Nguyen Lectures Flashcards
1
Q
T or F: planktonic bacteria live as communities
A
F - Planktonic bacteria live as motile single cells
2
Q
What are biofilms?
A
Multicellular bacterial communities
3
Q
T or F: Biofilm formation is limited to only a few unique species (ie. biofilms are unique phenomena)
A
F
4
Q
Most bacteria in environment exist as indvl bacteria or as biofilms?
A
Biofilms
5
Q
Contrast biotic and abiotic surfaces
A
Biotic surface = surface on living organism (ex. tissue)
Abiotic surface = surface on non-living thing (ex. rock)
6
Q
T or F: biofilms can be caused by many bacterial species living together. If true, what is this type of biofilm called?
A
T, called polymicrobial biofilm
7
Q
Are antibiotics effective against biofilms?
A
No
8
Q
T or F: biofilm-mediated infections are simple to treat
A
F
9
Q
Name 2 Gram - models for biofilm formation
A
- P. aeruginosa
2. E. coli
10
Q
Name 2 Gram + models for biofilm formation
A
- B. subtilis
2. S. aureus
11
Q
Name 2 ways that biofilms can be grown in the lab
A
- Grown on plastic plates
2. Grown as pedicles in liquid culture
12
Q
T or F: Biofilms can only form on solid surfaces
A
F - they can form in liquid broth as pedicles
13
Q
At which part of a liquid broth culture do pedicles form?
A
Air-liquid interface
14
Q
What microscopy technique is commonly used to study biofilms? What is its advantage?
A
Confocal microscopy. Can study the biofilm structure in 3D, which is useful bc bacteria form complex 3D structures in biofilms
15
Q
Describe the method used to quantify biofilm formation
A
Grow biofilms on polystyrene/plastic plates (Calgary device), then stain with crystal violet
16
Q
Name 5 components in the extracellular polymeric substances matrix
A
- environmental DNA
- polysaccharides
- proteins
- cellular debris
- membrane vesicles
17
Q
List 2 reasons why the composition of the matrix can be different
A
- different bacteria form different matrices
- different matrices form depending on the environment - bacteria will form different proteins and molecules depending on the environment and nutrients available
18
Q
List 3 properties of the environment that can influence matrix composition
A
- nutrients
- physical
- chemical
19
Q
List 2 functions of the matrix
A
- keeps the cells aggregated
2. keep the aggregated cells stuck to the surface
20
Q
T or F: transition from biofilm state to planktonic state is an unregulated and random process
A
F: gene regulation and coordinated gene expression is required for biofilm formation and transition into planktonic state
21
Q
What does EPS stand for
A
extracellular polymeric substance
22
Q
What are 2 properties of EPS polymers?
A
- adhesive
2. aggregative
23
Q
Give 2 reasons why biofilms are difficult to get rid of. Consider properties of the EPS matrix
A
- acts as a protective barrier by slowing diffusion of molecules like antibiotics - prevents these molecules from reaching the bacteria
- acts as a protective barrier by interfering with immune functions (ex. prevents Ab from reaching bacteria)
24
Q
What is quorum?
A
Density of bacteria
25
List 4 things that quorum sensing can regulate
1. light production
2. virulence factor production
3. biofilm formation
4. antibiotic production
26
What is quorum sensing?
- bacterial communication signal based on surrounding bacterial density
- allows bacteria to regulate gene expression
27
T or F: gene expression correlates linearly with cell density in quorum sensing
F: Cells must reach a critical density before there is enough of an auto-inducing signal that activates a transcriptional regulator to turn on gene expression
28
T or F: quorum sensing is not a good target for drugs aiming to inhibit biofilm formation
F
29
List 3 strategies that can be used to treat biofilm infections
1. Develop compounds/surfaces that prevent attachment
2. Develop matrix-degrading enzymes
3. Target biofilm metabolism + dispersion
30
Name 3 properties of chronic infections
1. Less invasive
2. More localized
3. Less susceptible to antibiotics
31
Why are biofilm infections considered chronic infections?
1. Motility and virulence factor genes are turned off
2. Matrix prevents bacteria from disseminating into system/limits bacterial spread
- overall, this promotes low "visibility" of the bacteria to the immune system = less inflammation
- also, immune cells and Ab can't reach bacteria due to matrix, therefore bacteria persist
32
T or F: most antibiotics originate from a synthetic/man-made source
F - most are derived from natural compounds produced by environmental bacteria
33
T or F: bacteriostatic antibiotics kill bacteria
F - they INHIBIT bacterial growth. removing the drug will allow the bacteria to resume growing
34
Bacteriostatic drugs target what bacterial process?
Cell replication
35
Bactericidal drugs inhibit a process required for _____.
Cell survival
36
T or F: Whether a drug is cidal or static depends on concentration and the bacterial species targeted
T
37
How are antibiotic classes grouped?
Based on what they target
38
What are the 3 major targets of antibiotics?
1. cell wall synthesis
2. protein synthesis
3. DNA replication
39
What do beta-lactams target?
Cell wall biosynthesis/peptidoglycan cross linking
40
Where are drug efflux pumps located on Gram negative bacteria?
Spans the inner and outer membranes
41
What is the function of a drug efflux pump?
