UF Bacterial Pathogens MCB4203 Exam 3

10. Inactivated toxin vaccines examples

inactivated forms of Corynebacterium diphtheria, Clostridium tetanus, and Bordetella pertussis toxins

-all inside the DTaP vaccine for protection against these diseases bc stimulate immune response w/o causing actual disease

Gene Transfer in Toxins - Main form

toxin genes can transfer, particularly horizontal gene transfer methods among bacterial strains

--can be done via plasmids, transposons, and bacteriophages as VEHICLES for gene transfer

Horizontal gene transfer

HGT is the process by which genetic material is transferred between organisms in a non-reproductive way, as opposed to vertical gene transfer (inheritance from parent to offspring). Plasmids are a major player in this process

10. Botulinum Neurotoxin in Medicine - uses+process

-Medical Uses: Treats muscle spasticity, chronic MIGRAINES, and is used cosmetically as Botox.

-Inhibits acetylcholine release at neuromuscular junctions, causing muscle relaxation

10. Antitoxins as Medical Interventions + Example

Neutralize toxins by binding to active sites

-Antitoxin for botulism is administered to prevent progression of paralysis

10. Antitoxin for botulism is administered to

administered to prevent progression of paralysis

10. Botulinum is a _ and is made by _

Neurotoxin produced by Clostridium botulinum

10. AB Toxins units

A-active subunit - subunit enters cell and disrupts cell processes

B-binding subunit - binds to HOST cell receptor

**10. AB toxin main example

diphtheria toxin inhibits protein synthesis of host by ADP-ribosylating elongation factor-2 EF2 (protein involved in translation) ((DP ADP EF)

10. Superantigens ... leads to ...

Bypass normal antigen presentation, causing massive T-cell activation and cytokine release, leading to TOXIC SHOCK (over-stimulation and inflammation)

10. Superantigen main example

Staph aureus causing Toxic shock syndrome toxin-1 (TSST-1)

10. Endotoxin main example

Lipopolysaccharide (LPS) in the outer membrane of gram-NEG bacteria.

10. LPS most harmful component

Lipid A triggers strong immune responses, leading to endotoxic shock

10. Endotoxin process

LIPIDS released out of bacteria after it undergoes LYSIS

10. Beta-Pore-Forming Toxin

secreted by bacteria to insert into host cell membranes, forming pores there that DISRUPT ION BALANCE ... host cell death

10. Gene Transfer Mechanism + Impact

Plasmids, transposons, and bacteriophages carry toxin genes

-Promote the spread of virulence factors (like toxin genes) among bacterial populations

10. Corynebacteriophage example

Diphtheria toxin gene is carried by bacteria virus called Corynebacteriophage that will enter many bacteria and spread this toxin gene to them ... DIP CORN

10. Bacillus thuringiensis (Bt) Toxins

-Biological insecticides targeting specific insect larvae.

-Toxins disrupt insect gut epithelial cells, leading to paralysis and death (Bt=beetle=insect=insectiside=kills larva by causing gut paralysis)

****10. Diphtheria Toxin from, impact, symptoms

from bacteria Corynebacterium diphtheriae.

-Inhibits host protein synthesis by ADP-ribosylation of elongation factor-2.

-Symptoms: Pseudomembranes in the throat, difficulty breathing (dipTHeriae for THroat issues)

10. Mycolactone Toxins

Produced by bacteria Mycobacterium ulcerans.

-Role: Causes tissue necrosis and immune SUPPRESION in a Buruli ulcer (no pain or inflammation in contrast to LPS causing septic shock w/ over-inflammation)

10. Botulinum Toxin

Produced by: Clostridium botulinum.

o Target: SNARE proteins in motor neurons bc TOXIN CLEAVES them to stop neurotransmitter release

o Effect: Blocks neurotransmitter release, leading to flaccid paralysis

10. Cholera Toxin

Produced by: Vibrio cholerae.

o Mechanism: Activates adenylate cyclase, increasing cAMP levels, causing massive water and electrolyte loss (rice-water stools)

10. Endotoxin ... effect

o Example: LPS in gram-NEG bacteria.

o Effect: Trigger systemic inflammatory responses, including septic shock

10. Exotoxins who+3 types

o PROTEINS secreted by gram-positive AND gram-negative bacteria.

o Categories:

§ AB Toxins (e.g., diphtheria toxin).

