Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques

Background: Many Escherichia coli strains are considered to be a component of the normal flora found in the human and animal intestinal tracts. While most E. coli strains are commensal, some strains encode virulence factors that enable the bacteria to cause intestinal and extra-intestinal clinically...

Full description

Bibliographic Details
Main Authors: Feng, Yan, Mannion, Anthony, Madden, Carolyn, Swennes, Alton G., Townes, Catherine, Byrd, Charles, Marini, Robert P, Fox, James G
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:English
Published: BioMed Central 2018
Online Access:http://hdl.handle.net/1721.1/113343
https://orcid.org/0000-0001-9307-6116
_version_ 1811094303461605376
author Feng, Yan
Mannion, Anthony
Madden, Carolyn
Swennes, Alton G.
Townes, Catherine
Byrd, Charles
Marini, Robert P
Fox, James G
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
Feng, Yan
Mannion, Anthony
Madden, Carolyn
Swennes, Alton G.
Townes, Catherine
Byrd, Charles
Marini, Robert P
Fox, James G
author_sort Feng, Yan
collection MIT
description Background: Many Escherichia coli strains are considered to be a component of the normal flora found in the human and animal intestinal tracts. While most E. coli strains are commensal, some strains encode virulence factors that enable the bacteria to cause intestinal and extra-intestinal clinically-relevant infections. Colibactin, encoded by a genomic island (pks island), and cytotoxic necrotizing factor (CNF), encoded by the cnf gene, are genotoxic and can modulate cellular differentiation, apoptosis and proliferation. Some commensal and pathogenic pks+ and cnf+ E. coli strains have been associated with inflammation and cancer in humans and animals. Results: In the present study, E. coli strains encoding colibactin and CNF were identified in macaque samples. We performed bacterial cultures utilizing rectal swabs and extra-intestinal samples from clinically normal macaques. A total of 239 E. coli strains were isolated from 266 macaques. The strains were identified biochemically and selected isolates were serotyped as O88:H4, O25:H4, O7:H7, OM:H14, and OM:H16. Specific PCR for pks and cnf1 gene amplification, and phylogenetic group identification were performed on all E. coli strains. Among the 239 isolates, 41 (17.2%) were pks+/cnf1−, 19 (7.9%) were pks−/cnf1+, and 31 (13.0%) were pks+/cnf1+. One hundred forty-eight (61.9%) E. coli isolates were negative for both genes (pks−/cnf1−). In total, 72 (30.1%) were positive for pks genes, and 50 (20.9%) were positive for cnf1. No cnf2+ isolates were detected. Both pks+ and cnf1+ E. coli strains belonged mainly to phylogenetic group B2, including B21. Colibactin and CNF cytotoxic activities were observed using a HeLa cell cytotoxicity assay in representative isolates. Whole genome sequencing of 10 representative E. coli strains confirmed the presence of virulence factors and antibiotic resistance genes in rhesus macaque E. coli isolates. Conclusions: Our findings indicate that colibactin- and CNF-encoding E. coli colonize laboratory macaques and can potentially cause clinical and subclinical diseases that impact macaque models.
first_indexed 2024-09-23T15:57:53Z
format Article
id mit-1721.1/113343
institution Massachusetts Institute of Technology
language English
last_indexed 2024-09-23T15:57:53Z
publishDate 2018
publisher BioMed Central
record_format dspace
spelling mit-1721.1/1133432022-09-29T17:21:19Z Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques Feng, Yan Mannion, Anthony Madden, Carolyn Swennes, Alton G. Townes, Catherine Byrd, Charles Marini, Robert P Fox, James G Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Feng, Yan Mannion, Anthony Madden, Carolyn Swennes, Alton G. Townes, Catherine Byrd, Charles Marini, Robert P Fox, James G Background: Many Escherichia coli strains are considered to be a component of the normal flora found in the human and animal intestinal tracts. While most E. coli strains are commensal, some strains encode virulence factors that enable the bacteria to cause intestinal and