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

Abstract

BackgroundMany 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.ResultsIn 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.ConclusionsOur findings indicate that colibactin- and CNF-encoding E. coli colonize laboratory macaques and can potentially cause clinical and subclinical diseases that impact macaque models.Electronic supplementary materialThe online version of this article (10.1186/s13099-017-0220-y) contains supplementary material, which is available to authorized users.

Genomic diversity of Escherichia coli isolates from non-human primates in the Gambia

“… E. coli strains encoding colibactin, or cytotoxic necrotizing factor 1 have been isolated from healthy laboratory rhesus macaques [6], while enteropathogenic E. coli strains can – in the laboratory – cause colitis in marmosets [7], rhesus macaques infected with simian immunodeficiency virus [8] and cotton-top tamarins [9].…”

Prevalence and pathologic effects of colibactin and cytotoxic necrotizing factor-1 (Cnf 1) in Escherichia coli: experimental and bioinformatics analyses

“…Such predominance of the pks island among the Enterobacteriaceae family suggested the spread of this PAI via horizontal gene transfer [5]. Interestingly, a strong association was noticed between the production of colibactin by ExPEC and other virulence determinants including the adhesions determinants, production of hemolysin (β-hemolytic activity), cytotoxins such as the Cnfs and siderophores such as Yersiniabactin [2, 6, 15–17]. In 2017, the prevalence and association between the β-hemolytic activity, Cnf 1 and colibactin production among E. coli strains phylogroup B2 that colonize the macaques has reached 100%, 97.7% and 100%, respectively [17].…”

Characterization ofCampylobacter jejuni, Campylobacter upsaliensis,and a novelCampylobacter sp. in a captive non‐human primate zoological collection

“…A novel Campylobacter sp. genome (MIT 12‐8780) was sequenced as described previously using Illumina MiSeq with 2× 300 bp reads . Raw sequencing reads were decontaminated of adapter sequences and quality trimmed to a Phred quality score (Q) ≥10 using BBDuk from the BBMap package, followed by de novo assembly using SPAdes and gene annotation with RAST, both hosted by PATRIC .…”

“…Campylobacter spp. can colonize asymptomatic monkeys or cause gastrointestinal disease in non‐human primates in addition to other enteric pathogenic agents such as Shigella spp., Salmonella spp., and Escherichia coli . Historically, the primate collection at the Como Park Zoo in Saint Paul, MN, has experienced diarrheal illnesses and associated mortality.…”