Midterm Flashcards
1
Q
What are Koch’s original postulates?
A
- Microbe must be associated with the symptoms of disease and must be present at the infection site.
- The microbe must be isolated from the lesions of disease and grown as a pure culture.
- A pure culture, when innoculated into a susceptible host, must reproduce the disease.
- Microbe must be re-isolated in the pure culture from the experimentally infected host.
2
Q
When regarding global causes of mortality, what type of infections are most deadly?
A
Lower respiratory infections
3
Q
In low-income countries, what are the four most common bacteria causes of death?
A
- Neonatal conditions (infections/sepsis)
- Lower respiratory infections
- Diarrhoeal diseases
- Tuberculosis
4
Q
What is the definition of pathogenicity?
A
The ability of an organism to cause disease (damage the host).
5
Q
What is the definition of virulence?
A
The degree of pathology caused by the organism.
6
Q
What is the definition of infectivity?
A
A pathogen’s capacity for horizontal transmission and how frequently it spreads among hosts.
7
Q
What are the two common measures to define virulence?
A
- Infectious dose (ID50)
- Mortality (%)
8
Q
What is ID50?
A
The dose of bacteria at which 50% of hosts are infected.
9
Q
What types of bacteria utilize endo-sporulation?
A
Gram positive
10
Q
What is endo-sporulation?
A
A tough structure that can withstand extreme external environments.
11
Q
What type of bacteria utilize dessication resistance?
A
Gram negative
12
Q
What is dessication resistance?
A
Prevents drying out
13
Q
What is metabolic versatility?
A
The ability to utilize multiple nutrient sources.
14
Q
What is dormancy?
A
Remain in a state of starvation (inactivation) and use minimal resources.
15
Q
What is genome plasticity?
A
The ability to rearrange genes and/or acquire new ones.
16
Q
What is xenobiotic efflux?
A
Movement of toxi compounds out of the cell.
17
Q
What are the ten bacterial survival strategies?
A
- Endo-sporulation
- Dessication resistance
- Metabolic versatility
- Dormancy
- Genome plasticity
- Colonization of another host
- Mobility and chemotaxis
- Alteration of membrane properties
- Xenobiotic efflux
- Biofilm formation
18
Q
What is bacterial attachment in biofilms mediated by?
A
Polysaccharide slime - acts like a glue
19
Q
What are the molecular Koch’s postulates?
A
- Pathogenic trait should be associated with the pathogenic members of the genus, species, or strain.
- Inactivation of the gene associated with the pathogenic trait should result in a measurable loss of pathogenicity or virulence.
- Reversion or allelic replacement (complementation) of the mutated gene should restore pathogenicity.
20
Q
What is the goal of the molecular postulates?
A
To prove that a gene product is an essentual virulence factor.
21
Q
What are the five common steps in bacterial infection?
A
- Entry into the host body for colonization
- Evasion of host defenses
- Obtain nutrients, multiply to significant numbers and spread
- Damage the host and produce disease
- Transmission from infected to susceptible host
22
Q
What are the five types of flagella?
A
- Monotrichous (polar)
- Lophotrichous
- Peritrichous
- Amphitrichous
- Internal
23
Q
What type of flagella is shown?
M
A
Monotrichous
24
Q
What type of flagella is shown?
A
Lophotrichous
25
What type of **flagella** is shown?
Amphitrichous
26
What type of **flagella** is shown?
Peritrichous
27
**Motility** is directed by the ability to sense one or more of which **four things**?
1. Chemicals (chemotaxis)
2. Light (phototaxis)
3. Oxygen (aerotaxis)
4. Magnetic fields (magnetotaxis)
28
What is an **example** of entry into the host relating to **motility and taxis**?
E. coli UTIs - urine is nutrient rich, E. coli gains access to the bladder by a combination of motility and chemotaxis.
29
**Mucin** acts as a *blank* and traps *blank*.
1. Lubricant
2. Bacteria
30
**Mucin** prevents *blank* from accessing/binding to *blank*.
1. Microbes
2. First layer of cells
31
**Mucin** is expelled by what?
Goblet cells
32
True or false: mucin is uniform across the cell surface.
False - it is patchy.
