Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome
Abstract
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.
- Authors:
-
[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
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH)
- OSTI Identifier:
- 1908085
- Grant/Contract Number:
- AC05-00OR22725; R01GM103600
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Frontiers in Microbiology
- Additional Journal Information:
- Journal Volume: 13; Journal Issue: 1; Journal ID: ISSN 1664-302X
- Publisher:
- Frontiers Research Foundation
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; human microbiome; human infant faecal microbiota; metaproteomics; host immune system; metal bactericidal control; antibiotic resistance
Citation Formats
Peters, Samantha L., Morowitz, Michael J., and Hettich, Robert L. Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome. United States: N. p., 2022.
Web. doi:10.3389/fmicb.2022.958638.
Peters, Samantha L., Morowitz, Michael J., & Hettich, Robert L. Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome. United States. https://doi.org/10.3389/fmicb.2022.958638
Peters, Samantha L., Morowitz, Michael J., and Hettich, Robert L. Mon .
"Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome". United States. https://doi.org/10.3389/fmicb.2022.958638. https://www.osti.gov/servlets/purl/1908085.
@article{osti_1908085,
title = {Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome},
author = {Peters, Samantha L. and Morowitz, Michael J. and Hettich, Robert L.},
abstractNote = {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.},
doi = {10.3389/fmicb.2022.958638},
journal = {Frontiers in Microbiology},
number = 1,
volume = 13,
place = {United States},
year = {Mon Nov 21 00:00:00 EST 2022},
month = {Mon Nov 21 00:00:00 EST 2022}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Patterns of Early Gut Colonization Shape Future Immune Responses of the Host
journal, March 2012
- Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris; Kverka, Miloslav
- PLoS ONE, Vol. 7, Issue 3
Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration
journal, June 2016
- Diaz-Ochoa, Vladimir E.; Lam, Diana; Lee, Carlin S.
- Cell Host & Microbe, Vol. 19, Issue 6
Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function
journal, April 2012
- Olszak, Torsten; An, Dingding; Zeissig, Sebastian
- Science, Vol. 336, Issue 6080
Human breast milk exosomes may protect against necrotizing enterocolitis in preterm infants
journal, May 2021
- Madden, Jessica W.
- Pediatric Research, Vol. 90, Issue 2
How colonization by microbiota in early life shapes the immune system
journal, April 2016
- Gensollen, Thomas; Iyer, Shankar S.; Kasper, Dennis L.
- Science, Vol. 352, Issue 6285
MntABC and MntH Contribute to Systemic Staphylococcus aureus Infection by Competing with Calprotectin for Nutrient Manganese
journal, July 2013
- Kehl-Fie, Thomas E.; Zhang, Yaofang; Moore, Jessica L.
- Infection and Immunity, Vol. 81, Issue 9
Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome
journal, September 2019
- Gasparrini, Andrew J.; Wang, Bin; Sun, Xiaoqing
- Nature Microbiology, Vol. 4, Issue 12
Nutrient Metal Sequestration by Calprotectin Inhibits Bacterial Superoxide Defense, Enhancing Neutrophil Killing of Staphylococcus aureus
journal, August 2011
- Kehl-Fie, Thomas E.; Chitayat, Seth; Hood, M. Indriati
- Cell Host & Microbe, Vol. 10, Issue 2
Linkage between Catecholate Siderophores and the Multicopper Oxidase CueO in Escherichia coli
journal, August 2004
- Grass, G.; Thakali, K.; Klebba, P. E.
- Journal of Bacteriology, Vol. 186, Issue 17
Mechanisms of Microbe–Host Interaction in Crohn’s Disease: Dysbiosis vs. Pathobiont Selection
journal, November 2015
- Buttó, Ludovica F.; Schaubeck, Monika; Haller, Dirk
- Frontiers in Immunology, Vol. 6
Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome
journal, March 2016
- Gibson, Molly K.; Wang, Bin; Ahmadi, Sara
- Nature Microbiology, Vol. 1, Issue 4
Bacterial manganese sensing and homeostasis
journal, April 2020
- Waters, Lauren S.
