SARS-CoV-2 and Emerging Foodborne Pathogens: Intriguing Commonalities and Obvious Differences

Abstract

The coronavirus disease 2019 (COVID-19) has resulted in tremendous human and economic losses around the globe. The pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that is closely related to SARS-CoV and other human and animal coronaviruses. Although foodborne diseases are rarely of pandemic proportions, some of the causative agents emerge in a manner remarkably similar to what was observed recently with SARS-CoV-2. For example, Shiga toxin-producing Escherichia coli (STEC), the most common cause of hemolytic uremic syndrome, shares evolution, pathogenesis, and immune evasion similarities with SARS-CoV-2. Both agents evolved over time in animal hosts, and during infection, they bind to specific receptors on the host cell's membrane and develop host adaptation mechanisms. Mechanisms such as point mutations and gene loss/genetic acquisition are the main driving forces for the evolution of SARS-CoV-2 and STEC. Both pathogens affect multiple body organs, and the resulting diseases are not completely cured with non-vaccine therapeutics. However, SARS-CoV-2 and STEC obviously differ in the nature of the infectious agent (i.e., virus vs. bacterium), disease epidemiological details (e.g., transmission vehicle and symptoms onset time), and disease severity. SARS-CoV-2 triggered a global pandemic while STEC led to limited, but sometimes serious, disease outbreaks. The current review compares several key aspects of these two pathogenic agents, including the underlying mechanisms of emergence, the driving forces for evolution, pathogenic mechanisms, and the host immune responses. We ask what can be learned from the emergence of both infectious agents in order to alleviate future outbreaks or pandemics.

Keywords: COVID-19; SARS-CoV-2; Shiga toxin; Shiga toxin-producing Escherichia coli; infectious diseases.

Figure 1

Evolution of Shiga toxin-producing Escherichia coli (STEC) O157:H7. A1–A6 represent clonal complexes originating from the ancestral clone O55:H7 to the typical Shiga toxin-producing E. coli O157:H7. Abbreviations: SOR, sorbitol fermenting ability; GUD, glucuronidase activity; LEE, locus of enterocyte effacement; Stx1, Shiga toxin 1; Stx2, Shiga toxin 2. The figure was adapted from [58] and created using Biorender.com.

Figure 2

SARS-CoV-2 genome, which shows single-stranded RNA that encodes open reading frames (ORFs) 1a and 1b, spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Three-dimensional structure (protein database ID number 6VW1) for the receptor-binding domain (RBD) interacting with the human angiotensin converting enzyme (ACE2) receptor is illustrated. The figure is adapted from [63] and created using Biorender.com.

Figure 4

The mode of action of Shiga toxin. (1) Initial contact of Shiga toxin-producing Escherichia coli (STEC) with enterocyte. (2) Attachment of STEC to the cell via intimin and Tir protein interaction, and actin polymerization. (3) Production of Shiga toxin. (4) Binding of Shiga toxin to globotriaosylceramide (Gb3) receptor. (5) Endocytosis of Shiga toxin into the enterocyte via vesicle formation. (6) Transport of the Shiga toxin to the Golgi apparatus, then to the endoplasmic reticulum. (7) Release of the Shiga toxin subunit A, which acts as N-glycosidase by removing adenine from the ribosomal 28s RNA; this abolishes translation of the mRNA by the ribosome, halting protein synthesis and leading to cell death (8). The figure was created using Biorender.com.

Figure 5

Infection of the mammalian cell by SARS-CoV-2 and virions multiplication. Initially, the virus binds to an angiotensin converting enzyme (ACE2) receptor on the cell surface, followed by processing of the viral S protein by host proteases, leading to the fusion of the viral envelope and host cell membrane. Thereafter, the viral genomic RNA is deposited into the host cell cytoplasm and translated by the host translation system. The resulting viral polypeptide is cleaved by proteases encoded on the polypeptide itself, and the cleaved components generate RNA polymerase complex. The latter uses the virus RNA genome (+ sense) as a template to generate negative-sense RNA genomes and subgenomic RNA regions before both types of RNA serve as templates for synthesis of positive-sense full-length RNA genome and subgenomic mRNAs. These mRNAs act as templates for the synthesis of structural and accessory proteins, which decorate the viral nucleocapsid. The whole transcription and translation process of the viral subgenomic RNA and replication of the full-length RNA genome occur in the convoluted endoplasmic reticulum membranes. Finally, the full-length (+ sense) RNA genome binds to the nucleocapsid prior to full assembly of the virion, which eventually is released from the cell via exocytosis. Protein abbreviations: E, envelop; M, membrane; N, nucleocapsid; NSPS, non-structural; S, spike. The figure was adapted from [106] and created using Biorender.com.

Figure 6

Evasion of interferon (IFN) pathways by SARS-CoV-2. The IFN responses start by sensing the viral RNA by pattern recognition receptors (PRRs, e.g., retinoic acid-inducible gene I (RIG-1)) and melanoma differentiation-associated protein 5 (MDA-5), which mediate signal transduction via the adaptor complex of the mitochondrial antiviral-signaling protein (MAVS). The PRR–adaptor interaction recruits kinases that phosphorylate interferon regulatory factor 3/7 (IRF3/7) and the nuclear factor-kB (NF-kB); these are transcriptional factors that enter the nucleus and transcribe IFNs. The IFNs act as a signal through Janus kinase 1 (JAK1) and the signal transducer and activator of transcription 1 and 2 (STAT1/2), resulting in the transcription of IFN-stimulated genes (ISGs), which exhibit antiviral effects. SARS-CoV-2 proteins encoded by open reading frame (ORF) 6 and 9c and several nonstructural proteins (Nsps) inhibit these pathways and render the virus resistant to IFN responses. The figure was adapted from [106] and created using Biorender.com.

Figure 3

Variants of concern of SARS-CoV-2 as of February 2022. Variants are caused by single nucleotide polymorphisms (SNPs) at particular sites on the spike protein, resulting in changes in the amino acid residues at these sites. For example, a variant where arginine (R) is substituted for leucine (L) at residue 452 is denoted by L452R. Another variant is caused by the deletion of the H69/V70 site. The amino acid residues shown are C, D, E, G, H, I, K, L, N, P, Q, R, S, T, V, W, and Y, which denotes for cysteine, aspartic acid, glutamic acid, glycine, histidine, isoleucine, lysine, leucine, asparagine, proline, glutamine, arginine, serine, threonine, valine, tryptophan, and tyrosine, respectively. Key mutations for each variant are presented and only the most recent omicron variants (BA.2.12.1, BA.4, and BA.5) with highest transmissibility are illustrated. The figure was created using Biorender.com.