Pumps antibiotics and other bad molecules from cytoplasm to ECS
42
T or F: drug efflux pumps are specific
F
43
T or F: drug efflux pumps are mechanisms of multidrug resistance
T - bc the pumps are not specific and can prevent many different antibiotics from reaching their target
44
T or F: expression of drug efflux pumps can be regulated
T
45
Give an example of a target mutation.
Mutation in gyrase so quinolone cannot bind to it
46
Give an example of an enzyme that performs drug modification
Beta lactamase
47
What is meant by the spectrum of a beta-lactamase?
How specific the beta-lactamase is - the less specific, the broader the spectrum
48
What is the consequence of a broad-sepctrum beta-lactamase? What are these enzymes called ?
Called super beta-lactamases - can cleave many beta lactamases
49
Give 2 examples of drug modification
1. Enzymes degrading the antibiotic
| 2. Enzymes adding moieties to the antibiotic
50
Which class of drugs are often modified by the additional of chemical moieties?
Aminoglycosides
51
List 3 methods of horizontal gene transfer
1. Transduction - phage injects DNA from bacterium A to B
2. Conjugation - direct transfer of plasmids from one bacterium to another
3. Transformation - pick up eDNA
52
What is vertical transmission of antibiotic resistance?
After a selective pressure is applied to a resistance-heterogenous population, all the bacteria are resistant. Only the resistant bacteria survived, so all the others died
53
T or F: more antibiotics are used on animals than on humans
T
54
What is the issue with using antibiotics on animals? 2 reasons
1. Bacteria on the animal/in the animal may become drug resistant. People will eat the animal + bacteria, and may develop drug-resistant infections
2. Antibiotics end up in wastewater and in natural environments, creating a selective pressure - basically brewing antibiotic-resistant environmental bacteria, which may then transfer their DNA to pathogens
55
Why are new antibiotics quickly become useless because bacteria quickly become resistant to them?
They are based on old antibiotics, so it's easy to develop a mutation that blocks mechanism of the new antibiotic
56
List 3 strategies in overcoming antibiotic resistance
1. changing human behaviour - use antibiotics properly
2. find new antibiotics/use combinations of antibiotics
3. inactivating resistance mechanisms (ex. find inhibitors for beta-lactamases, find ways to inhibit efflux pumps)
57
How were the ESKAPE pathogens selected?
1. Associated with multidrug resistance
| 2. Very common, therefore dangerous if it acquires drug resistance
58
T or F: antibiotics are only natural compounds
F - can be natural or synthetic (but based on molecules found in nature)
59
Do all antibiotics kill bacteria?
No, some are bacteriostatic - just need to inhibit replication, then allow immune system to take care of clearing infection
60
List the 3 main steps of cell wall synthesis
1. polyglycan synthesis
2. adding peptides to polyglycans (Sortase system)
3. transpeptidation - link all the polyglycans
61
Which step of cell wall synthesis do beta-lactams target? How?
Transpeptidation step; beta-lactams resemble D-Ala-D-Ala which is the normal substrate for penicillin binding protein. Acts as a competitive inhibitor so that the D-Ala-D-Ala are never linked
62
List some examples of beta lactams
```
Penicillin
Cephalosporin
Carbapenem
Ampicillin
Amoxicillin
Monobactam
```
63
What do the different substituents on the common beta-lactam ring do?
Make them more resistant to beta-lactamases
64
Are beta-lactams mostly used against Gram + or - bacteria
Gram +
65
What part of the elongation step in translation do aminoglycosides inhibit?
tRNA translocation
66
What part of the elongation step in translation do tetracyclines inhibit?
tRNA delivery
67
List 2 examples of 30S subunit inhibitors
Tetracyclines
| Aminoclycosides
68
List 3 examples of 50S subunit inhibitors
Chloramphenicol
Lincosamides
Macrolides
69
What do chloramphenicol and lincosamides do?
Inhibit peptidyl transferase
70
What do macrolides do?
inhibit peptide exit tunnel so protein cannot be released
71
T or F: aminoglycosides are effective against Gram +
F
72
What types of bacteria are aminoglycosides effective against?
Gram negatives
| Facultative anaerobes
73
Are aminoglycosides mainly cidal or static?
Cidal
74
T or F: most protein synthesis inhibitors have bacteriostatic activity
T
75
Are quinolones cidal or static?
Cidal
76
T or F: quinolones have broad spectrum activity against Gram +, -, and quinolones
T
77
List 2 methods used to improve old antibiotics
1. chemical optimization
| 2. combination therapy
78
List 3 methods of combination therapy
1. combine with another antibiotic
2. combine with molecule that overcomes resistance (clavulanic acid)
3. combine with molecule to increase penetration into bacterial
79
List 3 side effects of antibiotics
1. antibiotic resistance
2. short term infections (C. difficile infections)
3. disruptions to microbiota
80
List 2 new classes of antibacterial molecules
Teixobactin
| Odilorhabdins - 30S subunit inhibitor
81
What are the 5 steps of biofilm formation
1. initial attachment
2. irreversible attachment + cell replication
3. early biofilm formation
4. biofilm maturation
5. biofilm dispersal
82
Bacteria in biofilms stick to surfaces via ___ and ___
surface appendages
| adhesion molecules
83
What do surface appendages of bacteria in biofilms include?
Flagella and pili
84
T or F: molecules mediating attachment can adhere specifically or non-specifically on biotic surface of host
T
85
T or F: polymer composition of the EPS is species-specific
T
86
Are there high or low levels of cyclic di-GMP in biofilm state?
High
