Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome

Peters, Samantha L.; Morowitz, Michael J.; Hettich, Robert L.

doi:10.3389/fmicb.2022.958638

Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome

Journal Article · Sun Nov 20 23:00:00 EST 2022 · Frontiers in Microbiology

DOI:https://doi.org/10.3389/fmicb.2022.958638· OSTI ID:1908085

Peters, Samantha L. ^[1]; Morowitz, Michael J. ^[2]; ^[3]

Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division; Univ. of Tennessee, Knoxville, TN (United States)
Univ. of Pittsburgh, PA (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division

The human gut microbiome, which develops and stabilizes during the early stages of infant life, plays an essential role in host health through the production of metabolic resources and the stimulation and training of the immune system. To study colonization and community functional dynamics of the microbiota based on responses to host immune processes during the normal and dysbiotic establishment of the gut, metaproteomics was conducted on 91 fecal samples collected over the first 90 days of life from 17 hospitalized premature infants. Microbial responses to antibiotic administration and host-imposed metal bactericidal control correlated with community assembly and resiliency of microbes in the developing preterm gut. Specifically, proteins related to antibiotic resistance and metal homeostasis mechanisms were predominant in persisting members in the infant gut environment over the first several weeks of life. Overall, this metaproteomics study provides a unique approach to examine the temporal expansion and resilience of microbial colonization, as it allows simultaneous examination of both host and microbial metabolic activities. Understanding the interplay between host and microbes may elucidate the microbiome’s potential immunomodulatory roles relevant to necrotizing enterocolitis and other dysbiotic conditions in preterm infants.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1908085

Journal Information:: Frontiers in Microbiology, Journal Name: Frontiers in Microbiology Journal Issue: 1 Vol. 13; ISSN 1664-302X

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

References (65)

