Pharmaceutical Microbiology Quiz

Microbial Communities & Antimicrobial Resistance

• The presentation discusses microbial communities and antimicrobial resistance.
• A figure shows a diagram of bacterial structure emphasizing the genetic material (chromosome and plasmids).
• The chromosome is double-stranded DNA, circular, and larger than 1200 μm when folded.
• Plasmids are extrachromosomal DNA fragments, typically circular, and non-essential for bacterial survival.
• The presentation also describes external bacterial structures like pili/fimbria for adherence, capsule for protection against phagocytes and antibiotics, and flagellum for movement.
• The gut microbiome is described as a highly diverse ecosystem with 100 billion inhabitants and ~1000-2000 species.
• Its composition is unique.

Bacterial Structure (1)

• Bacteria have a capsule, cell wall, plasma membrane, cytoplasm, ribosomes, plasmids, and pili.
• Bacterial flagellum and nucleoid (circular DNA) are also components.

Bacterial Structure (2)

• Pili/Fimbria: protein-based structures facilitating bacterial adherence and conjugation.
• Capsule: sugar-based outer layer, shielding bacteria from phagocytosis and antibiotics
• Flagellum: protein structure enabling bacterial motility.

The Gut Microbiome

• The gut microbiome is a highly diverse ecosystem.
• It contains 100 billion inhabitants and 1000-2000 species of microbes.
• Its composition is unique.

Trivia about our Microbiome

• Gut microbiota contributes to body weight.
• Microbes in the human body consume nutrients.
• Microbes generate gas from metabolism.

Microorganisms as Symbionts

• Microorganisms function as symbionts through co-evolution and co-adaptation.
• Bacteria (Bacteroides plebeis) break down polysaccharides from nori (Porphyra spp.).
• Carbohydrate-degrading enzymes are transferred from marine bacteria to Japanese human populations.

How Bacteria Talk

• The presentation mentions bacteria communication via quorum sensing mechanisms.
• The presentation emphasizes the bobtail squid and its symbiotic relationship with Vibrio fischeri bacteria.

Counter-illumination

• The presentation discusses the counter-illumination technique.

Bacterial Communication (Quorum Sensing)

• Quorum sensing is bacterial communication.
• This process controls various bacterial behaviors.

Important Functions of Microbes

• Microbes are important within the human body, food processing, and natural environments.

Functions of the "Forgotten Organ"

• The gut microbiome produces vitamins (B12, K, and folate)
• It assists the immune system by differentiating friend or foe cells.
• It defends against harmful microorganisms.
• It regulates caloric intake.
• The gut bacteria produce serotonin vital for optimal gut function.

Ecosystem Perturbations & Westernization

• The presentation addresses ecosystem perturbations and westernization.
• It features a book cover highlighting the topic of "Missing Microbes."

Dysbiosis of "The Forgotten Organ"

• Dysbiosis of the gut microbiome has effects on the body.
• The presentation highlights the relationship between dysbiosis and other bodily functions such as anxiety, depression, diabetes, etc.

Microbiome Resistome

• The presentation defines microbial biome and resistome.
• The resistome is a reservoir for antimicrobial resistance (AMR) bacteria.
• The presentation links the microbiome's complexity and diversity to exposure to AMR bacteria.
• The presentation links increase in AMR bacteria density through horizontal gene transfer (HGT).

Diseases Cause by Bacterial Infections

• The presentation asks a question about the diseases caused by bacterial infections.

Pathogenesis of Infections

• Pathogenesis involves disruptions in natural balance when host defenses are outweighed by the attack of invading microorganisms.

The Microorganism

• The presentation details the concept of a minimally infectious dose, which is the minimum number of microorganisms required for infection.
• Examples of minimally infectious cells include Vibrio cholera and Shigella.
• Primary pathogens differ from opportunistic pathogens.
• The routes of contamination are also presented.

Virulence

• Virulence is a pathogen's relative capacity to resist the host body's defenses.
• Adherence to host cells can be aided by bacterial pili.
• Direct damage may involve bacterial toxins.
• Invasion, a vital virulence trait, allows the pathogen to enter host cells.
• Immune system evasion enables pathogens to avoid detection or clearance by the immune system.

