Session 9: Microbial Adaptations

Microbial adaptations

Ability of microbes to endure selective pressures of their environment

How do bacteria replicate

Binary fission (asexual exponential reproduction) to produce clonally identical progeny

Difference between antibiotic & antimicrobial resistance

Antibiotic resistance refers specifically to resistance to bacteria.

Antimicrobial resistance refers to resistance to bacteria, viruses, fungi and parasites.

Bacteria become resistant to antibiotics in one of three ways...

1) Development of point mutations in one of target genes (micro-evolutionary change). Such as the alteration in the beta-lactamase gene extending its spectrum of activity against different beta-lactam antibiotics

2) Macro-evolutionary changes e.g., rearrangement of genes as might occur with acquisition of antibiotic bearing plasmids or transposons

3) Acquire DNA from exogeneous source e.g., naturally transformable species such as Neisseria can acquire DNA from its environment. It is posited that this is how Neisseria species acquire antibiotic resistant genes (e.g., penicillin).

Cross-resistance

Resistance to one antimicrobial agent because of its similarity to another antimicrobial agent

Example: aminoglycoside-modifying enzymes which may confer resistance to several members of the aminoglycoside family.

Co-resistance

Co-existence of multiple genes or mutations encoding resistance to different drugs within the same strain or genetic element.

Co-selection

Selection of multiple resistance genes when one of these genes is selected

Mechanisms of drug resistance

1) Drug inactivation

2) Prevent penetration to target site inside cell

3) Alteration of drug target site

4) Rapid efflux of drug

Mutations are ___ and can be located anywhere in the DNA. If the mutation gives the bacterium an advantage in a specific environment, this bacterium will thrive and grow better.

Mutations are random and can be located anywhere in the DNA. If the mutation gives the bacterium an advantage in a specific environment, this bacterium will thrive and grow better.

Antibiotic pressure selects for bacteria that have heightened mutation rate. This increased mutation rate is typically conferred by alterations in genes that constitute the mismatch repair system (MMR) (mutS, mutL, mutH, mutT, mutY, mutM, and uvrD).

Mutations in the MMR system also increases the prevalence of genetic recombination, providing diversity to antibiotic resistance mechanisms.

Methods for dissemination of antimicrobial resistance genes

1) Conjugation (bacteria-to-bacteria transfer)

2) Transduction (viral-mediated transfer)

3) Transformation (free DNA transfer)

Conjugation

Transfer of DNA between two bacterial cells connected by sex pili

Transduction

Transfer of bacterial DNA between a bacteriophage-infected bacterium and a bacteriophage-susceptible bacterium

Bacteriophage acts as conduit for shuttling bacteria genes from one cell to another, thus negating the necessity for cell-to-cell contact

Transformation

New genes acquired directly from environment. Natural incorporation of naked DNA to develop resistance.

Process requires donor cell which lyses and releases naked DNA into environment.

The recipient cell is one that is capable of taking up the DNA from the environment and incorporating it into its genome.

HOW?

1) Random pieces of DNA bind to receptors on outside of bacterium and are transported into the cell via DNA translocase. Once inside the cell, DNA is incorporated into bacterial chromosome via RecA for genes to be expressed.

Jumping genes

Transposable elements can be responsible for activation or inactivation of genes in an organism.

Transposable elements move from one location to the next within DNA molecule via transposition, faciliated by enzyme transposase.

1) Conservative transposition = transposon removed from one location and relocated to another

2) Replicate transposition = transposon can be copied, with the copy being inserted at a second site.

Antibiotics that inhibit cell wall biosynthesis

Beta-lactams

Glycopeptides

Antibiotics that inhibit folate biosynthesis

Trimethoprim

Suphonamides

Antibiotics that inhibit protein synthesis

Aminoglycosides

Tetracyclines

Macrolides

Antibiotics that inhibit transcription

Rifamycin

Antibiotics that inhibit DNA synthesis

Fluoroquinolones

Multiple drug resistance (MDR)

The ability of microbes to show resistance against three or more categories of antibiotics

Different bacteria have shown multiple drug resistance (MDR).

Give some examples of these bacteria...