- Current Opinion in Chemical Biology, Vol. 55
Zinc Sequestration by the Neutrophil Protein Calprotectin Enhances Salmonella Growth in the Inflamed Gut
journal, March 2012
- Liu, Janet Z.; Jellbauer, Stefan; Poe, Adam J.
- Cell Host & Microbe, Vol. 11, Issue 3
Antibiotic treatment affects the expression levels of copper transporters and the isotopic composition of copper in the colon of mice
journal, March 2019
- Miller, Kerri A.; Vicentini, Fernando A.; Hirota, Simon A.
- Proceedings of the National Academy of Sciences, Vol. 116, Issue 13
Cu Homeostasis in Bacteria: The Ins and Outs
journal, September 2020
- Andrei, Andreea; Öztürk, Yavuz; Khalfaoui-Hassani, Bahia
- Membranes, Vol. 10, Issue 9
A review of the innate immune defence of the human foetus and newborn, with the emphasis on antimicrobial peptides
journal, June 2014
- Kai-Larsen, Ylva; Gudmundsson, Gudmundur H.; Agerberth, Birgitta
- Acta Paediatrica, Vol. 103, Issue 10
Metal limitation and toxicity at the interface between host and pathogen
journal, November 2014
- Becker, Kyle W.; Skaar, Eric P.
- FEMS Microbiology Reviews, Vol. 38, Issue 6
Copper at the Front Line of the Host-Pathogen Battle
journal, September 2012
- Festa, Richard A.; Thiele, Dennis J.
- PLoS Pathogens, Vol. 8, Issue 9
Necrotizing enterocolitis: Pathophysiology from a historical context
journal, February 2018
- Hackam, David; Caplan, Michael
- Seminars in Pediatric Surgery, Vol. 27, Issue 1
NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism
journal, May 2013
- Kim, Youngchang; Cunningham, Mark A.; Mire, Joseph
- The FASEB Journal, Vol. 27, Issue 5
Impact of Toll-Like Receptor 4 Signaling in Necrotizing Enterocolitis
journal, March 2019
- Mihi, Belgacem; Good, Misty
- Clinics in Perinatology, Vol. 46, Issue 1
Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates
journal, August 2017
- Nogacka, Alicja; Salazar, Nuria; Suárez, Marta
- Microbiome, Vol. 5, Issue 1
CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database
journal, October 2019
- Alcock, Brian P.; Raphenya, Amogelang R.; Lau, Tammy T. Y.
- Nucleic Acids Research
Iron at the host-microbe interface
journal, October 2020
- Gerner, Romana R.; Nuccio, Sean-Paul; Raffatellu, Manuela
- Molecular Aspects of Medicine, Vol. 75
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
journal, July 2013
- Gómez-Sanz, Elena; Kadlec, Kristina; Feßler, Andrea T.
- Antimicrobial Agents and Chemotherapy, Vol. 57, Issue 7
Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut
journal, October 2014
- Xiong, Weili; Giannone, Richard J.; Morowitz, Michael J.
- Journal of Proteome Research, Vol. 14, Issue 1
A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity
journal, October 2009
- White, Carine; Lee, Jaekwon; Kambe, Taiho
- Journal of Biological Chemistry, Vol. 284, Issue 49
Antimicrobial Action of Copper Is Amplified via Inhibition of Heme Biosynthesis
journal, August 2013
- Djoko, Karrera Y.; McEwan, Alastair G.
- ACS Chemical Biology, Vol. 8, Issue 10
High-Throughput Sequencing Reveals the Incomplete, Short-Term Recovery of Infant Gut Microbiota following Parenteral Antibiotic Treatment with Ampicillin and Gentamicin
journal, September 2012
- Fouhy, Fiona; Guinane, Caitriona M.; Hussey, Seamus
- Antimicrobial Agents and Chemotherapy, Vol. 56, Issue 11
Trace metals and animal health: Interplay of the gut microbiota with iron, manganese, zinc, and copper
journal, September 2021
- Pajarillo, Edward Alain B.; Lee, Eunsook; Kang, Dae-Kyung
- Animal Nutrition, Vol. 7, Issue 3
Search and clustering orders of magnitude faster than BLAST
journal, August 2010
- Edgar, Robert C.
