012 Mar 13;13(4):260-70
22411464
Nature. 2011 Jun 15;474(7351):327-36
21677749
Gut. 2004 May;53(5):685-93
15082587
Clin Microbiol Infect. 2006 Feb;12(2):99-101
16441445
J Clin Microbiol. 2012 Apr;50(4):1376-83
22278835
Cell Host Microbe. 2014 Mar 12;15(3):374-81
24629343
Nat Rev Urol. 2015 Feb;12(2):81-90
25600098
PLoS One. 2015 Feb 11;10(2):e0117790
25671322
BMC Bioinformatics. 2008 Sep 19;9:386
18803844
Nucleic Acids Res. 2012 Jul;40(Web Server issue):W88-95
22645318
PLoS Biol. 2016 Aug 19;14(8):e1002533
27541692
Nat Biotechnol. 2014 Aug;32(8):834-41
24997786
Biochem Biophys Res Commun. 2016 Jan 22;469(4):967-77
26718401
Am Fam Physician. 1999 Mar 1;59(5):1225-34, 1237
10088877
J Bacteriol. 2012 Aug;194(16):4151-60
22661685
Nucleic Acids Res. 2014 Jan;42(Database issue):D199-205
24214961