extra-intestinal clinically-relevant infections. Colibactin, encoded by a genomic island (pks island), and cytotoxic necrotizing factor (CNF), encoded by the cnf gene, are genotoxic and can modulate cellular differentiation, apoptosis and proliferation. Some commensal and pathogenic pks+ and cnf+ E. coli strains have been associated with inflammation and cancer in humans and animals. Results: In the present study, E. coli strains encoding colibactin and CNF were identified in macaque samples. We performed bacterial cultures utilizing rectal swabs and extra-intestinal samples from clinically normal macaques. A total of 239 E. coli strains were isolated from 266 macaques. The strains were identified biochemically and selected isolates were serotyped as O88:H4, O25:H4, O7:H7, OM:H14, and OM:H16. Specific PCR for pks and cnf1 gene amplification, and phylogenetic group identification were performed on all E. coli strains. Among the 239 isolates, 41 (17.2%) were pks+/cnf1−, 19 (7.9%) were pks−/cnf1+, and 31 (13.0%) were pks+/cnf1+. One hundred forty-eight (61.9%) E. coli isolates were negative for both genes (pks−/cnf1−). In total, 72 (30.1%) were positive for pks genes, and 50 (20.9%) were positive for cnf1. No cnf2+ isolates were detected. Both pks+ and cnf1+ E. coli strains belonged mainly to phylogenetic group B2, including B21. Colibactin and CNF cytotoxic activities were observed using a HeLa cell cytotoxicity assay in representative isolates. Whole genome sequencing of 10 representative E. coli strains confirmed the presence of virulence factors and antibiotic resistance genes in rhesus macaque E. coli isolates. Conclusions: Our findings indicate that colibactin- and CNF-encoding E. coli colonize laboratory macaques and can potentially cause clinical and subclinical diseases that impact macaque models. 2018-01-30T15:33:46Z 2018-01-30T15:33:46Z 2017-12 2017-10 2017-12-10T04:58:12Z Article http://purl.org/eprint/type/JournalArticle 1757-4749 http://hdl.handle.net/1721.1/113343 Feng, Yan, et al. “Cytotoxic Escherichia Coli Strains Encoding Colibactin and Cytotoxic Necrotizing Factor (CNF) Colonize Laboratory Macaques.” Gut Pathogens, vol. 9, no. 1, Dec. 2017. https://orcid.org/0000-0001-9307-6116 en http://dx.doi.org/10.1186/s13099-017-0220-y Gut Pathogens Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf BioMed Central BioMed Central
spellingShingle Feng, Yan
Mannion, Anthony
Madden, Carolyn
Swennes, Alton G.
Townes, Catherine
Byrd, Charles
Marini, Robert P
Fox, James G
Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques
title Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques
title_full Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques
title_fullStr Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques
title_full_unstemmed Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques
title_short Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques
title_sort cytotoxic escherichia coli strains encoding colibactin and cytotoxic necrotizing factor cnf colonize laboratory macaques
url http://hdl.handle.net/1721.1/113343
https://orcid.org/0000-0001-9307-6116
work_keys_str_mv AT fengyan cytotoxicescherichiacolistrainsencodingcolibactinandcytotoxicnecrotizingfactorcnfcolonizelaboratorymacaques
AT mannionanthony cytotoxicescherichiacolistrainsencodingcolibactinandcytotoxicnecrotizingfactorcnfcolonizelaboratorymacaques
AT maddencarolyn cytotoxicescherichiacolistrainsencodingcolibactinandcytotoxicnecrotizingfactorcnfcolonizelaboratorymacaques
AT swennesaltong cytotoxicescherichiacolistrainsencodingcolibactinandcytotoxicnecrotizingfactorcnfcolonizelaboratorymacaques
AT townescatherine cytotoxicescherichiacolistrainsencodingcolibactinandcytotoxicnecrotizingfactorcnfcolonizelaboratorymacaques
AT byrdcharles cytotoxicescherichiacolistrainsencodingcolibactinandcytotoxicnecrotizingfactorcnfcolonizelaboratorymacaques
AT marinirobertp cytotoxicescherichiacolistrainsencodingcolibactinandcytotoxicnecrotizingfactorcnfcolonizelaboratorymacaques
AT foxjamesg cytotoxicescherichiacolistrainsencodingcolibactinandcytotoxicnecrotizingfactorcnfcolonizelaboratorymacaques