Machine learning leveraging genomes from metagenomes identifies influential antibiotic resistance genes in the infant gut microbiome

mSystems

Volumn 3, Issue 1, 2018, Pages

  Rahman, Sumayah F ^a   Olm, Matthew R ^a   Morowitz, Michael J ^b   Banfield, Jillian F ^c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Antibiotic resistance; Clostridium difficile; Genome resolved metagenomics; Infant; Machine learning; Microbiome; Resistome

Indexed keywords

AMPICILLIN; BETA LACTAMASE; CEPHALOSPORIN; GENTAMICIN; PENICILLINASE; VANCOMYCIN;

AMINO ACID SEQUENCE; ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; ARTICLE; ARTIFICIAL MILK; BACTERIAL GENE; BACTERIAL SURVIVAL; BIRTH WEIGHT; CARBOHYDRATE TRANSPORT; CONTROLLED STUDY; FEMALE; GESTATIONAL AGE; HUMAN; INFANT; INTESTINE FLORA; MACHINE LEARNING; MAJOR CLINICAL STUDY; MALE; METAGENOME; METAGENOMICS; PEPTOCLOSTRIDIUM DIFFICILE; PREMATURITY; PRIORITY JOURNAL; RANDOM FOREST; VANCOMYCIN RESISTANCE;

EID: 85041537871     PISSN: None     EISSN: 23795077     Source Type: Journal    
DOI: 10.1128/mSystems.00123-17     Document Type: Article

References (70)

1. Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Project Group. 2005. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 365:579-587. https:// doi.org/10.1016/S0140-6736(05)17907-0.
2. Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, Scheld WM, Bartlett JG, Edwards J, Infectious Diseases Society of America. 2008. The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis 46:155-164. https://doi.org/10.1086/524891.
3. Penders J, Stobberingh EE, Savelkoul PHM, Wolffs PFG. 2013. The human microbiome as a reservoir of antimicrobial resistance. Front Microbiol 4:87. https://doi.org/10.3389/fmicb.2013.00087.
4. den Braak N, Van Belkum A, Van Keulen M, Vliegenthart J, Verbrugh HA, Endtz HP. 1998. Molecular characterization of vancomycinresistant enterococci from hospitalized patients and poultry products in the Netherlands. J Clin Microbiol 36:1927-1932.
5. Teuber M, Meile L, Schwarz F. 1999. Acquired antibiotic resistance in lactic acid bacteria from food. Antonie van Leeuwenhoek 76:115-137. https://doi.org/10.1023/A:1002035622988.
6. Simonsen GS, Lvseth A, Dahl KH, Kruse H. 1998. Transmission of VanAtype vancomycin-resistant enterococci and vanA resistance elements between chicken and humans at avoparcin-exposed farms. Microb Drug Resist 4:313-318. https://doi.org/10.1089/mdr.1998.4.313.
7. Langdon A, Crook N, Dantas G. 2016. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med 8:39. https://doi.org/10.1186/ s13073-016-0294-z.
8. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. 2006. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics 117:1979-1987. https://doi.org/10.1542/peds.2005-1707.
9. Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, Clemente JC, Knight R, Heath AC, Leibel RL, Rosenbaum M, Gordon JI. 2013. The long-term stability of the human gut microbiota. Science 341:1237439. https://doi.org/10.1126/science.1237439.
10. Greenwood C, Morrow AL, Lagomarcino AJ, Altaye M, Taft DH, Yu Z, Newburg DS, Ward DV, Schibler KR. 2014. Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J Pediatr 165:23-29. https://doi.org/ 10.1016/j.jpeds.2014.01.010.
11. Arboleya S, Sánchez B, Milani C, Duranti S, Solís G, Fernández N, de los Reyes-Gavilán CG, Ventura M, Margolles A, Gueimonde M. 2015. Intestinal microbiota development in preterm neonates and effect of perinatal antibiotics. J Pediatr 166:538-544. https://doi.org/10.1016/j.jpeds .2014.09.041.
12. Tanaka S, Kobayashi T, Songjinda P, Tateyama A, Tsubouchi M, Kiyohara C, Shirakawa T, Sonomoto K, Nakayama J. 2009. Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunol Med Microbiol 56:80-87. https://doi.org/10 .1111/j.1574-695X.2009.00553.x.
13. Jernberg C, Löfmark S, Edlund C, Jansson JK. 2007. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J 1:56-66. https://doi.org/10.1038/ismej.2007.3.
14. Gibson MK, Wang B, Ahmadi S, Burnham CA, Tarr PI, Warner BB, Dantas G. 2016. Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome. Nat Microbiol 1:16024. https://doi.org/10.1038/ nmicrobiol.2016.24.
15. Penders J, Vink C, Driessen C, London N, Thijs C, Stobberingh EE. 2005. Quantification of Bifidobacterium spp., Escherichia coli and Clostridium difficile in faecal samples of breast-fed and formula-fed infants by real-time PCR. FEMS Microbiol Lett 243:141-147. https://doi.org/10 .1016/j.femsle.2004.11.052.
16. Costello EK, Stagaman K, Dethlefsen L, Bohannan BJM, Relman DA. 2012. The application of ecological theory toward an understanding of the human microbiome. Science 336:1255-1262. https://doi.org/10.1126/ science.1224203.
17. Yassour M, Vatanen T, Siljander H, Hämäläinen AM, Härkönen T, Ryhänen SJ, Franzosa EA, Vlamakis H, Huttenhower C, Gevers D, Lander ES, Knip M; DIABIMMUNE Study Group, Xavier RJ. 2016. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med 8:343ra81. https://doi.org/ 10.1126/scitranslmed.aad0917.
18. Wampach L, Heintz-Buschart A, Hogan A, Muller EEL, Narayanasamy S, Laczny CC, Hugerth LW, Bindl L, Bottu J, Andersson AF, de Beaufort C, Wilmes P. 2017. Colonization and succession within the human gut microbiome by archaea, bacteria and microeukaryotes during the first year of life. Front Microbiol 8:738. https://doi.org/10.3389/fmicb.2017 .00738.
19. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, van den Brandt PA, Stobberingh EE. 2006. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 118:511-521. https:// doi.org/10.1542/peds.2005-2824.
20. Stewart CJ, Embleton ND, Clements E, Luna PN, Smith DP, Fofanova TY, Nelson A, Taylor G, Orr CH, Petrosino JF, Berrington JE, Cummings SP. 2017. Cesarean or vaginal birth does not impact the longitudinal development of the gut microbiome in a cohort of exclusively preterm infants. Front Microbiol 8:1-9. https://doi.org/10.3389/fmicb.2017.01008.
21. Chu DM, Ma J, Prince AL, Antony KM, Seferovic MD, Aagaard KM. 2017. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med 23:314-326. https://doi.org/10.1038/nm.4272.