§ Cytolysins (e.g., pore-forming toxins).

§ Superantigens (e.g., TSST-1).

10. Lipid-like Toxin - example

o Example: Mycolactones.

o Function: Immune modulation and tissue destruction

11. Excretion vs. Secretion (2 examples)

o Excretion: Passive release of waste products outside the cell.

o Secretion: Active transport of specific proteins or compounds outside the cell for functional roles (TAT and SEC examples)

11. (Tat) System stand for, what

Twin Arginine Translocation

o Primary Function: Exports FOLDED proteins across bacterial membranes.

o Key Feature: Signal sequence with twin arginine residues targets the protein to Tat machinery.

memory trick ... FOLDED TAT - FOLD TAT - fold that or FLAT FOLD

11. General Secretory (Sec) System Role

Translocates UNFOLDED precursor proteins across membrane

memory trick ... unfolded for sec ... un-sex ... uni-sex

11. General Secretory (Sec) System Components

- SecYEG Translocon: Forms a channel for protein passage.

- SecB Protein: Chaperone that prevents premature folding of precursor proteins.

- Signal Peptidase: Cleaves signal sequences upon translocation

11. Type I Secretion System (T1SS)

o Directly transports proteins from the cytoplasm to the extracellular space.

o Components: Inner membrane ATP-binding cassette (ABC) transporter, periplasmic adaptor, and outer membrane protein.

1=direct abc

**11. Type III Secretion System (T3SS) + 3 species examples

o Function: Injects effector proteins into host cells via injectisomes.

o Pathogenic Examples:

§ Yersinia, Shigella, and Salmonella use T3SS for host manipulation.

o Chaperones: Stabilize effector proteins and deliver them to the secretion apparatus

3=inject

*11. Type IV Secretion System (T4SS)

o Highly versatile: Transports DNA and proteins INTO HOST cells via its protein complex

o Major Role: Contributes to horizontal gene transfer, including AMR

4=dna, protein ... HGT,AMR

***11. Type V Secretion System (T5SS)

o Features: Proteins utilize autotransporters to move across the outer membrane.

o Mechanism: Signal sequence directs translocation, and the β-domain forms a pore.

5=autotransporter, pore (5 auto beta)

11. Quorum Sensing

Communication via autoinducers coordinates bacterial behavior

**11. Type VII Secretion System (T7SS)

o Found in Mycobacterium species.

o Role of ESX-1: Virulence factor for immune evasion and intracellular survival

7-X-myco

11. 2 Types of Autoinducers

- AHLs (Acyl-homoserine lactones): Used by gram-NEG bacteria.

--rachel is negative

- AIPs (Autoinducing peptides): Utilized by gram-POS bacteria.

--apes are positive

11. Quorum Sensing Role in Infection of Host

Role in Infection: Enables synchronization of virulence factor production during infection - more damage to host this way bc more vir. factors made

*11. Lux System in Vibrio fischeri

a model for quorum sensing

o Mechanism: AHLs autoinducers BINDS to LuxR, activating bioluminescence genes.

Thus, bacteria Vibrio fischeri is gram NEG (negative rachel)

*11. Agr System in Staph aureus : 3 Components

- agrD: Encodes AIP precursor. daip

- AgrC and AgrA: Regulate virulence gene expression. cavir

*11. Yersinia pestis Pathogenicity

o Pathogenicity: Employs T3SS to inject effector proteins into host immune cells, suppressing inflammation.

Yersinia 3 suppressor

11. Yersinia pestis Adaptation

o Adaptation: Temperature-dependent LPS modifications enhance virulence.

11. Streptococcus pyogenes

SecA2 accessory system assists in delivering effector proteins to the host (Sec type means is moving unfolded proteins into host bc uni-sex)

12. Antimicrobial Bacteriostatic vs. Bactericidal types

o Bacteriostatic: Inhibits bacterial growth but may allow regrowth if treatment stops.

o Bactericidal: Kills bacteria directly.

12. Bacteriostatic vs. Bactericidal drug examples

Antibiotics targeting protein synthesis are often bacteriostatic, while cell wall-targeting drugs are bactericidal.

12. Minimum Inhibitory Concentration (MIC)

o Definition: The lowest concentration of an antibiotic that inhibits VISIBLE bacterial growth.

o Clinical importance: Determines the effective DOSE for treatment.

