(Section C: Bacteriology) Lecture 20 Flashcards by Lucky Cat

What are the 3 classifications of antimicrobial agents?

Disinfectants
Antiseptics
Antibiotics

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Disinfectants

Antimicrobial agents that are applied to inanimate objects
* Floors, tables, walls etc.

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Antiseptics

Antimicrobial agents that are sufficiently nontoxic to be applied to living tissues
* E.g. Hand sanitizers

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Antibiotics

Antimicrobial agents produced by bacteria and fungi that are exploited by humans

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How are antibiotics delivered/administered?

Topically
Internally

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What are 2 major problems with antibiotics?

Diminished interest from pharmaceutical companies to develop new antibiotics
Bacterial resistance to antibiotics always happens

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What are 5 examples of misuse of antibiotics?

Empiric/blinded use
Increased use of broad-spectrum agents
Pediatric use for viral infections
Patients who do not complete course of treatment
Antibiotics in animal feeds

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Blinded use

Using random antibiotics for diseases

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Increased use of broad-spectrum agents

Antibiotic that is effective against wide variety of bacteria
* Causes large-scale development of resistance

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Pediatric use for viral infections

Misuse, not useful for viral infections and may cause resistance to develop by bacteria

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Patients who do not complete course of treatment

E.g. Tuberculosis
* Treatment usually lasts 6 months or more
* Bacteria may develop resistance if the treatment is not carried through all the way

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Antibiotics in animal feeds

Spreads to environment through defecation
* Causes bacteria in the environment to gain resistance

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How is antibiotic activity measured?

Minimum inhibitory concentration (MIC)

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What is the MIC defined as?

The lowest concentration of agent that inhibits growth completely

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How is MIC conducted (traditionally)?

Series of culture tubes with varying concentration of antibiotic
* MIC is the lowest concentration where there is no growth of bacteria

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How is MIC conducted (modern)?

Antibiotic strips
* Faster to do
* Can test multiple antibiotics at the same time

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How do antibiotics work?

Target essential bacterial components

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What components do antibiotics target?

Cell wall synthesis
Protein synthesis
DNA/RNA synthesis
Folate Synthesis
Cell membrane alteration

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How do antibiotics ensure they target bacterial cells?

Targets are either
* Not present in eukaryotic cells
* Different in eukaryotic cells

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β Lactam Antibodies
* Example
* Structure
* Function

* Penicillin, Methicillin
* Contain a "β Lactam ring"
* Function to inhibit cell wall synthesis in bacteria

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How do β Lactam antibiotics work to inhibit cell wall synthesis?

Bind to bacterial “penicillin-binding proteins” (PBPs)
PBPs are transpeptidases
No peptide cross links = Weak cell wall = Cell death

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How do bacteria counter β Lactam Antibiotics?

(Unmodified, use penicillin as example)

Produce β Lactamase
* Enzyme that destroys the β Lactam ring

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How is methicillin different from penicillin?

Chemically modified penicillin
Cannot be cleaved by β lactamases

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How do bacteria counter β Lactam Antibiotics?

(Modified, use methicillin as example)

Produce a different “penicillin-binding protein” (PBP)
* Called PBP2a or ‘mec’
* Doesn’t bind to methicillin or other β lactams

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Vancomycin * Type of antibiotic * Function

* Glycopeptide antibiotic * Inhibits cell wall synthesis in Gram positives

# True or False: Vancomycin is used last in a treatment

True, it is a drug of "last resort"

How does Vancomycin work?

Binds the peptide linkage at terminal D-Ala-D-Ala residues * Inhibits transpeptidation, weakens cell walls

How do bacteria counter Vancomycin?

Changes terminal to D-Ala-D-Lac * Vancomycin can no longer bind * Encoded by 'van' genes

What are methods that bacteria use for antibiotic resistance?

1. Prevention of antibiotic entry 2. Antibiotic modification 3. Efflux of antibiotic 4. Alteration of antibiotic target 5. Bypassing the antibiotic action

# Examples: Prevention of antibiotic entry

* Gram negative outer membrane * Mycobacteria cell envelope

# Examples: Antibiotic modification

β lactamase

# Definition: Efflux of antibiotic

Actively pumping out the antibiotic

# Examples: Alteration of antibiotic targett

* PBPs * Ribosome modifications

# Examples: Bypassing the antibiotic action

Using environmental folic acid

# True or False: Many mechanisms of antibiotic resistance are genetically encoded

True

Where are antibiotic resistance mechanisms encoded on?