33
What is the **lamina propria**?
The thin layer of loose connective tissue underneath the epithelial cells - can be a site of infection.
34
What four things can be utilized for **adhesion**?
1. Flagella
2. Pili
3. Fimbriae
4. Afimbrial adhesions
35
What is **host and tissue tropism**?
The way in which viruses/pathogens have evolved to preferentially target specfic host species, tissues, or cell types.
36
What lies at the **root** of **tropism**?
Adhesion between ligands on the bacterium and receptors on the host, or vice versa.
37
What is the **charge** on a **defensin**?
Positive
38
How do some **human defensins** work?
By disrupting bacterial cytoplasmic membranes.
39
What are three strategies for overcoming **host antibacterial peptides**?
1. Secreting peptidases
2. Synthesizing capsule polysaccharide layers (works by limiting diffusion)
3. Lipopolysaccharide binding (gram negative)
40
What are the **two solutions** for overcoming **minimal Fe availability**?
1. Don't use Fe
2. Acquire sequestered Fe
41
What bacteria uses **manganese** instead of Fe?
B. burgdorferi
42
What is an example of an **alternative pathway** that doesn't involve Fe?
Siderophores
43
What is a **siderophore**?
A low molecular weight compound that chelate Fe with high affinity.
44
In what **two ways** can a pathogen exist **extracellularly**?
1. Interstitial spaces, blood, lymph
2. Epithelial surfaces
45
In what **two ways** can a pathogen exist **intracellularly**?
1. Cytoplasm
2. Vesicles
46
In what **two ways** can **toxins** be categorized?
1. Non-proteinaceous (endotoxin) - eg. lipopolysaccharides
2. Proteinaceous (exotoxin) - eg. A-B toxins, proteolytic toxins, pore forming toxins, other toxins
47
What is a **spreading factor**?
Proteins like DNases and proteases that facilitate spread into neighbouring tissues.
48
What **three things** make up the first line of **innate immunity defenses**?
1. Skin
2. Mucous membranes and secretions
3. Normal flora
49
What **four things** make up the second line of **innate immune defenses**?
1. Innate immune cells
2. Inflammation
3. Complement
4. Antimicrobial substances
50
What makes up the **third line adaptive immune defenses**?
1. B cells - antibody production
2. T cells - helper and killer
51
True or false: there is little variation in epithelial cells between different locations.
False - there is large variation.
52
True or false: different areas of epithelia have specialized defense mechanisms.
True
53
What does **SALT** stand for?
Surface associated lymphoid tissue
54
What are the **six defenses** of epithelia?
1. Dry, acidic environment
2. Dead, keratinzed cells
3. Sloughing of surface cells
4. Toxic lipids, lysozyme
5. Normal microbiota
6. Underlying immune cells (Langerhans, etc)
55
What is a **Langerhans cell**?
A dendritic cell that processes invading bacteria and activates specific defenses - APCs.
56
What are the **seven sites** of epithelia and **their defenses**?
1. Eyes - tears
2. Airway entrance - muscus, cilia
3. Stomach - acid
4. Small intestine - rapid flow, sloughing
5. Colon - resident microbiotia, skoughing, flow
6. Vaginal tract - resident microbiota, sloughing, flow
7. Bladder - sphincter, flushing
57
What is the **mucociliary elevator**?
Mucus producing goblet cells and ciliated epithelium - cilia continuously beat and push mucus coated bacteria out of the body.
58
Some commensals produce *blank* compounds.
Bactericidal.
59
What are the **three categories** of **innate immune cells**?
1. Phagocytes - neutrophils, macrophages, dendritic cells
2. Natural killer cells
3. Mast cells - non-phagocytic, congregate in blood vessels, release granules of histamine
60
What are the **two routes** for **transmigration** into tissue?
1. Paracellular (between endothelial cells)
2. Transcellular (through endothelial cells)
61
Different *blank* molecules are produced in the *blank* of different tissues, which bind to *blank* expressed on the surface of *blank*.
1. Adhesion
2. Vasculature
3. Specific receptors
4. Neutrophils
62
**Chemokines** bind to receptors on neutrophils and induce what?
Comformational changes in integrins to allow for binding with ligands along the endothelium.
