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MIMM465: Bacterial Pathology > Nguyen Lectures > Flashcards

Nguyen Lectures Flashcards

1
Q

T or F: planktonic bacteria live as communities

A

F - Planktonic bacteria live as motile single cells

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2
Q

What are biofilms?

A

Multicellular bacterial communities

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3
Q

T or F: Biofilm formation is limited to only a few unique species (ie. biofilms are unique phenomena)

A

F

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4
Q

Most bacteria in environment exist as indvl bacteria or as biofilms?

A

Biofilms

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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)

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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

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7
Q

Are antibiotics effective against biofilms?

A

No

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8
Q

T or F: biofilm-mediated infections are simple to treat

A

F

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9
Q

Name 2 Gram - models for biofilm formation

A
  1. P. aeruginosa

2. E. coli

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10
Q

Name 2 Gram + models for biofilm formation

A
  1. B. subtilis

2. S. aureus

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11
Q

Name 2 ways that biofilms can be grown in the lab

A
  1. Grown on plastic plates

2. Grown as pedicles in liquid culture

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12
Q

T or F: Biofilms can only form on solid surfaces

A

F - they can form in liquid broth as pedicles

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13
Q

At which part of a liquid broth culture do pedicles form?

A

Air-liquid interface

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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

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15
Q

Describe the method used to quantify biofilm formation

A

Grow biofilms on polystyrene/plastic plates (Calgary device), then stain with crystal violet

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16
Q

Name 5 components in the extracellular polymeric substances matrix

A
  1. environmental DNA
  2. polysaccharides
  3. proteins
  4. cellular debris
  5. membrane vesicles
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17
Q

List 2 reasons why the composition of the matrix can be different

A
  1. different bacteria form different matrices
  2. different matrices form depending on the environment - bacteria will form different proteins and molecules depending on the environment and nutrients available
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18
Q

List 3 properties of the environment that can influence matrix composition

A
  1. nutrients
  2. physical
  3. chemical
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19
Q

List 2 functions of the matrix

A
  1. keeps the cells aggregated

2. keep the aggregated cells stuck to the surface

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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

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21
Q

What does EPS stand for

A

extracellular polymeric substance

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22
Q

What are 2 properties of EPS polymers?

A
  1. adhesive

2. aggregative

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23
Q

Give 2 reasons why biofilms are difficult to get rid of. Consider properties of the EPS matrix

A
  1. acts as a protective barrier by slowing diffusion of molecules like antibiotics - prevents these molecules from reaching the bacteria
  2. acts as a protective barrier by interfering with immune functions (ex. prevents Ab from reaching bacteria)
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24
Q

What is quorum?

A

Density of bacteria

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25
Q

List 4 things that quorum sensing can regulate

A
  1. light production
  2. virulence factor production
  3. biofilm formation
  4. antibiotic production
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26
Q

What is quorum sensing?

A
  • bacterial communication signal based on surrounding bacterial density
  • allows bacteria to regulate gene expression
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27
Q

T or F: gene expression correlates linearly with cell density in quorum sensing

A

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

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28
Q

T or F: quorum sensing is not a good target for drugs aiming to inhibit biofilm formation

A

F

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29
Q

List 3 strategies that can be used to treat biofilm infections

A
  1. Develop compounds/surfaces that prevent attachment
  2. Develop matrix-degrading enzymes
  3. Target biofilm metabolism + dispersion
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30
Q

Name 3 properties of chronic infections

A
  1. Less invasive
  2. More localized
  3. Less susceptible to antibiotics
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31
Q

Why are biofilm infections considered chronic infections?

A
  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
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32
Q

T or F: most antibiotics originate from a synthetic/man-made source

A

F - most are derived from natural compounds produced by environmental bacteria

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33
Q

T or F: bacteriostatic antibiotics kill bacteria

A

F - they INHIBIT bacterial growth. removing the drug will allow the bacteria to resume growing

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34
Q

Bacteriostatic drugs target what bacterial process?

A

Cell replication

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35
Q

Bactericidal drugs inhibit a process required for _____.

A

Cell survival

36
Q

T or F: Whether a drug is cidal or static depends on concentration and the bacterial species targeted

A

T

37
Q

How are antibiotic classes grouped?

A

Based on what they target

38
Q

What are the 3 major targets of antibiotics?

A
  1. cell wall synthesis
  2. protein synthesis
  3. DNA replication
39
Q

What do beta-lactams target?

A

Cell wall biosynthesis/peptidoglycan cross linking

40
Q

Where are drug efflux pumps located on Gram negative bacteria?

A

Spans the inner and outer membranes

41
Q

What is the function of a drug efflux pump?

A

Pumps antibiotics and other bad molecules from cytoplasm to ECS

42
Q

T or F: drug efflux pumps are specific

A

F

43
Q

T or F: drug efflux pumps are mechanisms of multidrug resistance

A

T - bc the pumps are not specific and can prevent many different antibiotics from reaching their target

44
Q

T or F: expression of drug efflux pumps can be regulated

A

T

45
Q

Give an example of a target mutation.