Staphylococcous aureus

Clostridium difficile

Klebsiella pneumonia

Streptococcus pneumoniae

Mycobacterium tuberculosis

Salmonella enterica

Main distinctive features of S. aureus

- Production of extracellular enzyme coagulase, which converts fibrinogen into fibrin

- Production of thermostable nucleases that breaks down DNA

- Production of surface-associated protein known as clumping factor or bound coagulase that reacts with fibrinogen

S. aureus

Gram positive cocci arranged in grape-like clusters

Methicillin resistance in staphylococci is due to the acquisition of ___ ___ element, called the staphylococcal ___ ___ ___.

Methicillin resistance in staphylococci is due to the acquisition of mobile genetic element (MGE) called the staphylococcal cassette chromosome mec (SCCmec).

All SCCmec types include the ___ gene, which codes for low-affinity penicillin-binding protein PBP-2a as a factor necessary for methicillin resistance.

All SCCmec types include the mecA gene, which codes for low-affinity penicillin-binding protein PBP-2a as a factor necessary for methicillin resistance.

SCCmec elements also include ccr genes = for integration & excision from the chromosome.

The strains of S. aureus that have acquired what gene - are designated as MRSA?

mecA gene (which encodes for novel penicillin-binding protein, PBP-2a) are designed as methicillin-resistant S. aureus (MRSA)

Infections caused by MRSA

- Skin & soft tissue, bone & joint infection

- Medical device related infection

- Pneumonia

- Bloodstream infection

- Infective endocarditis

- Aortic root abscess

- Discitis

- Spinal epidural abscess

- Toxic shock syndrome

- Necrotising fasciitis

MRSA strains are resistant to...

All beta-lactam antibiotics and often to other agents as well (e.g., aminoglycosides, fluoroquinolones)

Agents of choice in treating systemic MRSA infection

Glycopeptides e.g., vancomycin or teicoplanin

Some rare isolates of MRSA have been found to have reduced susceptibility or full resistance to glycopeptide antibiotics.

What types of adaptations do these MRSA isolates have?

1) Reduced susceptibility = thickened cell walls

2) Fully resistant = vanA gene presence

Treatment of severe infections caused by S. aureus should be started with what antibiotic?

Flucloxacillin

*unless MRSA is endemic locally, in which case - glycopeptide such as Vancomycin is indicated

If a patient with MRSA is allergic to penicillin, what should be given?

Erythromycin

Clindamycin

Vancomycin

Consequence of antimicrobial resistance

- Increase in morbidity & mortality

- Hospitalisation prolonged or patient may be isolated

- Drugs more toxic or expensive

WHO five strategic objectives for decreasing antimicrobial resistance

1) Improve awareness/education on antimicrobial resistance

2) Strengthen knowledge via surveillance/research

3) Reduce incidence of infection

4) Optimise use of antimicrobial agents

5) Develop economic case for sustainable investment that takes into account of needs of all countries, and increase investments in new medicines, diagnostic tools, vaccines & other interventions

What term is used to describe the ability of microbes to endure the selective pressures of their environment?

a) Antimicrobial resistance

b) Therapeutic index

c) Microbial adaptation

d) Clonal expansion

e) Free DNA acquisition

Microbial adaptation

Difference between antibiotic and antimicrobial resistance

Antibiotic resistance refers to resistance in bacteria, while antimicrobial resistance includes resistance of microorganisms to any type of drug used for infection treatment.

What is meant by co-resistance?

Resistance to multiple classes of antibiotics in the same bacterial strain

Which term describes a single resistance mechanism conferring resistance to an entire class of antibiotics?

Cross-resistance

Which antibiotic is commonly used to treat Methicillin-Resistant Staphylococcus aureus (MRSA) infections?

a) Amoxicillin

b) Gentamicin

c) Vancomycin

d) Ciprofloxacin

e) Penicillin

c) Vancomycin

What is the main mode of transmission for MRSA infections?

a) Airborne

b) Waterborne

c) Vector-borne

d) Person-to-person contact

e) Foodborne

d) Person-to-person contact

Which of the following infections is commonly caused by MRSA?

a) UTIs

b) Sinus infections

c) Skin and soft tissue infection

d) Pneumonia

e) Gastrointestinal infection

c) Skin and soft tissue infection

Which gene confers resistance to all beta-lactam antibiotics in MRSA?

a) vanA gene

b) penA gene

c) mecA gene

d) tetM gene

e) gyrA gene

c) mecA gene