Topic V: Bacterial Genetics & Exchange of Genetic Information

What is antibiotic resistance?

• Occurs at the genetic level

• Resistance can arise in 2 ways:

  • Vertical transmission- from parent to daughter cells

  • Horizontal transmission- b/w unrelated bacteria

• Since bacteria are haploid (1 copy of their chromosome), any mutation or new gene is expressed immediately

How do bacteria naturally produce spontaneous mutations?

• Due to errors by DNA polymerase during replication of genome

• Mutations are at random throughout genome

What happens to mutations that are beneficial to bacteria?

Maintained in the population

• Provide a selective advantage

  • Antibiotic resistance, toxic expression

• Mutations that do not confer a benefit are lost

What are there many chances for since bacteria replicate so quickly?

Create beneficial mutations

What can mutations in DNA lead to?

A change in the amino acid sequence

What is a silent mutation?

No change in amino acid sequence

What is a missense mutation?

1 base substitution → 1 amino acid change

What is a nonsense mutation?

Early termination of peptide chain

What is the other mutation?

Frameshift mutation

What are transposons?

Segments of DNA that move from 1 site on a DNA molecule to another

• Can create mutations when they move (on ends of cut DNA)

• Can include genes for antibiotic resistance

• Can “jump” b/w chromosomes & plasmids (& vice versa)

If a bacteria creates a mutation, how can it be trasnferred to other bacteria?

3 mechanisms of gene transfer

• Bacterial transformation

• Bacterial transduction

• Bacterial conjugation

What can bacterai share genes for?

Virulence factors

• Enzymes

  • Cleavage of antibiotics

• Membrane proteins

  • For efflux of antibiotics

• Also exotoxins & adhesive factors (pili)

What is gene transfer?

Unidirectional

• Donor to recipient

  • Not “swapping” genes

• Does not donate entire chromosome

• Can occur b/w different species of bacteria

What is transformation?

• Relatively rare form of genetic transfer

• Requires 2 steps:

  • Uptake of DNA from environment

  • Recombine or insert new DNA into chromosome

• DNA must be integrated into host chromosome

  • Linear DNA is broken down quickly by bacteria

  • New DNA must be integrated into genome

What is conjugation?

• Gene transfer from a donor to a recipient to by direct physical contact b/w cells

• Donor bacteria forms a sex pilus to pull bacteria close together

  • Transfers plasmid (or sometimes a piece of chromosome) to recipient

What is the factor in conjugation?

F-factor → donor

• “Fertility factor”

• Plasmid from donor bacteria that includes the genes for sex pilus

What happens in conjugation after donor transfers plasmid to recipient bacteria?

• New DNA may be degraded, & fragmented inserted into genome, or

• Maintained as a plasmid

Recipient is now able to pass plasmid onto other bacteria

What is transduction?

Transfer of genetic information by bacteriophages

• Bacteriophage can carry bacterial DNA from 1 bacteria to another

What is generalized transduction?

Phage carries just bacterial DNA

What is specialized transduction?

Phage carries some bacterial & some viral DNA

What is Staphylococcus aureus?

Common Gm+ bacteria

What is MSSA?

Methicillin-sensitive S. aureus

What is MRSA?

Methicillin-resistant S. aureus

• Resistant to many forms of penicillin

  • Acquired a gene for “penicillin binding protein-2a” (PBP2a)

    • Encodes for a transpeptidase that does not bind to penicillins

  • First reported in 1968 in US

  • Formed from a combination of plasmids & trsanposons

What is MRSA often treated w/?

Vancomycin

• “Drug of last resort”

What is VRSA?

Vancomycin-resistant S. aureus

• Picked up a vancomycin-resistance gene from a different bacteria in the gut

• First reported in 2002 in US

What can bacteria acquire multiple?

Resistance genes

• ESBL plasmid: extended spectrum beta-lactamase

  • can cleave many types of penicillin

• NDM1: New Delhi metallo-beta-lactamase type 1

  • First discovered in India in 2009, but was soon found to be more widespread

  • First case in US in June 2010

• Both are increasingly common in E. coli & Klebsiella pneumoniae