O'Donnell Bacterial Genetics

How does antibiotic resistance arise?

Occurs at the genetic level in two ways:

• Vertical transmission (mutations)

• Horizontal transmission (gene transfer)

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

Vertical Transmission

Passing down a genetic mutation to both daughter cell via cell division

Horizontal Transmission

Passing plasmid to neighboring bacteria

• Can occur between unrelated species of bacteria

Resistance to rifampin can be caused by _____

Spontaneous mutations in RNA polymerase

Silent Mutation

No change in the amino acid sequence

Missense Mutation

One base substitution that changes an amino acid

Nonsense Mutation

Early termination (early stop codon)

Frameshift Mutation

Add or delete one nucleotide

Transposon

Segment of DNA that moves from one site on a DNA molecule to another

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

• Can include genes for antibiotic resistance

• Can “jump” between chromosomes and plasmids

Bacterial gene transfer

Allows bacteria to share genes for virulence factors:

• Enzymes (Breakdown of antibiotics)

• Membrane proteins (For efflux of antibiotics)

• Exotoxins

• Adhesive factors

Unidirectional

• Donor to receipient only, NOT swapping genes

• Donates plasmid or chromosome fragment, NOT entire chromosome

Can occur between different species of bacteria

Transformation

Relatively rare form of genetic transfer that requires two steps:

1. Uptake of DNA from environment

2. Recombination into the host chromosome

DNA must be intergrated into the host chromosome before it is degraded

• Bacteria quickly break down linear DNA

Conjugation

Gene transfer from a donor to a recipient by direct physical contact

Donor bacteria forms a sex pilus to pull bacteria close together

Transfers plasmid and sometimes a piece of chromosome

Type IV Secretion Bridge

Acts like a syringe to inject DNA into neighboring bacteria in the process of conjugation

• Very short, so bacteria need to be close together

F-factor

Fertility factor

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

If the fertility factor is shared, the recipient is able to pass the plasmid to other bacteria

What happens when a donor transfers a plasmid to another bacteria during conjugation?

Plasmid can be:

• Degraded, and fragments inserted into the genome

• Maintained as a plasmid

Transduction

Transfer of genetic information by bacteriophages, which can carry bacterial DNA from one bacteria to another

Two types:

• Generalized transduction

• Specialized transduction

Generalized Transduction

Phage carries just bacterial DNA

Specialized Transduction

Phage carries some bacterial and some viral DNA

MSSA

Methicillin-sensitive Staphylococcus aureus

MRSA

Methicillin-resistant Staphylococcus aureus

VRSA

Vancomycin-resistant Staphylococcus aureus

Clinical relevance of MRSA and VRSA

MRSA

• Resistant to many forms of penicillin

• Acquired gene for Penicillin Binding Protein-2a (PBP2a)

  • Transpeptidase that is resistant to penicillins

• Formed from a combination of plasmids and transposons

• Often treated with vancomycin (drug of last resort)

VRSA

• Picked up vancomycin-resistance gene from an unrelated bacteria

Resistance genes that are common in E. coli and Klebsiella pneumoniae

ESBL Plasmid (Extended spectrum β-lactamase)

• Can cleave many types of penicillin

NDM1 (New Delhi metallo-β-lactamase type 1)