Microbiology 2500: Antibiotics & Resistance

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Questions and Answers

What is the primary mechanism by which horizontal gene transfer contributes to antibiotic resistance in bacteria?

Increased efflux of antibiotics from bacterial cells

Acquisition of new genes from other bacteria (correct)

Inhibition of antibiotic target sites

Mutations within the bacterial chromosome

Which of the following is classified as a serious antibiotic-resistant threat according to the CDC?

Vancomycin-resistant Staphylococcus aureus (VRSA)

Erythromycin-resistant Group A Streptococcus

Carbapenem-resistant Enterobacteriaceae (CRE) (correct)

Drug-resistant Neisseria gonorrhoeae

What type of bacteria is known to produce New Delhi Metallo-beta-lactamase-1 (NDM-1)?

Aerobic bacteria

Gram-negative rods (correct)

Gram-positive cocci

Spore-forming bacteria

Which antibiotic is primarily resistant due to the activity of β-lactamases?

Penicillin Signup and view all the answers

What is the characteristic feature of Clostridia bacteria?

They are strict anaerobes and produce exotoxins Signup and view all the answers

What role does the capsule produced by Klebsiella pneumoniae play in its pathogenicity?

It prevents phagocytosis by immune cells Signup and view all the answers

What is a significant public health challenge posed by vancomycin-resistant enterococci (VRE)?

They are resistant to multiple antibiotics, limiting treatment options Signup and view all the answers

Which bacterium is known for causing pseudomembranous colitis?

Clostridioides difficile Signup and view all the answers

What is the primary risk factor for developing pseudomembranous colitis?

Recent antimicrobial use Signup and view all the answers

Which of the following symptoms is NOT associated with pseudomembranous colitis?

Skin rash Signup and view all the answers

How do the A-B toxins produced by C. difficile affect host cells?

Inactivate key regulatory proteins Signup and view all the answers

What is the primary mode of transmission of C. difficile?

Fecal-oral route Signup and view all the answers

Which of the following antibiotics is specifically recommended for treating C. difficile infections?

Oral vancomycin Signup and view all the answers

What is a significant complication of the C. difficile endospores in hospital settings?

Difficulty in eradicating the spores from the environment Signup and view all the answers

Which condition occurs when normal microbiota is suppressed and allows C. difficile to overgrow?

Antibiotic-associated diarrhea Signup and view all the answers

Endoscopy can show characteristic lesions associated with which condition?

Pseudomembranous colitis Signup and view all the answers

What is a primary mechanism through which antibiotic resistance occurs in bacteria?

Horizontal gene transfer among bacteria Signup and view all the answers

Which of the following is a common result of using broad-spectrum antibiotics?

Development of antibiotic-resistant strains Signup and view all the answers

What is the primary target of β Lactam antibiotics in bacterial cells?

Cell wall synthesis Signup and view all the answers

What is a major concern regarding the use of Vancomycin?

Its efficacy is declining due to resistance development. Signup and view all the answers

Which of the following statements accurately describes antibiotics in animal feeds?

They contribute to the development of antibiotic resistance. Signup and view all the answers

Which of the following is identified as one of the CDC's antibiotic-resistant threats?

All of the above Signup and view all the answers

What role does the minimum inhibitory concentration (MIC) play in evaluating antibiotics?

It determines the lowest concentration of an antibiotic that inhibits bacterial growth. Signup and view all the answers

Which of the following best describes the misuse of antibiotics in pediatric patients?

Using antibiotics to treat viral infections. Signup and view all the answers

Study Notes

Western University

Founded in 1878
Located in Canada

Microbiology and Immunology 2500: Antibiotics and Antibiotic Resistance

Course taught by Dr. Idowu Olawoye
Course objective is to understand how antibiotics work and antibiotic resistance; recognize major bacterial pathogens; and describe how antibiotic use leads to pseudomembranous colitis

Antimicrobial Agents

Disinfectants: antimicrobial agents applied to inanimate objects (e.g., floors, tables, walls)
Antiseptics: antimicrobial agents safe for use on living tissues (e.g., hand sanitizer)
Antibiotics: antimicrobial agents produced by bacteria and fungi, used by humans topically and internally

Antibiotics

Very effective against bacterial infections
Essential for cancer chemotherapy, organ transplantation, surgeries, and premature infants treatments
Pharmaceuticals have decreased interest in developing new antibiotics.
Bacterial resistance to antibiotics is consistent.

Antimicrobial Deployment and Resistance

Graph showing the deployment and observation of antibiotic resistance over time for various antibiotics.

Misuse of Antibiotics

Empiric (blinded) use: indiscriminate prescription without proper diagnosis.
Increased us of broad-spectrum agents: overuse of antibiotics effective against many pathogens, often for viral infections.
Incomplete course use: patients not completing the full antibiotic regimen leading to antibiotic-resistant bacteria.
Antibiotics in animal feeds: use of antibiotics to promote animal growth which contributes to antibiotic resistance in bacteria.

Measuring Antibiotic Activity

Minimum inhibitory concentration (MIC): determination of the lowest antibiotic concentration that stops bacterial growth.
Methods include culture tubes with varying antibiotic concentrations, and antibiotic strips for high-throughput analysis.

How Antibiotics Work

Essential bacterial targets: cell wall synthesis, protein synthesis, DNA/RNA synthesis, folate synthesis, and cell membrane alteration.
Targets are absent or different in eukaryotic cells.