63
True or false: neutrophil sites for transmigration are random.
False - they are actively chosen by the cell
64
What is an **opsonin**?
An antibody or other substance (like complement) that bind to foreign microorganisms and increase phagocytosis of them.
65
Antibodies and C3b are recognized by **which receptors** on the surface of neutrophils?
1. FcR
2. C3bR
66
Opsonization **facilitates** what?
Molecular recognition of a microbe by a neutrophil.
67
What are three steps of **killing pathogens** in a phagocyte?
1. Fusion of phagosome with the lysosome
2. Phagolysosome - release of lysozyme, proteases, defensins, peroxide, superoxide, hyperchlorous acid, nitric oxide - degradation of bacteria
3. Release of bacterial fragments
68
What **five toxic compounds** are produce in the **phagolysosome**?
1. Hypochlorous acid (from myeloperoxidase)
2. Superoxide anion (via NADPH oxidase)
3. Singlet oxygen
4. Hydrogen peroxide and hydroxyl radicals
5. Reactive nitrogen species (from nitric oxide synthase)
69
What is a **synergystic pathogen**?
A pathogen that amplifies the effects of another pathogen.
70
What are the **difficulties** when it comes to modelling **polymicrobial infections**?
1. Complexity of pathogen relationships
2. Host-specific factors (immune response, microbiomes, pre-existing disease)
3. Establishment and maintenance of a polymicrobial environment in non-human hosts
4. In vitro does not replicate the host environment
71
Why are there few **lung metagenomics** studies?
1. Low microbial burden samples
2. High human genetic material content
3. Not cost effective
72
Why are **anaerobes** a problem in **CF lung infections**?
CF lungs have an oxygen gradient much more severe than non-diseased lungs - provides opportunities for more anaerobic bacteria to grow.
73
What is the **future of therapeutics** related to **polymicrobial lung infections**?
1. Phage therapy - nebulization of phages into lungs to get rid of nasty pathogens
2. Community restoration - restoration of the typical microbiota found in the lungs after nasty pathogens are removed.
74
**Chronic** *Pseudomonas aeruginosa* is associated with what five things?
1. Worsened baseline lung function
2. Increased rate of FEV decline
3. Increased exacerbation frequency
4. Poorer nutritional status
5. Worsened radiographic scores
75
Regarding the **natural history of lung infection**, from what ages does a CF patient have intermittent P. aeruginosa infections?
0-20
76
Regarding the **natural history of lung infection**, from what ages does a CF patient have chronic P. aeruginosa infections?
20+
77
What are the **five** limitations of **in vitro susceptibility** testing of CF sputum **pathology**?
1. Antibiotics aren't used in isolation - many patients will be on multiple
2. Organisms grow differently in the lung vs in the lab - mode of growth, biofilms, permeated by microcolonies, typically see a reduction in susceptibility by a magnitude of 2-3x
3. Hetergeneity in infecting populations - extremely diverse population due to chronic infections and antibiotic use over decades
4. CF lungs are extremely anoxic due - testing results are very different in an anoxic environment
5. Organisms beyond what the clinical lab identifies - microbiota can impact environment and change the effect of antibiotics
78
What is a **biobank**?
Consists of every pathogen isolated from many patients
79
What **five things** can a **biobank** show regarding bacterial pathogenesis?
1. The natural history of infection
2. Infection transmission through time
3. Detailed collection of clinical outcome records
4. Infectious contributors to lung disease
5. Biomarkers of infection
80
What type of cells is **MHC class I** found on?
All nucleated cells and platelets.
81
What type of cells is **MHC class II** found on?
Antigen presenting cells - B-cells, DCs, macrophages, neutrophils, etc
82
**STAT3** (Tfh) T-cells have a role in **what**?
Class-switching (long-term humoral immunity)
83
**STAT6** (Th2) T-cells have a role in **what**?
Antibody production by B-cells
84
**STAT4** (Th1) T-cells have a role in **what**?
Macrophage activation
85
**STAT3** (Th17) T-cells have a role in **what**?
Neutrophil activation
86
**STAT5** (iTreg) T-cells have a role in **what**?
Immune tolerance, lymphocyte homeostasis
87
What are the **five** major classes of **antibodies**?