Mobile genetic elements (plasmids) * Allows for horizontal gene transfer

What can horizontal gene transfer create?

Superbugs

What is horizontal gene transfer?

New genes are acquired from another source * Not acquired through gene mutations

What are forms of horizontal gene transfer? Explain each

1. **Bacterial transformation**: Cell lysis releases genes to other cells 2. **Bacterial transduction**: Virus picks up gene and implants in another cell 3. **Bacterial conjugation**: Gene directly transferred to another cell when they join

Klebsiella pneumoniae * Type * Disease it causes * Antibiotic

* Gram negative * Causes nosocomial pneumonia * Carbapenem antibiotics

What are carbapenem antibiotics?

β lactamse resistant β-lactams with broad spectrum activity

What does Klebsiella pneumoniae do in its life cycle?

Produces a capsule

How is Klebsiella penumoniae resistant to carbapenem?

"NDM-1" enzyme * Known as carbapenemase

# True or False: NDM-1 is only present in Klebsiella pneumoniae

False, it is now widespread in other Gram negatives too (e.x. CRE - carbapenem resistant Entrobacteriaceae)

Clostridia * Type * Shape * Characteristics

* Gram positive * Rod shaped * Endospore formers, strict anaerobes

Where is Clostridia generally found?

* Soil * Intestinal tracts of animals

# List: Important human pathogens in Clostridia

* *Clostridiodes difficile* (pseudomembraneous colitis) * *Clostridium tetani* (tetanus) * *Clostridium botulinum* (botulism) * *Clostridium perfringens* (food-borne illness, gas gangrene)

How do Clostridia cause life threatening disease?

Exotoxins

How can Clostridioides difficile exist as?

* Asymptomatic carrier state in the large intestine * Cause of mild/moderate diarrhea * Cause of life-threatening pseudomembranous colitis

What type of pathogen is C. difficile? Where is it often found?

A nosocomial pathogen * Nursing homes, hospital environments

Why is C. difficile so difficult to eradicate?

Endospores are difficult to eradicate * Cultured from floor, bed pans, toilets, hands, and clothing of medical personnel

Mode of transmission of C. difficile

Fecal-oral route

What condition can C. difficile cause?

Pseudomembraneous colitis (aka Antibiotic-associated diarrhea)

What is pseudomembraneous colitis?

Inflammatory condition of the large intestine * Risks: Recently received an antimicrobial agent

Signs/symptoms of pseudomembranous colitis

* Diarrhea * Abdominal pain * Fever * Nausea * Dehydration

How long does it take for signs/symptoms of pseudomembranous colitis to show?

May occur * 1-2 days after antibiotics * Several weeks after the antibiotic is discontinued

What do endoscopy in pseudomembranous colitis patients show?

Characteristic lesions * Enlarge to cover substantial portions of inflamed mucosa * Can be stripped off

What is the etiology behind pseudomembranous colitis?

Antibiotics cure infections, but also kill normal microbiota * Suppression of normal microbiota + Persistence of C. difficile endospores = Pseudomembraneous colitis

Is C. difficile considered an invasive bacterium?

No * Exotoxins cause damage and inflammation to the intestinal lining of the large intestine

What toxins do C. difficile produce?

A-B toxins known as "Large clostidial cytotoxins"

What does the "A-B" stand for in A-B toxins?

* A domain: Active portion of the toxin that carries the enzymatic activity * B domain: Binding portion, responsible for binding and uptake by the host cells

How does the A domain work in large clostridial cytotoxins?

Inactivates key regulatory proteins of host cells * Causes dysregulation of multiple cell processes including cytoskeletal rearrangements, cell death and inflammation

How is pseudomembraneous colitis diagnosed?

* History: Antibiotic use * Symptoms * Laboratory tests: C. difficile * Endoscopy * Toxin detection assays

What is the treatment for pseudomembranous colitis?

* Discontinue antibiotic * Fluids * Use antibiotics specific for C. difficile (oral vancomycin or I.V. metronidazole)

Why should antidiarrheal agents be avoided in pseudomembranous colitis?

Would cause decreased toxin clearance

What is a new treatment method for pseudomembranous colitis?

Fecal microbiota transplantation

What is fecal microbiota transplantation? Why is it used?

Literally taking fecal matter from healthy patient and implanting into patients with pseudomembranous colitis * Builds the microbiota lost to antibiotic use