HLSC Class 5 Part 1

What is the biological definition of antibiotic resistance?

The expression of a gene mutation in a bacterium that permits it to proliferate in the presence of an antibiotic designed to kill it.

What is the primary clinical consequence of increasing antimicrobial resistance in pathogens?

Commonly used antimicrobials become ineffective against the diseases caused by those microorganisms.

How does increasing antibiotic resistance impact bacterial virulence and patient hospitalization?

Bacteria become more virulent, requiring stronger antibiotics or hospitalization due to severe complications from previously simple infections.

In addition to random natural mutation, how can antibiotic resistance be artificially engineered?

By applying an evolutionary stress on a population.

By what mechanism do bacteria horizontally transfer resistance genes between individuals?

Plasmid exchange

What term is used to describe a bacterium that carries multiple resistance genes?

Multiresistant bacterium (or superbug)

What is the mechanism of action of $\beta$-lactam antibiotics?

Interfering with bacterial cell wall synthesis

Which major antibiotic classes belong to the $\beta$-lactams?

Penicillins, Carbapenems, Cephalosporins, and Monobactams

Which non-$\beta$-lactam glycopeptide antibiotic acts by inhibiting cell wall synthesis?

Vancomycin

What ribosomal subunits do protein synthesis inhibitor antibiotics target?

The $30\text{S}$ subunit and the $50\text{S}$ subunit

Which classes of antibiotics specifically target the bacterial $30\text{S}$ ribosomal subunit?

Tetracyclines and Aminoglycosides

Which classes of antibiotics target the bacterial $50\text{S}$ ribosomal subunit?

Macrolides, Clindamycin, Linezolid, Chloramphenicol, and Streptogramins

What enzyme do Quinolones target to inhibit bacterial DNA replication?

DNA Gyrase

What enzyme does Rifampin target to inhibit bacterial nucleic acid synthesis?

RNA Polymerase

How do antimetabolite antibiotics like Sulfonamides and Trimethoprim kill bacteria?

They prevent the bacterial synthesis of folate.

Which bacterial precursor is blocked at the beginning of the folate synthesis pathway by Sulfonamides?

Para-aminobenzoic acid (PABA)

Which Institut Pasteur scientist recorded the antibiotic effect of Penicillium in 1923?

Clodomiro Picado

Who discovered penicillin in 1928 after observing a halo of bacterial growth inhibition around mold?

Sir Alexander Fleming

What specific mould species did Alexander Fleming isolate to produce penicillin?

Penicillium notatum

What primary warning did Alexander Fleming issue regarding the improper use of penicillin?

Thoughtless overuse or under-dosing leads to the selection and spread of penicillin-resistant organisms.

What are the three main mechanisms bacteria utilize to prevent entry of antibiotics?

Porin system modifications, formation of biofilms, and development of efflux pumps.

How do bacteria alter target sites to evade antibiotic action?

By creating a blockade around the target or changing the amino acid sequence of the targeted protein.

How do bacteria directly modify or destroy antibiotic molecules?

By producing enzymes that destroy the drug (e.g., $\beta$-lactamases) or by binding interfering molecules to it.

What does MRSA stand for?

Methicillin-resistant Staphylococcus aureus

What percentage of MRSA infections occur in individuals with no recent hospital contact?

7%

What severe systemic complications can arise from MRSA infection beyond skin lesions?

Pneumonia, endocarditis, bacteremia, and osteomyelitis

Which two species of Enterococcus are the primary causes of VRE infections?

Enterococcus faecium and Enterococcus faecalis

What is the clinical distinction between VRE colonization and active VRE infection?

Colonization means bacteria are present without symptoms; infection involves active disease in sites like the urinary tract or bloodstream.

What does CRE stand for in clinical microbiology?

Carbapenem-resistant Enterobacteriaceae

What enzyme is produced by CRE organisms to resist antibiotic treatment?

Carbapenemase (an enzyme that neutralizes carbapenem antibiotics)

Why is resistance to carbapenems in Enterobacteriaceae particularly dangerous?