12. Kirby-Bauer Assay

o Purpose: Evaluates antibiotic susceptibility using zones of inhibition.

o Zone measurement: Diameter of the clear area around an antibiotic disk

12. Drug Development Phases Challenges

o Preclinical trials are time-consuming and expensive.

o High failure rates in discovering effective and safe compounds.

12. Targeting Unique Bacterial Features + Example

o Bacterial-specific targets reduce toxicity to human cells.

o Example: Targeting peptidoglycan synthesis absent in eukaryotes.

*12. Cell Wall Synthesis Inhibitors - main 3

Beta-lactams, Bacitracin, Vancomycin

*12. Beta-lactams - impact, examples, AMR

Inhibit transpeptidases, essential for peptidoglycan cross-linking, leading to cell lysis bc cell wall cannot be made right.

§ Examples: Penicillin, cephalosporins.

§ Resistance: Beta-lactamases hydrolyze the beta-lactam ring.

*12. Bacitracin - impact, what is bactoprenol

BLOCKS the dephosphorylation of bactoprenol, essential for cell wall precursor transport

*12. Vancomycin - impact, AMR

Prevents cross-linking by BINDING to the D-Ala-D-Ala terminal.

§ Resistance: Alteration of D-Ala-D-Ala to D-Ala-D-Lac in Enterococcus

***12. Daptomycin drug

Inserts into membranes, causing membrane depolarization and cell death

12. Protein Synthesis Inhibitors - 2 drug types

Aminoglycosides + Tetracyclines

**12. Aminoglycosides - impact, types, limits

Bind to the 30S ribosomal subunit, causing misreading of mRNA (e.g., gentamicin, kanamycin)

-Limitations: Ototoxicity and nephrotoxicity (hearing loss, kidney damage)

12. Tetracyclines

Prevent tRNA binding to the ribosome (Tetra for Trna)

12. Nucleic Acid Synthesis Inhibitor main drugs

Fluoroquinolones

12. Fluoroquinolones - impact, AMR

Inhibit DNA gyrase and topoisomerase IV ... necleic acid synthesis inhibitors

--- Vulnerability: AMR via mutations in target enzymes makes this drug ineffective

*12. Metabolic Pathway Inhibitors - main drug example

SULFANOMIDES inhibit folic acid synthesis

12. AMR - Efflux pumps

o Energy-driven transporters that expel antibiotics from the cell.

o Example: RND family pumps in gram-NEG bacteria (efflux...Reflex...RND...use atp0

12. AMR - Beta-lactamase Production - impact, counteraction

o Hydrolytic enzymes that deactivate beta-lactams.

o Counteraction: Beta-lactamase inhibitors like clavulanic acid restore drug efficacy

***12. mecA and PBP2a are used in _

altering the binding sites of the drug - mecA gene in MRSA encodes protein PBP2a, resistant to beta-lactams bc drug cannot as easily bind this protein

12. MRSA

Methicillin-resistant Staphylococcus aureus

12. gram NEG barrier

possess an outer membrane that limits drug entry

--Porin (in gram neg outer) mutations further restrict access

12. Mycobacterium tuberculosis AMR

o Resistance through efflux pumps and cell wall modifications.

o Persister cells (dormant, do not interact w/ drugs so they survive) contribute to treatment failure by entering a dormant state

*12. Vancomycin-Resistant Bacteria specific example

Alteration of the cell wall target prevents vancomycin BINDING to bacteria Enterococcus (vanco-entero)

*12. Healthcare-Associated Infections (HAIs) - 3 bacteria

Pseudomonas aeruginosa, Klebsiella pneumoniae, and ESBL-producing

Enterobacteriaceae ... (Extended-spectrum β-lactamases (ESBLs) are resistant to narrow-spectrum β-lactams, β-lactamase inhibitors, and later-generation extended-spectrum β-lactams.)

HAI - K,PA,ESBL

12. HAI contributing factors

o Overuse and misuse of antibiotics.

o Poor infection control in healthcare settings.

12. Biofilms - protect, cells

o Biofilms protect bacteria from antibiotics and host immune system.

o Persister cells within biofilms survive antibiotic treatment and regrow when conditions improve.

*12. Persister cells are in both

biofilms and M. tuberculosis

*12. 5 TA system example as a TA system

o REGULATE stress responses and persistence of bacteria bc antitoxin can stop toxin

o Example: Type V TA (5 TA) systems promote survival under stress by modulating translation.

