Understanding the Human Microbiome: A Student's Guide
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12 cards
Question: How can human oncoviruses drive carcinogenesis in host cells?
Answer: By integrating their oncogenes into host genomes or expressing viral oncoproteins that block tumour suppressor proteins (e.g., HPV E6 and E7 block p53
Question: Which HPV oncoproteins block p53 and RB protein function?
Answer: E6 and E7.
Question: Name microbial factors that can directly cause double-stranded DNA damage in mammalian cells.
Answer: Colibactin (from pks+ E. coli and some Enterobacteriaceae) and cytolethal distending toxin (CDT) produced by several Escherichia coli and other ε- and
Question: Which bacterial toxins can indirectly damage human DNA by generating reactive oxygen species?
Answer: Bacteroides fragilis toxin (BFT) from enterotoxigenic B. fragilis induces high levels of reactive oxygen species that in turn damage host DNA.
Question: List bacterial factors that alter host cell cycle or signaling relevant to carcinogenesis.
Answer: Cytotoxic necrotizing factor (CNF) produced by several E. coli and cycle inhibiting factor (Cif) produced by EPEC and EHEC.
Question: What specific DNA changes does colibactin induce in exposed human cells?
Answer: Colibactin modifies adenine nucleotides causing double-stranded DNA damage; it yields characteristic mutations including single-base substitutions (SB
Question: How was evidence obtained that colibactin-associated mutations occur in human colorectal cancer (CRC)?
Answer: Whole-genome sequencing of human CRC tumours revealed a subset with mutations characteristic of colibactin exposure (SBS-pks and ID-pks), suggesting t
Question: Under what intestinal conditions do pks+ E. coli promote tumorigenesis more readily?
Answer: In an inflamed intestine, where shifts in oxygen levels and inflammatory signaling (e.g., NF-κB and IL-6) create a pro-tumorigenic environment that pr
Question: How does epithelial hypoxia normally get maintained in the healthy intestine and why does this matter for microbiota composition?
Answer: PPAR-γ expression in intestinal epithelial cells activates mitochondrial bioenergetics that consume O2, maintaining epithelial hypoxia (<1%), which su
Question: What role does NF-κB play in the transition from intestinal inflammation to malignancy?
Answer: NF-κB induces IL-6, which promotes intestinal epithelial cell proliferation, inhibits apoptosis, and activates other pro-tumorigenic pathways.