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Cited by 8Bacterial Genetics and BiotechnologyEscherichia coli research studiesAntibiotic Resistance in Bacteria

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Inactivation of genes in oxidative respiration and iron acquisition pathways in pediatric clinical isolates of Small colony variant Enterobacteriaceae

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Greninger, Alexander L., Addetia, Amin, Tao, Yue, Adler, Amanda, Qin, Xuan·2021·Scientific Reports
DOI 10.1038/s41598-021-86764-4PMC PMC8018945

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Abstract

Isolation of bacterial small colony variants (SCVs) from clinical specimens is not uncommon and can fundamentally change the outcome of the associated infections. Bacterial SCVs often emerge with their normal colony phenotype (NCV) co-isolates in the same sample. The basis of SCV emergence in vivo is not well understood in Gram-negative bacteria. In this study, we interrogated the causal genetic lesions of SCV growth in three pairs of NCV and SCV co-isolates of Escherichia coli , Citrobacter freundii , and Enterobacter hormaechei . We confirmed SCV emergence was attributed to limited genomic mutations: 4 single nucleotide variants in the E. coli SCV, 5 in C. freundii , and 8 in E. hormaechei . In addition, a 10.2 kb chromosomal segment containing 11 genes was deleted in the E. hormaechei SCV isolate. Each SCV had at least one coding change in a gene associated with bacterial oxidative respiration and another involved in iron capture. Chemical and genetic rescue confirmed defects in heme biosynthesis for E. coli and C. freundii and lipoic acid biosynthesis in E. hormaachei were responsible for the SCV phenotype. Prototrophic growth in all 3 SCV Enterobacteriaceae species was unaffected under anaerobic culture conditions in vitro, illustrating how SCVs may persist in vivo.

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Metadata

Authors
Greninger, A. L., Addetia, A., Tao, Y., Adler, A., & Qin, X.
Affiliations
  • Seattle Children's Hospital (US)
  • Shanghai Jiao Tong University (CN)
Corresponding author
Qin, Xuan
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-04-02
Volume
11
Issue
1
Pages
7457-7457
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-86764-4
PMC
PMC8018945
OpenAlex
W3145054816
Cited by
8
References
6
Citations by year
2026: 1 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 2
FWCI
0.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
Keywords
small colony variants, Enterobacteriaceae, Escherichia coli, Citrobacter freundii, Enterobacter hormaechei, oxidative respiration, iron acquisition, heme biosynthesis, lipoic acid biosynthesis, single nucleotide variants, chromosomal deletion, genetic rescue, anaerobic growth, Gram-negative bacteria
MeSH terms
Whole Genome Sequencing, Aerobiosis, Anaerobiosis, Child, Enterobacteriaceae, Female, Genes, Bacterial, Heme, Humans, Infant, Iron, Kinetics, Thioctic Acid, Male, Microbial Sensitivity Tests, Phenotype, Genetic Variation, Colony Count, Microbial, Gene Silencing, Drug Resistance, Bacterial, Biosynthetic Pathways

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