*12. Multidimensional Approach to AMR Management Recommendations

o Antibiotic stewardship: Rational use to slow resistance development.

o Combination therapy: Using synergistic drugs to overcome resistance.

o Infection control: Improved sterilization and hygiene practices

13. Opportunistic Infections

Infections caused by microorganisms that typically coexist with the host without causing harm but exploit weakened defenses or breaches in barriers

13. Opportunistic Infection 2 gram POS examples

Staph epidermis and Candida albicans

13. Staph epidermis is a _ bc_

Staphylococcus epidermidis: Commonly part of the normal skin flora but causes infections in immunocompromised individuals or on medical devices.

13. Candida albicans

Candida albicans: A normal flora that can cause infections under conditions like immune suppression or antibiotic use.

13. flora

Microbial flora, also known as normal flora or indigenous microbiota, refers to the microorganisms that live in or on a host, such as bacteria and other organisms

13. Conditions Promoting Opportunistic Infections - 3

o Immunosuppression (e.g., HIV, chemotherapy).

o Use of invasive devices (e.g., catheters, prosthetics).

o Disruption of natural microbiota (e.g., broad-spectrum antibiotics).

13. Primary or True Pathogens

Microorganisms capable of causing disease in healthy individuals due to INHERENT virulence factors

13. True Pathogens - 2 examples

Strep pneumoniae and EHEC and M. tuberculosis

13. Strep pneumoniae can lead to/cause

Causes pneumonia and meningitis by invading healthy tissues

13. Salmonella enterica

Infects intestinal tissues and disseminates through host defenses

13. True Pathogens Key Features

o Ability to attach to and invade host tissues.

o Production of toxins (e.g., pneumolysin toxin made by Strep pneumoniae).

o Evasion of immune responses (e.g., polysaccharide capsules).

13. Distinction Between Opportunistic and True Pathogens

· Opportunistic pathogens rely on host vulnerability.

· True pathogens have mechanisms to breach normal host defenses in healthy individuals.

13. Pangenome of Gram-positive Opportunistic Pathogens

The complete set of genes in a species, including: core + accessory genes

13. Pangenome gram-POS Core genes

Essential for basic survival

*13. Pangenome gram-POS Accessory genes

Provide adaptability, including virulence and resistance traits

13. Accessory genes % and role

Accessory genes make up 80% of the pangenome in gram-positive opportunistic pathogens, contributing to AMR and biofilm formation

*13. Staph epidermis forms_ and lacks_

o Forms BIOFILMS, aiding in persistence on medical devices.

o LACKS aggressive toxins but relies on persistence mechanisms.

13. Staph epidermis vs aureus

o S. epidermidis forms smaller, less pigmented colonies and has fewer virulence factors.

o S. aureus produces toxins like TSST-1 and alpha-hemolysin.

*BOTH OPPURTUNISTIC

*13. Staph epidermis Adaptations to living on human skin

Resistance to osmotic stress via poly-γ-glutamic acid (PGA), helping survival under high salt conditions

*13. Staph epidermis Biofilms - role + human prevention

o Biofilm formation protects against antibiotics and immune defenses.

o Human prevention strategies ... antimicrobial coatings (e.g., silver) and surface modifications on implants.

13. T or F capsule is a vir. factor ?

T in strep pneumoniae

13. Which bacteria has specific at-risk populations and who are they

Strep pneumoniae=risk populations................o Major cause of death globally, especially in children under five.

High-risk = young children, the elderly, and immunocompromised individuals

*13. Strep pneumoniae 3 vir. factors

Pneumolysin, capsule, hyaluronidase

13. Strep pneumoniae - Pneumolysin

Cytotoxin that damages host epithelial cells and activates the immune response

13. Strep pneumoniae - Capsule

Prevents phagocytosis by immune cells

13. Strep pneumoniae - Hyaluronidase

Degrades CT connective tissues, aiding in spread and invasion

*13. Strep pneumoniae process - 2 parts

o Colonization of the nasopharynx as an asymptomatic reservoir.

o Entry into the BLOODSTREAM through tissue damage or immune evasion.

*13. Influenza virus 2ndy bacteria infection

Influenza VIRUS damages respiratory epithelium and reduces mucociliary clearance, increasing susceptibility to SECONDARY S. pneumoniae infections