1. IgG
2. IgA
3. IgE
4. IgM
5. IgD
88
Which antibody is the major **circulating antibody**?
IgG - found in extracellular fluid, blood, lymph, and can cross the placenta
89
Which antibody is the **first produced**?
IgM
90
IgA is found **where**?
In body secretions - saliva, tears, breast milk, colostrum, gastrointestinal secretion, mucus - present in secretions as a dimer.
91
What are the **four** major functions of **antibodies**?
1. Neutralization
2. Agglutination of particles
3. Precipitation of soluble antigens
4. Complement fixation (activation)
92
What are two examples of **neutralization** by an antibody?
1. Blocking viral binding sites
2. Coating bacteria/opsonization
93
Which **antibody function** leads to cell lysis?
Complement activation
94
What are the **eight** molecular determinants of **virulence** in P. aeruginosa?
1. Extracellular polysaccharides
2. Lipopolysaccharides (LPS)
3. Small molecules
4. Flagellum
5. Type III secretions
6. Type VI secretions
7. Secreted extracellular factors
8. Pilus
95
In what **two ways** does P. aeruginosa target and kill **host cells**?
1. ExoS (T3S-dependent)
2. ExoA (T3S-independent)
96
How does **ExoS** impact the function of a **host cell**?
1. Host cell FAS activates ExoS
2. ExoS modifies Ras (transfer ADP onto the molecule) and disrupts its ability to participate in signal transduction
3. Ras regulates growth and cell division
4. Prevents immune response and promotes apoptosis
| **Injected into the cell by T3SS
97
How does **ExoA** impact the function of the **host cell**?
Targets EF-2 and disrupts protein synthesis - causes necrosis and leads to systemic infections.
| **Secreted by general secretions pathway
98
What are the three parts of the **Type III Secretion System** in P. aeruginosa?
1. Basal body - Anchors the system in the membrane
2. Needle complex - Penetrates the host membrane
3. Translocon - Pore forming structure that allows effector proteins to pass into the host cell
99
**Quorum sensing** in **gram-negative** organisms involves which two regulatory components?
1. Transcriptional activator protein (R protein)
2. Autoinducer molecule -> AHL (produced by autoinducer synthase)
100
Which **molecule** is responsible for **quorum-sensing** in P. aeruginosa?
Acylhomoserine lactones (AHL)
101
What is the **general** explanation of **quorum sensing** in P. aeruginosa?
Low cell density -> low AHL -> no transcription of target gene
High cell density -> high AHL -> transcription of target genes
102
What are the **two domains** of the **R protein**?
1. N terminus - interacts with autoinducer
2. C terminus - DNA binding
103
Why is **quorum sensing** important for reduced immune detection?
Rapid, high level expression occurs once threshold is met - immune system doesn't have time to launch targeted attack.
104
What are **three advantages** of biofilms?
1. Protects cells from the immune system
2. Active starvation responses in the depths of community activate antioxidant defenses
3. Protects bacteria from the activity of antibiotics
105
How do **biofilms** prevent antibiotic damage?
1. Polymers in the matrix traps antibiotics - protects the cells below the zone of sequestration
2. Only cells in the outer layer die
3. Cells beneath this zone are metabolically active and respond by initiating a stress respond
106
What is the **purpose** of **penicillin binding proteins** in staph?
Transpeptidases - catalyze transpeptidation of peptidoglycan (present in cell wall of bacteria)
107
Which **gene** does *mecA* encode?
PBP2' (resistant to methicillin)
108
What does **SSCmec** encode for?
Cassette chromosome recombinase (ccrAB)
109
What is the purpose of **ccrAB**?
Mediates site-specific excision and integration of the mobile genetic element.
110
What is **SCCmec**?
A mobile genetic element that encodes for mecA (methicillin resistance).
111
What is **autotransduction**?
The transfer of genetic material containing antibiotic resistance to susceptible bacterial cells via bacteriophages.
112
What are the **six virulence factors** utilized by S.aureus?
1. Hemolysins
2. Leukocidins
3. Proteases
4. Enterotoxins
5. Exfoliative toxins
6. Immune modulatory factors
113
How is the **complement system** interrupted by S.aureus?