- Bioinformatics, Vol. 26, Issue 19, p. 2460-2461
The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens
journal, June 2015
- Djoko, Karrera Y.; Ong, Cheryl-lynn Y.; Walker, Mark J.
- Journal of Biological Chemistry, Vol. 290, Issue 31
MS Amanda 2.0: Advancements in the standalone implementation
journal, May 2021
- Dorfer, Viktoria; Strobl, Marina; Winkler, Stephan
- Rapid Communications in Mass Spectrometry, Vol. 35, Issue 11
Copper Resistance in
Enterococcus faecium
, Mediated by the
tcrB
Gene, Is Selected by Supplementation of Pig Feed with Copper Sulfate
journal, September 2006
- Hasman, Henrik; Kempf, Isabelle; Chidaine, Bérangère
- Applied and Environmental Microbiology, Vol. 72, Issue 9
Metal tolerance in emerging clinically relevant multidrug-resistant Salmonella enterica serotype 4,[5],12:i:− clones circulating in Europe
journal, June 2015
- Mourão, Joana; Novais, Carla; Machado, Jorge
- International Journal of Antimicrobial Agents, Vol. 45, Issue 6
Persistence of birth mode-dependent effects on gut microbiome composition, immune system stimulation and antimicrobial resistance during the first year of life
journal, March 2021
- Busi, Susheel Bhanu; de Nies, Laura; Habier, Janine
- ISME Communications, Vol. 1, Issue 1
PLEKHA5, PLEKHA6, and PLEKHA7 bind to PDZD11 to target the Menkes ATPase ATP7A to the cell periphery and regulate copper homeostasis
journal, November 2021
- Sluysmans, Sophie; Méan, Isabelle; Xiao, Tong
- Molecular Biology of the Cell, Vol. 32, Issue 21
A Single PDZ Domain Protein Interacts with the Menkes Copper ATPase, ATP7A
journal, September 2005
- Stephenson, Sarah E. M.; Dubach, Daphne; Lim, Chris M.
- Journal of Biological Chemistry, Vol. 280, Issue 39
Enteric dysbiosis and fecal calprotectin expression in premature infants
journal, December 2018
- Ho, Thao T. B.; Groer, Maureen W.; Kane, Bradley
- Pediatric Research, Vol. 85, Issue 3
Antimicrobial activity of metals: mechanisms, molecular targets and applications
journal, May 2013
- Lemire, Joseph A.; Harrison, Joe J.; Turner, Raymond J.
- Nature Reviews Microbiology, Vol. 11, Issue 6
The composition of the gut microbiota throughout life, with an emphasis on early life
journal, February 2015
- Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine
- Microbial Ecology in Health & Disease, Vol. 26, Issue 0
eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
journal, November 2018
- Huerta-Cepas, Jaime; Szklarczyk, Damian; Heller, Davide
- Nucleic Acids Research, Vol. 47, Issue D1
The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity
journal, May 2009
- Macomber, L.; Imlay, J. A.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 20
CharmeRT: Boosting Peptide Identifications by Chimeric Spectra Identification and Retention Time Prediction
journal, June 2018
- Dorfer, Viktoria; Maltsev, Sergey; Winkler, Stephan
- Journal of Proteome Research, Vol. 17, Issue 8
Ménage à trois in the human gut: interactions between host, bacteria and phages
journal, May 2017
- Mirzaei, Mohammadali Khan; Maurice, Corinne F.