MS Amanda 2.0: Advancements in the standalone implementation Dorfer, Viktoria; Strobl, Marina; Winkler, Stephan Rapid Communications in Mass Spectrometry, Vol. 35, Issue 11 https://doi.org/10.1002/rcm.9088	journal	May 2021
Trace metals and animal health: Interplay of the gut microbiota with iron, manganese, zinc, and copper Pajarillo, Edward Alain B.; Lee, Eunsook; Kang, Dae-Kyung Animal Nutrition, Vol. 7, Issue 3 https://doi.org/10.1016/j.aninu.2021.03.005	journal	September 2021
Bacterial manganese sensing and homeostasis Waters, Lauren S. Current Opinion in Chemical Biology, Vol. 55 https://doi.org/10.1016/j.cbpa.2020.01.003	journal	April 2020
Nutrient Metal Sequestration by Calprotectin Inhibits Bacterial Superoxide Defense, Enhancing Neutrophil Killing of Staphylococcus aureus Kehl-Fie, Thomas E.; Chitayat, Seth; Hood, M. Indriati Cell Host & Microbe, Vol. 10, Issue 2 https://doi.org/10.1016/j.chom.2011.07.004	journal	August 2011
Zinc Sequestration by the Neutrophil Protein Calprotectin Enhances Salmonella Growth in the Inflamed Gut Liu, Janet Z.; Jellbauer, Stefan; Poe, Adam J. Cell Host & Microbe, Vol. 11, Issue 3 https://doi.org/10.1016/j.chom.2012.01.017	journal	March 2012
Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration Diaz-Ochoa, Vladimir E.; Lam, Diana; Lee, Carlin S. Cell Host & Microbe, Vol. 19, Issue 6 https://doi.org/10.1016/j.chom.2016.05.005	journal	June 2016
Impact of Toll-Like Receptor 4 Signaling in Necrotizing Enterocolitis Mihi, Belgacem; Good, Misty Clinics in Perinatology, Vol. 46, Issue 1 https://doi.org/10.1016/j.clp.2018.09.007	journal	March 2019
Metal tolerance in emerging clinically relevant multidrug-resistant Salmonella enterica serotype 4,[5],12:i:− clones circulating in Europe Mourão, Joana; Novais, Carla; Machado, Jorge International Journal of Antimicrobial Agents, Vol. 45, Issue 6 https://doi.org/10.1016/j.ijantimicag.2015.01.013	journal	June 2015
Extended-spectrum β-lactamase characterisation and heavy metal resistance of Enterobacteriaceae strains isolated from hospital environmental surfaces Touati, A.; Zenati, K.; Brasme, L. Journal of Hospital Infection, Vol. 75, Issue 1 https://doi.org/10.1016/j.jhin.2010.01.001	journal	May 2010
Selection of resistance by antimicrobial coatings in the healthcare setting Pietsch, F.; O'Neill, A. J.; Ivask, A. Journal of Hospital Infection, Vol. 106, Issue 1 https://doi.org/10.1016/j.jhin.2020.06.006	journal	September 2020
Iron at the host-microbe interface Gerner, Romana R.; Nuccio, Sean-Paul; Raffatellu, Manuela Molecular Aspects of Medicine, Vol. 75 https://doi.org/10.1016/j.mam.2020.100895	journal	October 2020
Parsing the functional specificity of Siderocalin/Lipocalin 2/NGAL for siderophores and related small-molecule ligands Clifton, Matthew C.; Rupert, Peter B.; Hoette, Trisha M. Journal of Structural Biology: X, Vol. 2 https://doi.org/10.1016/j.yjsbx.2019.100008	journal	April 2019
High frequencies of antibiotic resistance genes in infants’ meconium and early fecal samples Gosalbes, M. J.; Vallès, Y.; Jiménez-Hernández, N. Journal of Developmental Origins of Health and Disease, Vol. 7, Issue 1 https://doi.org/10.1017/S2040174415001506	journal	September 2015
CharmeRT: Boosting Peptide Identifications by Chimeric Spectra Identification and Retention Time Prediction Dorfer, Viktoria; Maltsev, Sergey; Winkler, Stephan Journal of Proteome Research, Vol. 17, Issue 8 https://doi.org/10.1021/acs.jproteome.7b00836	journal	June 2018
Copper Transport and Trafficking at the Host–Bacterial Pathogen Interface Fu, Yue; Chang, Feng-Ming James; Giedroc, David P. Accounts of Chemical Research, Vol. 47, Issue 12 https://doi.org/10.1021/ar500300n	journal	October 2014
Antimicrobial Action of Copper Is Amplified via Inhibition of Heme Biosynthesis Djoko, Karrera Y.; McEwan, Alastair G. ACS Chemical Biology, Vol. 8, Issue 10 https://doi.org/10.1021/cb4002443	journal	August 2013
Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut Xiong, Weili; Giannone, Richard J.; Morowitz, Michael J. Journal of Proteome Research, Vol. 14, Issue 1 https://doi.org/10.1021/pr500936p	journal	October 2014
Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome Gibson, Molly K.; Wang, Bin; Ahmadi, Sara Nature Microbiology, Vol. 1, Issue 4 https://doi.org/10.1038/nmicrobiol.2016.24	journal	March 2016
Ménage à trois in the human gut: interactions between host, bacteria and phages Mirzaei, Mohammadali Khan; Maurice, Corinne F. Nature Reviews Microbiology, Vol. 15, Issue 7 https://doi.org/10.1038/nrmicro.2017.30	journal	May 2017
Antimicrobial activity of metals: mechanisms, molecular targets and applications Lemire, Joseph A.; Harrison, Joe J.; Turner, Raymond J. Nature Reviews Microbiology, Vol. 11, Issue 6 https://doi.org/10.1038/nrmicro3028	journal	May 2013
Enteric dysbiosis and fecal calprotectin expression in premature infants Ho, Thao T. B.; Groer, Maureen W.; Kane, Bradley Pediatric Research, Vol. 85, Issue 3 https://doi.org/10.1038/s41390-018-0254-y	journal	December 2018
Human breast milk exosomes may protect against necrotizing enterocolitis in preterm infants Madden, Jessica W. Pediatric Research, Vol. 90, Issue 2 https://doi.org/10.1038/s41390-021-01580-w	journal	May 2021
Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome Gasparrini, Andrew J.; Wang, Bin; Sun, Xiaoqing Nature Microbiology, Vol. 4, Issue 12 https://doi.org/10.1038/s41564-019-0550-2	journal	September 2019
Clinical implications of preterm infant gut microbiome development Healy, David B.; Ryan, C. Anthony; Ross, R. Paul Nature Microbiology, Vol. 7, Issue 1 https://doi.org/10.1038/s41564-021-01025-4	journal	December 2021
Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants Gopalakrishna, Kathyayini P.; Macadangdang, Benjamin R.; Rogers, Matthew B. Nature Medicine, Vol. 25, Issue 7 https://doi.org/10.1038/s41591-019-0480-9	journal	June 2019
Maturation of the preterm gastrointestinal tract can be defined by host and microbial markers for digestion and barrier defense Henderickx, Jannie G. E.; Zwittink, Romy D.; Renes, Ingrid B. Scientific Reports, Vol. 11, Issue 1 https://doi.org/10.1038/s41598-021-92222-y	journal	June 2021
Persistence of birth mode-dependent effects on gut microbiome composition, immune system stimulation and antimicrobial resistance during the first year of life Busi, Susheel Bhanu; de Nies, Laura; Habier, Janine ISME Communications, Vol. 1, Issue 1 https://doi.org/10.1038/s43705-021-00003-5	journal	March 2021
Necrotizing enterocolitis: Pathophysiology from a historical context Hackam, David; Caplan, Michael Seminars in Pediatric Surgery, Vol. 27, Issue 1 https://doi.org/10.1053/j.sempedsurg.2017.11.003	journal	February 2018
The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity Macomber, L.; Imlay, J. A. Proceedings of the National Academy of Sciences, Vol. 106, Issue 20 https://doi.org/10.1073/pnas.0812808106	journal	May 2009
Antibiotic treatment affects the expression levels of copper transporters and the isotopic composition of copper in the colon of mice Miller, Kerri A.; Vicentini, Fernando A.; Hirota, Simon A. Proceedings of the National Academy of Sciences, Vol. 116, Issue 13 https://doi.org/10.1073/pnas.1814047116	journal	March 2019
A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity White, Carine; Lee, Jaekwon; Kambe, Taiho Journal of Biological Chemistry, Vol. 284, Issue 49 https://doi.org/10.1074/jbc.M109.070201	journal	October 2009
A Single PDZ Domain Protein Interacts with the Menkes Copper ATPase, ATP7A Stephenson, Sarah E. M.; Dubach, Daphne; Lim, Chris M. Journal of Biological Chemistry, Vol. 280, Issue 39 https://doi.org/10.1074/jbc.M505889200	journal	September 2005
Microbial Copper-binding Siderophores at the Host-Pathogen Interface Koh, Eun-Ik; Henderson, Jeffrey P. Journal of Biological Chemistry, Vol. 290, Issue 31 https://doi.org/10.1074/jbc.R115.644328	journal	July 2015
The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens Djoko, Karrera Y.; Ong, Cheryl-lynn Y.; Walker, Mark J. Journal of Biological Chemistry, Vol. 290, Issue 31 https://doi.org/10.1074/jbc.R115.647099	journal	June 2015