CHIPS (chemotaxis inhibitory protein of staphylococci) binds to the C5a receptor, and SCIN (staphylococcal complement inhibitor) mediates a blockade of C3 convertase activity.
114
How is **opsonophagocytosis** interrupted by S.aureus?
Staphylococcal Protein A (SpA) binds to host antibodies and prevents opsonophagocytosis and contribute to apoptosis of B cells.
115
How is **endothelial integrity** compromised in S.aureus?
S.aureas alpha toxin (Hla) causes direct injurt to the endothelium, disrupting integrity of the endothelial barrier.
116
How are **leukocytes** damaged by S.aureus?
They are targeted and injured by bi-component leukocidins, phenol soluble modulins, and alpha-toxin.
117
What are the **four leukocidins** in S.aureus?
1. PVL
2. LukAB/GH
3. LukED
4. Hlg
118
How is S.aureus able to create **deep abscesses** of infection?
When neutrophils release NETs (DNA), S.aureus is able to convert this material to deoxyadenosine, which triggers the caspase-3-dependent death of immune cells. Leads to local inflammation, infarction, and fibrin encapsulation.
119
What **toxin** from S.aureus causes **toxic shock syndrome**?
TSST-1 (toxic shock syndrome toxin 1) - pyrogenic toxin superantigen.
120
How does **TSST-1** activate **T-cells**?
By crosslinking the variable beta-chain of the TCR to the alpha chain of the MHCII molecule of an APC.
121
What **percentage** of T-cells are activated by **PTSAg**?
Up to 20%
122
Once **T-cells** are activated in **toxic shock syndrome**, what occurs?
They release a proinflammatory cytokine called IFN-gamma, which signals for macrophages to release additional inflammatory cytokines (IL-6, IL-1, TNF-alpha).
123
What is the role of **C3b and C3bi** in complement?
Labelling of bacteria - opsonization
124
What are the four steps of an **experiment** to **evaluate virulence factors**?
1. Dilute bacteria to a known concentration
2. Infect host - assess success of initial innoculation
3. Allow animals to get sick - compare wildtype to mutant time-wise
4. Harvest organs and assess bacterial growth and pathology
125
What is the role of **C3d** in complement?
Antigen presentation
126
What is the role of **C5a** in complement?
Chemoattractant - activation of endothelium to make "sticky"
127
What is the role of the **C56789n** complex in complement?
Lysis of gram-negative bacteria
128
**Phagocytosis** by **neutrophils** is dependent on **what**?
Opsonization of targets
129
How does S.aureus interfere with **neutrophil extravasion**?
Molecules like SSL-5 and SSL-11 interfere with the rolling process of neutrophil recruitment by binding to P-selectin glycoprotein ligand 1 (PSGL-1), which inhibits interactions between selectins along the endothelium. The molecule EAP interferes with adhesion by preventing binding with Intracellular adhesion molecules (ICAMS).
130
How does S.aureus **kill and block** neutrophil activation?
1. TLR inhibitors like SSL-3
2. Toxins like PSMs, leukocidins, etc
3. Chemotaxis inhbitors like CHIPS, SCIN, and SSL-5
131
How does S.aureus **evade opsonization**?
1. C3 convertase is inhibited by SCIN and SCIN B-C
2. C3 is inhibited by SBI and aureolysin
2. C3b is inhibited by SBI and SAK
3. C5 convertase is inhibited by EFB, ECB and SSL-7
4. C5a is inhibited by SepA
132
How does **intracellular growth** protect bacteria from **antibiotics**?
Antibiotics are largely unable to penetrate cell membranes, and are therefore unable to reach pathogens within a cell. This can potentially be overcome by the use of liposomes, which are able to bypass the cellular membrane.
133
What is the role of **MPO**?
Myeloperoxidase - catalyzes the production of hypochlorous acid and reactive oxygen species to kill pathogens in neutrophils.
134
What is the role of **NETs**?
DNA, antimicrobial proteins, and histones expelled from neutrophils to trap pathogens.
135
What is the role of **Kuppfer cells**?
Liver-resident macrophages that clear blood-bourne pathogens
136
What is the role of **staphyloxanthin**?
