Bacterial Genetics for the USMLE Step 1

Summary

This microbiology lecture explores bacterial genetics and the mechanisms by which bacteria can undergo genetic changes to increase virulence or antibiotic resistance. Topics covered include random mutations, phase and antigenic variation, transformation, conjugation, and transduction. The lecture highlights how these genetic changes can occur both vertically (from parent to progeny) and horizontally (between bacteria), significantly impacting bacterial survival and pathogenicity. Additionally, the concept of restriction-modification systems and transposable elements is discussed, showcasing how bacteria can acquire and lose genetic traits that enhance or diminish virulence.

Takeaways

• 🧬 Random mutation is a slow, vertical genetic change where spontaneous DNA alterations are passed to progeny and can gradually increase virulence or antibiotic resistance.
• 🔀 Phase and antigenic variation involve rapidly turning genes on or off without mutation, enabling quick changes to structures like pili, capsules, or antigens to evade immune detection.
• 📥 Transformation is a fast, horizontal gene transfer method in which competent bacteria take up naked DNA from lysed cells, potentially acquiring new virulence traits.
• 🔗 Conjugation uses plasmids and a sex pilus to transfer genetic material horizontally, often spreading antibiotic resistance genes efficiently.
• 🧪 Hfr (high-frequency recombination) cells form when plasmids integrate into the bacterial chromosome, allowing transfer of chromosomal genes and creation of recombinant bacteria.
• 📦 Transduction uses bacteriophages to transfer DNA; generalized transduction transfers random bacterial DNA during the lytic cycle, while specialized transduction transfers specific genes—often exotoxin genes—during lysogenic conversion.
• 🛡️ The restriction-modification system protects bacteria from viral DNA by using restriction endonucleases to degrade foreign DNA while methylating their own DNA to avoid self-destruction.
• 🚀 Transposable elements (transposons) are mobile DNA segments that can jump between plasmids and chromosomes, contributing to multidrug resistance when many resistance genes accumulate on a single plasmid.
• 📉 Lack of selective pressure can lead bacteria to lose plasmids that no longer provide an advantage, resulting in decreased virulence or loss of antibiotic resistance.
• 🧪 Exam-style identification requires recognizing genetic mechanisms from descriptions, such as distinguishing vertical vs. horizontal transfer or spotting fast vs. slow genetic changes.
• 🎯 The example question demonstrates phase variation: a single bacterium quickly turns on a gene (producing a slime layer), passes it to progeny, and becomes more abundant due to a selective advantage.

Q & A

What is the main difference between vertical and horizontal genetic change in bacteria?

Vertical genetic change is passed from a parent bacterium to its progeny (e.g., random mutation, phase/antigenic variation), while horizontal genetic change is acquired from nearby bacteria or viruses (e.g., transformation, conjugation, transduction).

Why do random mutations typically occur slowly?

Random mutations involve spontaneous, infrequent changes to the genome, and only a small portion of these mutations benefit the bacterium. Accumulating advantageous mutations takes time.

How does phase or antigenic variation increase bacterial virulence?

Phase and antigenic variation rapidly turn genes on or off without altering the DNA sequence. This can change surface structures such as pili, capsules, or antigens, helping the bacterium evade immune detection and survive better.

What is required for transformation to occur?

Transformation requires the presence of naked DNA from lysed bacteria and a competent bacterium capable of taking up and integrating that DNA. Key competent species include Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b.

What distinguishes F+ cells from F– cells in conjugation?

F+ cells contain a plasmid with genes for the sex pilus (the fertility factor), enabling them to transfer genetic material to F– cells. F– cells lack this plasmid and cannot initiate conjugation without first receiving it.

What is an Hfr cell and why is it significant?

An Hfr cell is a bacterium where the F plasmid has integrated into the chromosome. It can transfer chromosomal genes at high frequency during conjugation, creating new gene combinations in recipient cells.

How do generalized and specialized transduction differ?

Generalized transduction involves accidental packaging of random bacterial DNA into bacteriophage capsids during the lytic cycle, while specialized transduction transfers specific bacterial genes adjacent to prophage insertion sites during lysogenic conversion.

What is lysogenic conversion and why is it clinically important?

Lysogenic conversion occurs when a bacterium acquires new genes from an integrated bacteriophage. These genes may encode exotoxins such as diphtheria toxin, cholera toxin, and botulinum toxin, significantly increasing bacterial virulence.

What role do restriction endonucleases play in bacterial defense?

Restriction endonucleases degrade invading viral DNA to prevent phage takeover. Bacteria protect their own DNA through methylation of restriction sites; if methylation fails, both viral and bacterial DNA are degraded, killing the cell.

How do transposable elements contribute to antibiotic resistance?

Transposons can move resistance genes between plasmids and chromosomes. Multiple transposons may accumulate on a single plasmid, creating multidrug-resistant plasmids that can spread through conjugation.

How can bacteria lose virulence in the absence of selective pressure?

Without selective pressure, bacteria may discard energetically costly genetic material—often plasmids—if these genes no longer provide a survival advantage, leading to decreased virulence or antibiotic resistance.

Why was phase variation the correct answer in the example question about slime layer production?

The slime layer appeared suddenly in a single bacterium of the first generation and conferred an advantage. Such rapid activation of pre-existing genes is consistent with phase variation, not slow mutation or horizontal gene transfer.