PLEKHA5, PLEKHA6, and PLEKHA7 bind to PDZD11 to target the Menkes ATPase ATP7A to the cell periphery and regulate copper homeostasis Sluysmans, Sophie; Méan, Isabelle; Xiao, Tong Molecular Biology of the Cell, Vol. 32, Issue 21 https://doi.org/10.1091/mbc.E21-07-0355	journal	November 2021
Search and clustering orders of magnitude faster than BLAST Edgar, Robert C. Bioinformatics, Vol. 26, Issue 19, p. 2460-2461 https://doi.org/10.1093/bioinformatics/btq461	journal	August 2010
A genome-wide screen reveals the involvement of enterobactin-mediated iron acquisition inEscherichia colisurvival during copper stress Casanova-Hampton, Kaitlin; Carey, Alexis; Kassam, Sarah Metallomics, Vol. 13, Issue 9 https://doi.org/10.1093/mtomcs/mfab052	journal	August 2021
eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses Huerta-Cepas, Jaime; Szklarczyk, Damian; Heller, Davide Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky1085	journal	November 2018
CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database Alcock, Brian P.; Raphenya, Amogelang R.; Lau, Tammy T. Y. Nucleic Acids Research https://doi.org/10.1093/nar/gkz935	journal	October 2019
NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism Kim, Youngchang; Cunningham, Mark A.; Mire, Joseph The FASEB Journal, Vol. 27, Issue 5 https://doi.org/10.1096/fj.12-224014	journal	May 2013
Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors Chen, Yuhao; Brook, Thomas C.; Soe, Cho Zin Microbial Genomics, Vol. 6, Issue 6 https://doi.org/10.1099/mgen.0.000377	journal	June 2020
Metal limitation and toxicity at the interface between host and pathogen Becker, Kyle W.; Skaar, Eric P. FEMS Microbiology Reviews, Vol. 38, Issue 6 https://doi.org/10.1111/1574-6976.12087	journal	November 2014
A review of the innate immune defence of the human foetus and newborn, with the emphasis on antimicrobial peptides Kai-Larsen, Ylva; Gudmundsson, Gudmundur H.; Agerberth, Birgitta Acta Paediatrica, Vol. 103, Issue 10 https://doi.org/10.1111/apa.12700	journal	June 2014
The copper regulon of the human fungal pathogen Cryptococcus neoformans H99 Ding, Chen; Yin, Jun; Tovar, Edgar Mauricio Medina Molecular Microbiology, Vol. 81, Issue 6 https://doi.org/10.1111/j.1365-2958.2011.07794.x	journal	August 2011
Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function Olszak, Torsten; An, Dingding; Zeissig, Sebastian Science, Vol. 336, Issue 6080 https://doi.org/10.1126/science.1219328	journal	April 2012
How colonization by microbiota in early life shapes the immune system Gensollen, Thomas; Iyer, Shankar S.; Kasper, Dennis L. Science, Vol. 352, Issue 6285 https://doi.org/10.1126/science.aad9378	journal	April 2016
Novel erm (T)-Carrying Multiresistance Plasmids from Porcine and Human Isolates of Methicillin-Resistant Staphylococcus aureus ST398 That Also Harbor Cadmium and Copper Resistance Determinants Gómez-Sanz, Elena; Kadlec, Kristina; Feßler, Andrea T. Antimicrobial Agents and Chemotherapy, Vol. 57, Issue 7 https://doi.org/10.1128/AAC.00171-13	journal	July 2013
High-Throughput Sequencing Reveals the Incomplete, Short-Term Recovery of Infant Gut Microbiota following Parenteral Antibiotic Treatment with Ampicillin and Gentamicin Fouhy, Fiona; Guinane, Caitriona M.; Hussey, Seamus Antimicrobial Agents and Chemotherapy, Vol. 56, Issue 11 https://doi.org/10.1128/AAC.00789-12	journal	September 2012
Heavy Metal Resistance Genes Are Associated with bla _NDM-1 - and bla _CTX-M-15 -Carrying Enterobacteriaceae Yang, Qiu E.; Agouri, Siham Rajab; Tyrrell, Jonathan Mark Antimicrobial Agents and Chemotherapy, Vol. 62, Issue 5 https://doi.org/10.1128/AAC.02642-17	journal	May 2018
tcrB, a Gene Conferring Transferable Copper Resistance in Enterococcus faecium: Occurrence, Transferability, and Linkage to Macrolide and Glycopeptide Resistance Hasman, Henrik; Aarestrup, Frank M. Antimicrobial Agents and Chemotherapy, Vol. 46, Issue 5 https://doi.org/10.1128/AAC.46.5.1410-1416.2002	journal	May 2002