A pigment that protects S. aureus from oxidative killing by neutrophils.
137
What is the role of **protein A**?
Prevents opsonization and phagocytosis - disrupts B-cell function.
138
Why is iron **essential**?
It is used as a cofactor for many key properties due to it's redox properties.
139
In which **heme proteins** is iron **essential**?
1. Cytochromes (ETC, oxidative phosphorylation)
2. Hemoglobin (oxygen transport)
3. Oxygen activation (Oxidases)
140
In which **non-heme proteins** is iron **essential**?
1. Fe-S cluster proteins (ETC, nitrogen fixation)
2. Enzymes used in DNA synthesis (ribonucleotide reductase)
141
Why is **iron toxic**?
Because it can catalyze RO species (hydroxyl radicals) which are highly toxic and can quickly form additional free radicals which results in cellular injury.
142
What is the concept of **nutritional immunity**?
The fact that iron is highly sequestered in living organisms - specialized systems for acquisition, distribution, and storage of iron leads to essentially no 'free' itron in the body.
143
What is **transferrin**?
Dietary and recycled iron is transferred to transferrin, and is then carried to cells requiring it. Iron-loaded Tf is taken up by receptor-mediated endocytosis, iron is removed, and the vesicle is delivered back to the cell surface and released.
144
What is **lactoferrin**?
A homologue of Tf - apo-Lf is produced by neutrophils and glandular epithelial cells. Lf is present on mucosal surfaces and at sites of inflammation and is involved in innate immunity. When N-terminal region is released -> lactoferricin (a protease and cationic antimicrobial peptide).
145
What group does **hydroxamate** siderophores contain?
-CONHOH (hydroxamate)
146
What group does **catecholate** siderophores contain?
OH groups on a benzene ring (catechol)
147
What is **TonB-dependent uptake**?
1. An iron bound siderophore complex binds to TonB-dependent transporter on bacterial outer membrane
2. The TonB-ExbB-ExdD complex on the inner membrane utilizes the chemosmotic potential to interact with the TonB complex and mediate ATP-dependent uptake into the bacterial cytoplasm
148
What is **siderocalin** (NGAL)?
A protein with the ability to bind enterobactin with similar affinity as the bacterial siderophore receptor - produced and secreted onto mucosal surface in response to pathogenic bacteria.
149
What is a **hemophore**?
Bacterial molecules that bind heme and the receptors that transport them.
150
What is **hemophore mediated uptake**?
Hemophores and heme-binding proteins extract heme from hemoglobin, myoglobin, and hemopexin. Heme is released and captured by surface proteins.
151
What is involved in the **direct uptake/binding** of heme?
Surface receptors that are able to directly bind heme containing proteins such as hemoglybin, myoglobin, and hemopexin - main receptors include IsdB, IsdH, and HarA.
152
What is involved in **binding of host iron-glycoproteins**?
Some gram-negative bacteria possess host-specific receptors for Tf or Lf and allow them to survive within the body. Involves TbpB (transferrin binding protein B), TbpA, ExbB, ExdD, TonB, FbpB/C and FbpA.
153
What is the **iron-regulated surface determinant** system (isd)?
The extraction of heme and subsequent shuttling of heme through the cell wall by Isd proteins is facilitated by NEAr iron transporter (NEAT) domains.
154
What is included in the **upper respiratory tract**?
1. Nasal cavity
2. Pharynx
3. Larynx
155
What is included in the **lower respiratory tract**?
1. Trachea
2. Primary bronchi
3. Lungs
156
What is the **epiglottis**?
Cartilaginous tissue that prevents food from moving into the airway.
157
What is **hemin**?
A protoporphyrin IX containing Fe3+ and a coordinating Cl- ligand.
158
What is **natural competence/natural transformation**?
Efficient uptake of exogenous DNA and integration into the chromosome - relies on DNA elements called uptake signal sequences (USS). Strains and species with a common USS are a reservoir for antigenic variation.
159
What is the *Neisseria* counterpart to **USS**?
DNA uptake sequence - DUS.
160
What are the **five steps** of **natural trannsformation**?