Virulence Factors

• Adhesion factors contribute to bacterial colonisation, local infection, and invasion.
• Bacterial fimbriae (adhesion factors) are crucial in adherence.
• Invasion factors facilitate bacterial invasion. Examples include type III/IV secretion systems.
• Capsules shield bacteria against phagocytosis (host cells).

Virulence Factors: Toxins

• The presentation discusses endotoxins, specifically lipopolysaccharide (LPS) a prototype endotoxin that triggers powerful host responses, cytokines production, fever and possible septic shock.
• Exotoxins, potent bacterial toxins, vary in structure. Some exotoxins consist of A and B subunits impacting host functions.  Examples include cytotoxins, neurotoxins, and enterotoxins.

Flagella, Urease and Bacteria Toxins

• Flagella and chemotaxis are vital for mucosal colonization.
• Urease neutralizes gastric acid via ammonia mechanism.
• Lipopolysaccharide (LPS) aids bacterial adherence.
• Outer proteins facilitate adherence to host cells.
• Exotoxins, like vacuolating toxin (vacA), inflict gastrointestinal harm. 
• Other toxins include mucinase, protease and lipase.
• The presentation describes how the type IV secretion system, a pilli like structure, helps to inject effectors(caga etc.) in host cells. Effectors cause actin remodeling, inflammation, host cell growth and apoptosis.

From Commensal to Pathogen

• Bacteria transition from commensal (normal) to pathogenic forms.

Antibiotics

• Antibiotics are substances produced by microorganisms that deter the growth of other microorganisms at high dilution.
• Antibiotics target different stages of bacterial growth.

1928: Alexander Fleming & Penicillin

• Alexander Fleming discovered penicillin in 1928.
• Penicillin aids infected soldiers as a life-saving antibiotic.

How do Antibiotics Work?

• Antibiotics distinguish between bacterial and eukaryotic cells and exploit these differences.
• Some interfere with bacterial replication, termed bacteriostatic. Also, some antibiotics kill bacteria directly, termed bactericidal.

Antibiotics: Mechanisms of Action

• Antibiotics operate through various mechanisms, including targeting cell wall synthesis, DNA replication, RNA synthesis, and protein synthesis. Examples include beta-lactams (for cell wall), quinolones (for DNA), and aminoglycosides/rifampin (for protein synthesis).

Broad- and Narrow-spectrum Antibiotics

• The presentation highlights the differences between broad-spectrum and narrow-spectrum antibiotics. 
• They differ regarding the spectrum of bacterial types they target.

Antibiotic Development

• Antibiotic development, including timeline and new classes of antibiotics discovery are highlighted.

Antibiotics Innovation Gap

• A presentation slide displays the antibiotic innovation gap between 1962 and 2000.
• The gap, a period lacking significant antibiotic classes, highlights the need for new treatments.

Reasons for Lack of New Antibiotics Development

• Pharmaceutical companies prioritize profit margins, which might not drive antibiotic development.
• Non-communicable diseases are more lucrative areas of research.
• Suppressive treatments for already diagnosed diseases or conditions are pursued over preventative strategies for infectious disease in patients.

Old & New Strategies

• Existing antibiotic designs are modified as an old strategy.
• New strategies search for new antibiotic sources in different environments (soil, aquatic).
• Novel drug design aims at interference with quorum sensing.

Quorum Sensing as Drug Target

• The presentation highlights quorum sensing as a drug target for controlling bacterial behaviors such as bioluminescence, sporulation, swarming, and secretion of virulence factors.

Antibiotic Resistance

• Antibiotic resistance poses a threat to global health.
• Surveillance programs allow for improved infection control mechanisms.

Antibiotic Resistance Worldwide & Europe

• Worldwide antibiotic resistance is increasing.
• The European Center for Disease Prevention and Control (ECDC) shows resistance patterns in Europe.

Global Rise in AMR Prevalence

• The presentation illustrates the global rise in antimicrobial resistance (AMR), particularly ESBLs (Extended-spectrum beta-lactamases).

Obama Acknowledged Drug-resistance

• President Obama recognized the problem of drug resistance.