Copper Resistance in Enterococcus faecium , Mediated by the tcrB Gene, Is Selected by Supplementation of Pig Feed with Copper Sulfate Hasman, Henrik; Kempf, Isabelle; Chidaine, Bérangère Applied and Environmental Microbiology, Vol. 72, Issue 9 https://doi.org/10.1128/AEM.02979-05	journal	September 2006
MntABC and MntH Contribute to Systemic Staphylococcus aureus Infection by Competing with Calprotectin for Nutrient Manganese Kehl-Fie, Thomas E.; Zhang, Yaofang; Moore, Jessica L. Infection and Immunity, Vol. 81, Issue 9 https://doi.org/10.1128/IAI.00420-13	journal	July 2013
Linkage between Catecholate Siderophores and the Multicopper Oxidase CueO in Escherichia coli Grass, G.; Thakali, K.; Klebba, P. E. Journal of Bacteriology, Vol. 186, Issue 17 https://doi.org/10.1128/JB.186.17.5826-5833.2004	journal	August 2004
Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles Brown, Christopher T.; Xiong, Weili; Olm, Matthew R. mBio, Vol. 9, Issue 2 https://doi.org/10.1128/mBio.00441-18	journal	April 2018
Selection and dissemination of antimicrobial resistance in Agri-food production Cheng, Guyue; Ning, Jianan; Ahmed, Saeed Antimicrobial Resistance & Infection Control, Vol. 8, Issue 1 https://doi.org/10.1186/s13756-019-0623-2	journal	October 2019
Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life Xiong, Weili; Brown, Christopher T.; Morowitz, Michael J. Microbiome, Vol. 5, Issue 1 https://doi.org/10.1186/s40168-017-0290-6	journal	July 2017
Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates Nogacka, Alicja; Salazar, Nuria; Suárez, Marta Microbiome, Vol. 5, Issue 1 https://doi.org/10.1186/s40168-017-0313-3	journal	August 2017
Patterns of Early Gut Colonization Shape Future Immune Responses of the Host Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris; Kverka, Miloslav PLoS ONE, Vol. 7, Issue 3 https://doi.org/10.1371/journal.pone.0034043	journal	March 2012
Copper at the Front Line of the Host-Pathogen Battle Festa, Richard A.; Thiele, Dennis J. PLoS Pathogens, Vol. 8, Issue 9 https://doi.org/10.1371/journal.ppat.1002887	journal	September 2012
Mechanisms of Microbe–Host Interaction in Crohn’s Disease: Dysbiosis vs. Pathobiont Selection Buttó, Ludovica F.; Schaubeck, Monika; Haller, Dirk Frontiers in Immunology, Vol. 6 https://doi.org/10.3389/fimmu.2015.00555	journal	November 2015
The immune consequences of preterm birth Melville, Jacqueline M.; Moss, Timothy J. M. Frontiers in Neuroscience, Vol. 7 https://doi.org/10.3389/fnins.2013.00079	journal	January 2013
Cu Homeostasis in Bacteria: The Ins and Outs Andrei, Andreea; Öztürk, Yavuz; Khalfaoui-Hassani, Bahia Membranes, Vol. 10, Issue 9 https://doi.org/10.3390/membranes10090242	journal	September 2020
The composition of the gut microbiota throughout life, with an emphasis on early life Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine Microbial Ecology in Health & Disease, Vol. 26, Issue 0 https://doi.org/10.3402/mehd.v26.26050	journal	February 2015
Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life [Supplementary Data] Xiong, Weili; Brown, Christopher; Morowitz, Michael Figshare-Supplementary information for journal article at DOI: 10.1186/s40168-017-0290-6, 9 files https://doi.org/10.6084/m9.figshare.c.3823267	dataset	July 2017
Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates Nogacka, Alicja; Salazar, Nuria; Suárez, Marta Figshare https://doi.org/10.6084/m9.figshare.c.3846829	collection	January 2017

Similar Records

Development of the preterm infant gut microbiome: A research priority

Journal Article · Mon Oct 13 00:00:00 EDT 2014 · Microbiome · OSTI ID:1225363

Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life

Journal Article · Mon Jul 10 00:00:00 EDT 2017 · Microbiome · OSTI ID:1407990

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
antibiotic resistance
host immune system
human infant faecal microbiota
human microbiome
metal bactericidal control
metaproteomics

Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome

Citation Formats

References (65)

Similar Records

Related Subjects