1. DNA binding
2. DNA import
3. DNA transfer to ComEC
4. ssDNA entry into the cell
5. Recombination
161
What happens in the **DNA binding** step of **natural transformation**?
1. DNA sequences (DUS or USS) are recognized and bound by surface-exposed Type IV pilus
2. ComE and ComEA proteins help to transport the DNA across the membrane through PilQ
162
What happens in the **DNA import** step of **natural transformation**?
DNA is brought into cell as the pilus retracts due to the Pil Complex BCTM (basal core transport membrane).
163
What happens in the **DNA transfer** step of **natural transformation**?
DNA is moved into the cytoplasm by the ComEC-RecB channel with the help of ComEA proteins.
164
What happens during **ssDNA entry into the cell** in **natural transformation**?
ssDNA is moved into the cell through the ComEC-RecB complex, one strand is degraded by nucleosomes so only one strand remains.
165
What happens during **recombination** during **natural transformation**?
The ssDNA is protected by SSBs (single-stranded binding proteins) and RecA recombinase facilitates homologous integration of the DNA into the bacterial chromosome.
166
What is **antigenic variation**?
The expression of functionally conserved moieties within a clonal population that are antigenically distinct.
167
What is **gene conversion**?
The process by which one DNA sequence replaces a homologous sequence in the genome.
168
What is **phase variation**?
Caused by slipped-strand mispairing which has a much higher frequencies than mutation that cause 'on' or 'off' expression - allows selection to work on the bacterial population and can occur in non-coding regions by affecting promoter spacing.
169
How does *Neiserria* attach to **brain endothelium**?
1. T4P binds to the CD147-beta2AR complex
2. CD147-beta2AR is highly expressed in brain endothelium, giving this organism tropism for this tissue
3. This interaction initiates a signalling cascade that breaks down tight junctions.
170
What is a **disinfectant**?
An antimicrobial agent that is applied to non-living objects and surfaces.
171
What is an **antiseptic**?
An antimicrobial substance applied to living tissues
172
What is an **antibiotic**?
A substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dlution.
173
What does **bacteriostatic** mean?
Inhibits bacterial growth
174
What does **bactericidal** mean?
Kill bacterial cells.
175
What is the **mode of killing** in **alcohol disinfectants**?
Denaturing of proteins
176
What is the **mode of killing** in **alkylating agent disinfectants**?
Forms epoxide bridges that inactivate proteins
177
What is the **mode of killing** in **phenol disinfectants**?
Denature proteins and disruption of cell membranes by intercalating in them.
178
What is the **mode of killing** for **QAC disinfectants**?
Disrupt cell membranes by intercalating in them
179
What is the **mode of killing** for **UV radiation disinfectant**?
Blocks DNA replication and transcription by damaging DNA,
180
What is the idea of **one health AMR**?
The recognition of the interconnection between people, animals, plants and their shared environment and shaping health goals and outcomes based on this.
181
What **class** of antibiotics interrupts **cell wall synthesis**?
Beta-Lactams - includes penicillins, cephalosporins, carbapenems and monobactams.
182
Which **two** antibiotics interrupt **nucleic acid synthesis**?
Folate synthesis - sulfonamides, trimethoprim
183
What **five antibiotics** impact 50S **synthesis**?
1. Macrolides
2. Clindamycin
3. Linezoid
4. Chloramphenicol
5. Streptogramins
184
What **five things** are involved when discussing the nature of **polymicrobial lung infections**?
1. Microbial interactions
2. Synergistic effects
3. Competition for resources
4. Impact on disease severity
5. Antibiotic resistance
185
What is molecular function of **extracellular polysaccharides** in P. aeruginosa?
They typically function as adhesins - allowing anchoring to other cells and maintainence biofilms
186
What is the molecular function of **flagellum** in P. aeruginosa?
Allows for motility and chemotaxis towards preferred substrates.
187
What is the molecular function of some **secreted extracellular factors** in P. aeruginosa?
1. Hemolytic phospholipase C - cleaves RBC membrane
2. DNases - useful against NETs
188
What is the molecular function of **type IV secretion (T6S) effectors** in P. aeruginosa?
Mediation of the horizontal gene transfer - facilitates transferring of useful genes such as antibiotic resistance.