- Nature Reviews Microbiology, Vol. 15, Issue 7
The copper regulon of the human fungal pathogen Cryptococcus neoformans H99
journal, August 2011
- Ding, Chen; Yin, Jun; Tovar, Edgar Mauricio Medina
- Molecular Microbiology, Vol. 81, Issue 6
Heavy Metal Resistance Genes Are Associated with
bla
NDM-1
- and
bla
CTX-M-15
-Carrying Enterobacteriaceae
journal, May 2018
- Yang, Qiu E.; Agouri, Siham Rajab; Tyrrell, Jonathan Mark
- Antimicrobial Agents and Chemotherapy, Vol. 62, Issue 5
Maturation of the preterm gastrointestinal tract can be defined by host and microbial markers for digestion and barrier defense
journal, June 2021
- Henderickx, Jannie G. E.; Zwittink, Romy D.; Renes, Ingrid B.
- Scientific Reports, Vol. 11, Issue 1
Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants
journal, June 2019
- Gopalakrishna, Kathyayini P.; Macadangdang, Benjamin R.; Rogers, Matthew B.
- Nature Medicine, Vol. 25, Issue 7
Extended-spectrum β-lactamase characterisation and heavy metal resistance of Enterobacteriaceae strains isolated from hospital environmental surfaces
journal, May 2010
- Touati, A.; Zenati, K.; Brasme, L.
- Journal of Hospital Infection, Vol. 75, Issue 1
Selection and dissemination of antimicrobial resistance in Agri-food production
journal, October 2019
- Cheng, Guyue; Ning, Jianan; Ahmed, Saeed
- Antimicrobial Resistance & Infection Control, Vol. 8, Issue 1
High frequencies of antibiotic resistance genes in infants’ meconium and early fecal samples
journal, September 2015
- Gosalbes, M. J.; Vallès, Y.; Jiménez-Hernández, N.
- Journal of Developmental Origins of Health and Disease, Vol. 7, Issue 1
tcrB, a Gene Conferring Transferable Copper Resistance in Enterococcus faecium: Occurrence, Transferability, and Linkage to Macrolide and Glycopeptide Resistance
journal, May 2002
- Hasman, Henrik; Aarestrup, Frank M.
- Antimicrobial Agents and Chemotherapy, Vol. 46, Issue 5
Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors
journal, June 2020
- Chen, Yuhao; Brook, Thomas C.; Soe, Cho Zin
- Microbial Genomics, Vol. 6, Issue 6
Microbial Copper-binding Siderophores at the Host-Pathogen Interface
journal, July 2015
- Koh, Eun-Ik; Henderson, Jeffrey P.
- Journal of Biological Chemistry, Vol. 290, Issue 31
Parsing the functional specificity of Siderocalin/Lipocalin 2/NGAL for siderophores and related small-molecule ligands
journal, April 2019
- Clifton, Matthew C.; Rupert, Peter B.; Hoette, Trisha M.
- Journal of Structural Biology: X, Vol. 2
The immune consequences of preterm birth
journal, January 2013
- Melville, Jacqueline M.; Moss, Timothy J. M.
- Frontiers in Neuroscience, Vol. 7
Copper Transport and Trafficking at the Host–Bacterial Pathogen Interface
journal, October 2014
- Fu, Yue; Chang, Feng-Ming James; Giedroc, David P.
- Accounts of Chemical Research, Vol. 47, Issue 12
Clinical implications of preterm infant gut microbiome development
journal, December 2021
- Healy, David B.; Ryan, C. Anthony; Ross, R. Paul
- Nature Microbiology, Vol. 7, Issue 1
Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life
journal, July 2017
- Xiong, Weili; Brown, Christopher T.; Morowitz, Michael J.
- Microbiome, Vol. 5, Issue 1
A genome-wide screen reveals the involvement of enterobactin-mediated iron acquisition inEscherichia colisurvival during copper stress
journal, August 2021
- Casanova-Hampton, Kaitlin; Carey, Alexis; Kassam, Sarah
- Metallomics, Vol. 13, Issue 9
Selection of resistance by antimicrobial coatings in the healthcare setting
journal, September 2020
- Pietsch, F.; O'Neill, A. J.; Ivask, A.
- Journal of Hospital Infection, Vol. 106, Issue 1