Carbapenems are considered drugs of last resort for severe bacterial infections.

What defines Multidrug-Resistant Tuberculosis (MDR-TB)?

Resistance of Mycobacterium tuberculosis to at least the two key first-line drugs: Rifampin and Isoniazid.

What are the four standard first-line drugs used for drug-sensitive Tuberculosis?

Isoniazid, Rifampin, Ethambutol, and Pyrazinamide

What defines Extensively Drug-Resistant Tuberculosis (XDR-TB)?

TB resistant to first-line drugs (Rifampin and Isoniazid) plus second-line treatments including fluoroquinolones and injectable second-line agents.

Which newly introduced drugs are utilized in the management of resistant TB strains?

Bedaquiline and Delamanid

What major internal human anatomical site serves as a primary reservoir for antibiotic resistance genes?

The human gut microbiota

Why does untreated hospital wastewater present a high environmental risk for antibiotic resistance?

It contains $\mu\text{g/L}$ levels of antibiotic residues alongside highly abundant resistant pathogens and mobile resistance genes.

What is bioterrorism?

The intentional release or dissemination of biological agents (naturally occurring or human-modified bacteria, viruses, or toxins) into a population.

In 1346, what biowarfare tactic was used during the siege of Caffa on the Crimean Peninsula?

Tartars catapulted the bodies of plague victims over the city walls.

What biological agent was weaponized via contaminated blankets distributed to Native Americans in 1763?

Smallpox virus

What key criteria define a Category A bioterrorism agent?

Easy dissemination, high mortality rate, high potential for social disruption/panic, and major public health impact requiring emergency preparedness.

Which biological threats are classified as Category A bioterrorism agents?

Anthrax, Botulism, Plague, Smallpox, Tularemia, and Viral Hemorrhagic Fevers

What is the causative bacterial organism of anthrax?

Bacillus anthracis

What form does Bacillus anthracis take to persist in soil for decades?

Dormant spores

What physical processing step is required to weaponize anthrax spores for aerosol dissemination?

Fine milling of spores to ensure they remain airborne and promote inhalation.

What are the five clinical forms/routes of Anthrax infection?

Cutaneous, Inhalation, Gastrointestinal, Meningitis, and Injection (e.g., in heroin users).

What is the typical clinical course and timeline of fatal inhaled anthrax?

Spores cause pneumonia with hemorrhages and blood vessel breakdown; death typically follows within 5 days.

What pathological effects occur following ingested anthrax infection?

Stomach and intestinal ulcers, gangrene of the spleen, and fatality within 3 days.

What full organization name corresponds to CARSS in Canadian public health?

Canadian Antimicrobial Resistance Surveillance System

What is the primary objective of CARSS?

To synthesize epidemiological and laboratory data across humans, food, and animals to guide policies controlling antimicrobial resistance in Canada.

What international body does Canada collaborate with to improve response to chemical, biological, and radio-nuclear terrorism?

The Global Health Security Action Group (GHSAG)

What are the 10 main classes of antibiotics

1. beta-lactams - penicillins, carbapenems, cephalosporins

2. sulfonamides

3. quinolones

4. tetracyclines

5. macrolides

6. aminoglycosides

7. vancomycin

8. rifampin

(for some reason there aren’t 10 in the slideshow)

Name and explain the 3 ways of developing antibiotic resistance

1. Prevent antibiotic entry - modifications to the bacterial porin system, biofilms, or by developing efflux pumps antibiotics do not have sufficient access to the cell to be therapeutic

2. Modify the antibiotic’s target site - bacteria can create a blockade around the antibiotic’s target, or change the amino acid sequence of the protein being targeted, reducing the antibiotic’s affinity

3. Modify the antibiotic itself - destroy the antibiotic (beta-lactamases), or bind a molecule to the antibiotic that interferes with its function

__ million people in the US contract drug-resistant bacterial infections each year

Mortality = ___ deaths per year

• 2

• 23,000

Mortality rates from Anthrax

cutaneous =

GI =

inhalation =

• 20%

• 25%-75%

• greater than or equal to 80%