Antibiotic Resistance in Perspective

• Deaths caused by antibiotic resistance are projected for the year 2050.
• Comparisons with other major causes of death (e.g., road accidents, cancer, etc.) emphasize the severity of this health crisis.

Antibiotic Deployment & Development of Resistance

• The antibiotic deployment chart illustrates the timeline of antibiotic discovery and antibiotic resistance timeline.
• It highlights antibiotics and the time period since a new antibiotic class was introduced.

Effect of Selective Antibiotic Pressure

• Selective antibiotic pressure promotes the development of antibiotic-resistant bacterial strains.
• Darwinian selection principles underpin this process.

Important Mechanisms for Resistance

• Bacterial resistance emerges via various mechanisms: enzymatic breakdown, decreased permeability to antibiotics, mutation in antibiotic targets, and active export through efflux pumps. 

Enzymatic Breakdown of Antibiotics (Beta-lactamases)

• Beta-lactamases break down penicillin by cleaving the beta-lactam ring, hindering antibiotic action.

Acquisition of Genetic Information by Bacteria

• Bacteria acquire genetic information via horizontal gene transfer such as transduction, transformation, and conjugation.

Mobile Genetic Elements

• Bacteria exchange genetic material via mobile genetic elements, particularly plasmids and phages.

Antibiotic Resistance in Perspective - Present

• Antibiotic use in humans and animals, as well as travel, contribute to the spread and emergence of resistance-associated genes, highlighted through different diagrams and charts about resistance levels and prevalence.

Important Mechanisms for Resistance

• Resistance to antibiotics develops via different mechanisms: antibiotic targets, and resistance mechanisms.

Multiresistant Bacteria

• Multiresistant bacteria are bacteria resistant to multiple antibiotics.
• The presentation lists examples of multiresistant bacteria, including vancomycin-resistant enterococci(VREs), and methicillin-resistant Staphylococcus aureus (MRSA).
• Extended-spectrum beta-lactamases (ESBL) producing gram-negative bacteria are also listed.

Beta-Lactamase

• The initial emergence of beta-lactamases against ampicillin is discussed.

Cephalosporins

• The development of 3rd generation cephalosporins in response to the wide-spread use of Beta-lactamase.

Extended-spectrum Beta-lactamases

• Extended-spectrum beta-lactamases (ESBLs) are enzymes that break down penicillins and cephalosporins.
• ESBLs arise through mutations and horizontal gene transfer.
• Carbapenems are last-resort treatment options.

ESBL: Mutations in Classical TEM and SHV Enzymes

• Mutations in TEM and SHV enzymes (types of beta-lactamases). allow bacteria to resist penicillins and cephalosporins.

ESBL: Acquisition Through HGT from Environmental Bacteria

• Horizontal gene transfer (HGT) is the movement of genes between bacteria (with and without antibiotic resistance).

Resistance in Europe

• Geographical data display resistance levels of third generation cephalosporins to Escherichia coli in Europe.

Carbapenemases

• Carbapenemases break down carbapenem antibiotics.
• The diagram depicts classes of antibiotics targeted and how carbapenem resistance arose.

Laboratory Diagnostics of Antibiotic Resistance

• Laboratory methods are used to detect antimicrobial resistance.

Antimicrobial Susceptibility: E-test & Disk Diffusion

• E-test and Disk diffusion methods are used to test the effectiveness of antibiotics.

Broth Microdilution Method

• Broth microdilution method is another test method to measure the minimal inhibitory concentration (MIC) of antibiotics for bacteria. The MIC is the lowest antibiotic concentration which prevents bacterial growth.

Cause of Emerging Antibiotic Resistance

• Factors that drive antibiotic resistance are explored.
• Research links the origin of resistance to specific factors (e.g., environment).

Effect of Selective Antibiotic Pressure

• Natural selection with antibiotic pressure drives the increase in resistance genes.

Where do Resistance Genes Come From?

• Resistance genes arise from spontaneous mutations and are present in environmental bacteria. 

Multiresistant Bacteria are a Threat

• The spread of multi-drug resistant bacteria causes a growing health crisis globally.

Conclusion

• A summary of critical issues in the presentation.
• An overall description of problems and solutions discussed is presented.