22. Cong X, Xu W, Janton S, Henderson WA, Matson A, McGrath JM, Maas K, Graf J. 2016. Gut microbiome developmental patterns in early life of preterm infants: impacts of feeding and gender. PLoS One 11:e0152751. https://doi.org/10.1371/journal.pone.0152751.
23. Mshvildadze M, Neu J, Shuster J, Theriaque D, Li N, Mai V. 2010. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr 156:20-25. https://doi.org/10.1016/j.jpeds.2009.06 .063.
24. Keski-nisula L, Kyynäräinen HR, Kärkkäinen U, Karhukorpi J, Heinonen S, Pekkanen J. 2013. Maternal intrapartum antibiotics and decreased vertical transmission of Lactobacillus to neonates during birth. Acta Paediatr 102:480-485. https://doi.org/10.1111/apa.12186.
25. Fouhy F, Guinane CM, Hussey S, Wall R, Ryan CA, Dempsey EM, Murphy B, Ross RP, Fitzgerald GF, Stanton C, Cotter PD. 2012. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother 56:5811-5820. https://doi .org/10.1128/AAC.00789-12.
26. Glass HC, Andrew CT, Stayer SA, Brett C, Cladis F, Davis PJ. 2015. Outcomes for extremely premature infants. Anesth Analg 120:1337-1351. https://doi .org/10.1213/ANE.0000000000000705.
27. Underwood MA, Sohn K. 2017. The microbiota of the extremely preterm infant. Clin Perinatol 44:407-427. https://doi.org/10.1016/j.clp.2017.01 .005.
28. Schwiertz A, Gruhl B, Löbnitz M, Michel P, Radke M, Blaut M. 2003. Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants. Pediatr Res 54:393-399. https://doi.org/10.1203/01.PDR.0000078274.74607.7A.
29. Gibson MK, Forsberg KJ, Dantas G. 2015. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology. ISME J 9:207-216. https://doi.org/10.1038/ismej.2014.106.
30. Poole K. 2014. Stress responses as determinants of antimicrobial resistance in Pseudomonas aeruginosa: multidrug efflux and more. Can J Microbiol 60:783-791. https://doi.org/10.1139/cjm-2014-0666.
31. Poole K. 2008. Bacterial multidrug efflux pumps serve other functions. Microbe 3:179-185. https://doi.org/10.1128/microbe.3.179.1.
32. Nagayama K, Fujita K, Takashima Y, Ardin AC, Ooshima T, Matsumoto-Nakano M. 2014. Role of ABC transporter proteins in stress responses of Streptococcus mutans. Oral Heal Dent Manag 13:359-365.
33. Anderson MJ. 2001. A new method for non-parametric multivariate analysis of variance. Austral Ecol 26:32-46 https://doi.org/10.1111/j .1442-9993.2001.01070.pp.x
34. Anderson MJ, Walsh DCI. 2013. PERMANOVA, ANOSIM, and the Mantel test in the face of heterogeneous dispersions: what null hypothesis are you testing? Ecol Monogr 83:557-574. https://doi.org/10.1890/12-2010.1.
35. Szarecka A, Lesnock KR, Ramirez-Mondragon CA, Nicholas HB, Wymore T. 2011. The Class D beta-lactamase family: residues governing the maintenance and diversity of function. Protein Eng Des Sel 24:801-809. https://doi.org/10.1093/protein/gzr041.
36. Wang X, Quinn PJ. 2010. Lipopolysaccharide: biosynthetic pathway and structure modification. Prog Lipid Res 49:97-107. https://doi.org/10 .1016/j.plipres.2009.06.002.
37. Meredith TC, Aggarwal P, Mamat U, Lindner B, Woodard RW. 2006. Redefining the requisite lipopolysaccharide structure in Escherichia coli. ACS Chem Biol 1:33-42. https://doi.org/10.1021/cb0500015
38. Cech DL, Markin K, Woodard RW. 2017. Identification of a D-arabinose-5-phosphate isomerase in the Gram-positive Clostridium tetani. J Bacteriol 199. https://doi.org/10.1128/JB.00246-17.
39. Brown CT, Olm MR, Thomas BC, Banfield JF. 2016. Measurement of bacterial replication rates in microbial communities. Nat Biotechnol 34:1256-1263. https://doi.org/10.1038/nbt.3704.
40. Modi SR, Collins JJ, Relman DA. 2014. Antibiotics and the gut microbiota. J Clin Invest 124:4212-4218. https://doi.org/10.1172/JCI72333.
41. Piddock LJV. 2006. Multidrug-resistance efflux pumps - not just for resistance. Nat Rev Microbiol 4:629-636. https://doi.org/10.1038/nrmicro 1464.
42. Kanehisa M, Goto S. 2000. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27-30. https://doi.org/10.1093/nar/28 .1.27.
43. Hastie T, Rosset S, Zhu J, Zou H. 2009. Multi-class AdaBoost. Stat Interface 2:349-360. https://doi.org/10.4310/SII.2009.v2.n3.a8.
44. Hernandez Valladares MH, Felici A, Weber G, Adolph HW, Zeppezauer M, Rossolini GM, Amicosante G, Frère JM, Galleni M. 1997. Zn(II) dependence of the Aeromonas hydrophila AE036 metallo-beta-lactamase activity and stability. Biochemistry 36:11534-11541. https://doi.org/10 .1021/bi971056h.
45. Hansen LH, Jensen LB, Sørensen HI, Sørensen SJ. 2007. Substrate specificity of the OqxAB multidrug resistance pump in Escherichia coli and selected enteric bacteria. J Antimicrob Chemother 60:145-147. https:// doi.org/10.1093/jac/dkm167.
46. Jacoby GA, Medeiros AA. 1991. More extended-spectrum betalactamases. Antimicrob Agents Chemother 35:1697-1704. https://doi .org/10.1128/AAC.35.9.1697.
47. Hughes D. 2003. Exploiting genomics, genetics and chemistry to combat antibiotic resistance. Nat Rev Genet 4:432-441. https://doi.org/10.1038/ nrg1084.