A

Mutation in gyrase so quinolone cannot bind to it

46
Q

Give an example of an enzyme that performs drug modification

A

Beta lactamase

47
Q

What is meant by the spectrum of a beta-lactamase?

A

How specific the beta-lactamase is - the less specific, the broader the spectrum

48
Q

What is the consequence of a broad-sepctrum beta-lactamase? What are these enzymes called ?

A

Called super beta-lactamases - can cleave many beta lactamases

49
Q

Give 2 examples of drug modification

A
  1. Enzymes degrading the antibiotic

2. Enzymes adding moieties to the antibiotic

50
Q

Which class of drugs are often modified by the additional of chemical moieties?

A

Aminoglycosides

51
Q

List 3 methods of horizontal gene transfer

A
  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
Q

What is vertical transmission of antibiotic resistance?

A

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
Q

T or F: more antibiotics are used on animals than on humans

A

T

54
Q

What is the issue with using antibiotics on animals? 2 reasons

A
  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
Q

Why are new antibiotics quickly become useless because bacteria quickly become resistant to them?

A

They are based on old antibiotics, so it’s easy to develop a mutation that blocks mechanism of the new antibiotic

56
Q

List 3 strategies in overcoming antibiotic resistance

A
  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
Q

How were the ESKAPE pathogens selected?

A
  1. Associated with multidrug resistance

2. Very common, therefore dangerous if it acquires drug resistance

58
Q

T or F: antibiotics are only natural compounds

A

F - can be natural or synthetic (but based on molecules found in nature)

59
Q

Do all antibiotics kill bacteria?

A

No, some are bacteriostatic - just need to inhibit replication, then allow immune system to take care of clearing infection

60
Q

List the 3 main steps of cell wall synthesis

A
  1. polyglycan synthesis
  2. adding peptides to polyglycans (Sortase system)
  3. transpeptidation - link all the polyglycans
61
Q

Which step of cell wall synthesis do beta-lactams target? How?

A

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
Q

List some examples of beta lactams

A 
Penicillin 
Cephalosporin
Carbapenem
Ampicillin 
Amoxicillin 
Monobactam
63
Q

What do the different substituents on the common beta-lactam ring do?

A

Make them more resistant to beta-lactamases

64
Q

Are beta-lactams mostly used against Gram + or - bacteria

A

Gram +

65
Q

What part of the elongation step in translation do aminoglycosides inhibit?

A

tRNA translocation

66
Q

What part of the elongation step in translation do tetracyclines inhibit?

A

tRNA delivery

67
Q

List 2 examples of 30S subunit inhibitors

A

Tetracyclines

Aminoclycosides

68
Q

List 3 examples of 50S subunit inhibitors

A

Chloramphenicol
Lincosamides
Macrolides

69
Q

What do chloramphenicol and lincosamides do?

A

Inhibit peptidyl transferase

70
Q

What do macrolides do?

A

inhibit peptide exit tunnel so protein cannot be released

71
Q

T or F: aminoglycosides are effective against Gram +

A

F

72
Q

What types of bacteria are aminoglycosides effective against?

A

Gram negatives

Facultative anaerobes

73
Q

Are aminoglycosides mainly cidal or static?

A

Cidal

74
Q

T or F: most protein synthesis inhibitors have bacteriostatic activity

A

T

75
Q

Are quinolones cidal or static?

A

Cidal

76
Q

T or F: quinolones have broad spectrum activity against Gram +, -, and quinolones

A

T

77
Q

List 2 methods used to improve old antibiotics

A
  1. chemical optimization

2. combination therapy

78
Q

List 3 methods of combination therapy

A
  1. combine with another antibiotic
  2. combine with molecule that overcomes resistance (clavulanic acid)
  3. combine with molecule to increase penetration into bacterial
79
Q

List 3 side effects of antibiotics

A
  1. antibiotic resistance
  2. short term infections (C. difficile infections)
  3. disruptions to microbiota
80
Q

List 2 new classes of antibacterial molecules

A

Teixobactin

Odilorhabdins - 30S subunit inhibitor

81
Q

What are the 5 steps of biofilm formation

A
  1. initial attachment
  2. irreversible attachment + cell replication
  3. early biofilm formation
  4. biofilm maturation
  5. biofilm dispersal
82
Q

Bacteria in biofilms stick to surfaces via ___ and ___

A

surface appendages

adhesion molecules

83
Q

What do surface appendages of bacteria in biofilms include?

A

Flagella and pili

84
Q

T or F: molecules mediating attachment can adhere specifically or non-specifically on biotic surface of host

A

T

85
Q

T or F: polymer composition of the EPS is species-specific

A

T

86
Q

Are there high or low levels of cyclic di-GMP in biofilm state?

A

High

MIMM465: Bacterial Pathology (6 decks)

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