β-Lactam Antibiotics

Example: Penicillin
Contain a beta-lactam ring
Inhibit cell wall synthesis in bacteria
Bind to bacterial penicillin-binding proteins (PBPs) -- transpeptidases.
No peptide cross-links result in cell death.
Some bacteria produce beta-lactamases to destroy the ring and antibiotic.
Example: Methicillin
Chemically modified penicillin
Not cleaved by beta-lactamases
Some bacteria produce a different penicillin-binding protein (e.g., PBP2a). PBP2a doesn't bind to methicillin.

Vancomycin

Glycopeptide antibiotic
Inhibits cell wall synthesis in Gram-positive bacteria.
Often drug of last resort for Gram-positive infections.
Binds to D-ala-D-ala residues.
Resistance results from changing D-ala-D-ala to D-ala-D-lac, preventing vancomycin binding.
Resistance encoded by van genes.

Selection for Antibiotic Resistance

Use of antibiotics selects for antibiotic-resistant bacteria.
Susceptible bacteria are eliminated, leaving behind resistant bacteria that multiply.

Bacterial Strategies for Antibiotic Resistance

Prevention of antibiotic entry: Gram-negative outer membrane; mycobacterial cell envelope.
Antibiotic modification: β-lactamase, which inactivates some antibiotics.
Efflux of antibiotic: actively pumping out antibiotic to limit or prevent its effect.
Alteration of antibiotic target: modifications to PBPs or ribosomes.
Bypassing antibiotic action: using alternative source or methods to carry out function.

Antibiotic Resistance Genes

Many resistance mechanisms are genetically encoded (e.g., mec, β-lactamase, efflux pumps).
Often encoded on mobile genetic elements (plasmids) that allow for horizontal gene transfer between bacteria, leading to "superbugs."

Horizontal Gene Transfer

Transfer of genes rather than mutations (altering functions).
Genes acquired from another source.
Three mechanisms: transformation, transduction, and conjugation.

CDC Biggest Antibiotic-Resistant Threats

Serious threats: Drug-resistant Campylobacter, Multidrug-resistant Acinetobacter, Fluconazole-resistant Candida, Extended-spectrum Beta-lactamase producing Enterobacteriaceae, Vancomycin-resistant Enterococcus (VRE), Multidrug-resistant Pseudomonas aeruginosa, Drug-resistant non-typhoidal Salmonella, Drug-resistant Salmonella Serotype Typhi, Drug-resistant Shigella, Methicillin-resistant Staphylococcus aureus (MRSA), Drug-resistant Streptococcus pneumoniae, Drug-resistant Tuberculosis
Urgent threats: Clostridioides difficile, Carbapenem-resistant Enterobacteriaceae (CRE), Drug-resistant Neisseria gonorrhoeae
Concerning Threats: Vancomycin-resistant Staphylococcus aureus (VRSA), Erythromycin-Resistant Group A Streptococcus, Clindamycin-resistant Group B Streptococcus

Klebsiella pneumoniae

Gram-negative bacterium.
Important cause of nosocomial pneumonia.
Commonly resistant to multiple antibiotics.
First documented source of NDM-1 (New Delhi Metallo-β-lactamase-1). NDM-1 is a carbapenemase, and the resistant form is CRE (carbapenem-resistant Enterobacteriaceae).

Clostridia

Gram-positive, rod-shaped, endospore-forming bacteria.
Strict anaerobes (killed by oxygen).
Found in soil and animal intestinal tracts.
Important human pathogens: Clostridioides difficile, Clostridium tetani, Clostridium botulinum, Clostridium perfringens (causes life-threatening diseases through exotoxins).

Clostridioides difficile

Can exist as an asymptomatic carrier in the large intestine.
Capable of causing mild to severe diarrhea and life-threatening pseudomembranous colitis.
Found in nursing homes, and hospital environments.
Difficult to eradicate due to endospores.
Mode of transmission is spore-based fecal oral route.
Causes pseudomembranous colitis.
Antibiotic-associated diarrheal complication.

Pseudomembranous Colitis

Inflammatory condition of the large intestine.
Triggered by the use of antimicrobial agents.
Characterized by diarrhea, abdominal pain, fever, nausea, and dehydration.

Clostridioides difficile Toxins

C. difficile produces A-B toxins (large clostridial cytotoxins).
A-domain is the active component of the toxin.
B-domain helps bind to the host cell and activates the toxin entry.
A-toxin inactivates key regulatory proteins which cause dysregulation of multiple cell processes leading to cell death and inflammation.

Diagnosis and Treatment of C. difficile

History of antibiotic use and symptoms.
Laboratory testing and endoscopic evaluation to confirm.
Discontinuation of triggering antibiotic use.
Treatment with fluids, and more specific antibiotics (oral vancomycin or IV metronidazole).
Antidiarrheal drugs should be avoided, as they may reduce toxin clearance.

Fecal Microbiota Transplantation

Procedure utilizes donor stool to restore the normal gut bacteria for individuals with C. difficile infections.
Method of fecal transplantation, through nasoduodenal or nasogastric infusion.

Fecal Microbiota Transplantation Studies

Study demonstrated that this restoration of intestinal microbiota effectively cures C. difficile infections.

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Description

Explore the key concepts of antibiotics and antibiotic resistance through this quiz based on the Microbiology and Immunology 2500 course. Understand how antibacterial agents work, recognize major bacterial pathogens, and learn about the implications of antibiotic use. Enhance your knowledge on disinfectants, antiseptics, and the impact of bacterial resistance.