48. Boyce JM. 1997. Vancomycin-resistant enterococcus. Detection, epidemiology and control measures. Infect Dis Clin North Am 11:367-384. https://doi.org/10.1016/S0891-5520(05)70361-5.
49. Périchon B, Courvalin P. 2009. VanA-type vancomycin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 53:4580-4587. https:// doi.org/10.1128/AAC.00346-09.
50. Arthur M, Quintiliani R. 2001. Regulation of VanA-and VanB-type glycopeptide resistance in enterococci. Antimicrob Agents Chemother 45: 375-381. https://doi.org/10.1128/AAC.45.2.375-381.2001.
51. Li XZ, Nikaido H. 2009. Efflux-mediated drug resistance in bacteria: an update. Drugs 69:1555-1623. https://doi.org/10.2165/11317030-000000000-00000.
52. DiGiulio DB, Callahan BJ, McMurdie PJ, Costello EK, Lyell DJ, Robaczewska A, Sun CL, Goltsman DSA, Wong RJ, Shaw G, Stevenson DK, Holmes SP, Relman DA. 2015. Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci U S A 112: 11060-11065. https://doi.org/10.1073/pnas.1502875112.
53. Yazdani M, Taylor BC, Debelius JW, Li W, Knight R, Smarr L. 2016. Using machine learning to identify major shifts in human gut microbiome protein family abundance in disease, p 1273-1280. In IEEE International Conference on Big Data, Washington, DC.
54. Kumar V, Sun P, Vamathevan J, Li Y, Ingraham K, Palmer L, Huang J, Brown JR. 2011. Comparative genomics of Klebsiella pneumoniae strains with different antibiotic resistance profiles. Antimicrob Agents Chemother 55:4267-4276. https://doi.org/10.1128/AAC.00052-11.
55. Raveh-Sadka T, Thomas BC, Singh A, Firek B, Brooks B, Castelle CJ, Sharon I, Baker R, Good M, Morowitz MJ, Banfield JF. 2015. Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development. Elife 4:e05477. https://doi.org/10 .7554/eLife.05477.
56. Raveh-Sadka T, Firek B, Sharon I, Baker R, Brown CT, Thomas BC, Morowitz MJ, Banfield JF. 2016. Evidence for persistent and shared bacterial strains against a background of largely unique gut colonization in hospitalized premature infants. ISME J 10:2817-2830. https://doi.org/10 .1038/ismej.2016.83.
57. Brooks B, Olm MR, Firek BA, Baker R, Thomas BC, Morowitz MJ, Banfield JF. 27 November 2017. Strain-resolved analysis of the hospital room and hospitalized infants reveals overlap between the human and room microbiome. Nat Commun https://doi.org/10.1038/s41467-017-02018-w.
58. Langmead B, Salzberg SL. 2012. Fast gapped-read alignment with Bowtie 2. Nat Methods 9:357-359. https://doi.org/10.1038/nmeth.1923.
59. Peng Y, Leung HCM, Yiu SM, Chin FYL. 2012. IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth. Bioinformatics 28:1420-1428. https://doi.org/10.1093/ bioinformatics/bts174.
60. Hyatt D, Chen GL, Locascio PF, Land ML, Larimer FW, Hauser LJ. 2010. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics 11:119. https://doi.org/10.1186/1471-2105-11-119.
61. Zaharia M, Bolosky WJ, Curtis K, Fox A, Patterson D, Shenker S, Stoica I, Karp RM, Sittler T. 2011. Faster and more accurate sequence alignment with SNAP. arXiv https://arxiv.org/abs/1111.5572.
62. Alneberg J, Bjarnason BS, De Bruijn I, Schirmer M, Quick J, Ijaz UZ, Lahti L, Loman NJ, Andersson AF, Quince C. 2014. Binning metagenomic contigs by coverage and composition. Nat Methods 11:1144-1146. https://doi.org/10.1038/nmeth.3103.
63. Olm MR, Brown CT, Brooks B, Banfield JF. 2017. dRep: a tool for fast and accurate genome de-replication that enables tracking of microbial genotypes and improved genome recovery from metagenomes. ISME J 11:2864-2868. https://doi.org/10.1038/ismej.2017.126.
64. Laing C, Buchanan C, Taboada EN, Zhang Y, Kropinski A, Villegas A, Thomas JE, Gannon VPJ. 2010. Pan-genome sequence analysis using Panseq: an online tool for the rapid analysis of core and accessory genomic regions. BMC Bioinformatics 11:461. https://doi.org/10.1186/ 1471-2105-11-461.
65. Finn RD, Clements J, Eddy SR. 2011. HMMER web server: interactive sequence similarity searching. Nucleic Acids Res 39:W29-W37. https:// doi.org/10.1093/nar/gkr367.
66. McArdle BH, Anderson MJ. 2001. Fitting multivariate models to community data: a comment on distance-based redundancy analysis. Ecology 82: 290-297. https://doi.org/10.1890/0012-9658(2001)082[0290:FMMTCD]2 .0.CO;2.
67. Dixon P. 2003. VEGAN, a package of R functions for community ecology. J Veg Sci 14:927-930. https://doi.org/10.1111/j.1654-1103.2003 .tb02228.x.
68. Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, Blondel M, Prettenhofer P, Weiss R, Dubourg V, Vanderplas J, Passos A, Cournapeau D, Brucher M, Perrot M, Duchesnay E. 2012. Scikit-learn: machine learning in Python. J Mach Learn Res 12:2825-2830. http:// www.jmlr.org/papers/v12/pedregosa11a.html.
69. Edgar RC. 2004. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792-1797. https://doi .org/10.1093/nar/gkh340.
70. Stamatakis A. 2014. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30:1312-1313. https://doi.org/10.1093/bioinformatics/btu033.