Progress Exam 4 (November 12 - 13 - 14 - 15) Flashcards

Question

PmrA model

Answer 1

* High pH --> non-active PmrA --> no transcription (is the promotor region blocked? * Low pH --> active PmrA --> active transcription --> effector proteins (Icm/Dot): modification vacuole

Answer 2

Repression by steric hindrance

Answer 3

Class I activation Class II activation or Activation by conformation change

Answer 4

* Ankyrin repeats * Coiled-coil domains * Tetratricopeptide repeats * F box-domains * Fic domains

Answer 5

Salmonella, Campylobacter, VRE, ESBL + E. coli, H7N7 and other avian influenzas

Answer 6

MRSA and hepatitis E virus genotype 3

Answer 7

Bovine Spongiform Encephalopathy --> vCJD

Answer 8

* Respiratory infections * Atypical pneumonias * Hospital admissions of his patients

Answer 9

* 60% asymptomatic * 20% flu-like (head ache, fever, nausea, muscle pain) * 20% serious (persisting fever, chest pain, severe head ache, diarrhoea, vomiting, often: atypical pneumonia * 1 - 3% chronic infection: endocarditis and other intravesicular infections.

Answer 10

* IgG-phase 2 antibodies in the acute setting * IgG-phase 1 antibodies in chronic Q-fever

Answer 11

Doxycycline

Answer 12

Combination therapy

Answer 13

1. Culling of all infected herds. 2. Vaccination of all healthy goats. 3. Ban on all goat transports.

Answer 14

40% CT content

Answer 15

Agricultural affairs and economics should not have been allowed to prevail over public health.

Answer 16

Mycoplasma infections *C. burnetii* infections

Answer 17

Maximize the absorptional capacity

Answer 18

Crypt with Paneth cells, CBC cells (stem cells)

Answer 19

Toxic to stem cells, but energy source for epithelial cells

Answer 20

* Dietary compounds * Vitamins * Fiber (short chain fatty acids) * Immunity training * Inflammation regulation * Pathogen resistance

Answer 21

Increase in bodyfat after the transplantation

Answer 22

Already increases the vascular network comparable to the vascular network after whole microbiota transplantation

Answer 23

Fecal microbial transplantation (FMT)

Answer 24

* Small intestine villi and crypts * Large intestines only crypts

Answer 25

Microbiota, mucus layer and colon epithelium. Recirculation of oxygen-rich media

Answer 26

Muc2 shows that the GuMi maintains intact monolayers and multiple cell types.

Answer 27

Changed cytokine/chemokine profile and gene expression in the presence of CD4+ T cells. Changes immune responses and calm down colon epithelium.

Answer 28

*Staphylococcus aureus*

Answer 29

1. Antimicrobial-releasing coatings 2. Contact-killing surfaces 3. Nonadhesive surfaces 4. Ideal multifunctional coatings

Answer 30

* Reduced adherence of bacteria: hydrophilic surface * Reduced adherence of plasma proteins: polymeric phospholipids/polyethylene glycol PEG

Answer 31

* Benzalkonium chloride heparin

Answer 32

* Antiseptics: chlorhexidine-silver sulfadiazine * Metals: silver, silveroxide * Antibiotics: minocydin + rifampin, gentamicin * Antimicrobial peptides

Answer 33

* Antibiotics in endosomes * Bacteria in phagosomes Antibiotics don't reach bacteria. Releases of antibiotics because of illumination and the response of photosensitizers. IBIZA – Photo treatment

Answer 34

* Biofilms * Tissue (intracellular) colonization

Answer 35

Biomaterials together with bacteria. Can be either pro- or anti-inflammatory.

Answer 36

Caused by *Borrelia burgdorferi*

Answer 37

By hard bodied Ixodes ticks to humans (via a complex enzootic cycle).

Answer 38

* Erythema migrans * Lyme carditis * Lyme neuroborreliosis (mostly B. garinii) * Acrodermatitis chronica atrophicans (chronic skin infection) (mostly B. afzelii) * Lyme arthritis (mostly B. burgdorferi) * Borrelial lymphocytoma

Answer 39

*B. afzelii* Species complexity is higher in Europe *B. afzelii, B. aarinii, B. burgdorferi and B bavariensis*.

Answer 40

* 31 kDa membrane lipoprotein * Expressed by *Borrelia* in the mid-gut of an unfed tick * Tick feeding - OspA down regulation - upregulation of OspC - migration to salivary gland and host * Borrelia genospecies are categorized into several serotypes (ST) based on OspA protein i.e. OspA ST1 - ST6

Answer 41

C-terminal part is immunogenic and contains protective epitope.

Answer 42

1. Tick ingest OspA antibodies while feeding (blood meal) on vaccinated host 2. Ingested antibodies binds spirochetes expressing OspA in the tick mid-gut before OspA down regulation 3. Migration to salivary gland is blocked 4. Spirochete elimination is reported to be independent of host complement*

Answer 43

1. rOspA vaccinated human produces IgG anti-OspA antibodies 2. Tick consumes anti-OspA during feeding on vaccinated human 3. Anti-OspA antibodies bind to OspA on *Borrelia* bacteria and kills the bacteria 4. Migration of the bacteria to tick salivary gland and to the vaccinated human is blocked. 5. Vaccinated human is protected against LD.

Answer 44

LYMErix and ImuLyme. Official reason (fall): lack of demand leading to poor sales.

Answer 45

* Chimeric OspA vaccines * OspA ferritin nanoparticle vaccine

Answer 46

* VLA15 is a combination of 3 proteins * Broad protection (pre-clincial murine model) - 4 genospecies representing 6 STs * Phase I (first in humans; safety trial) - Phase II (dose optimization trial) * Large phase III (efficacy and safety trial, by Pfizer) * **Attachment of the C-terminals of different OspA ST1 to 6**

Answer 47

Multiple epitopes on one protein as they did for fHBP *N. meningitidis* (variant 1, 2 and 3). They took the backbone of variant 1 and added the immunogenic epitopes from variant 2 and 3. 1 protein induced bactericidal antibodies against all meningococcus B strains tested.

Answer 48

High sequence similarity (identity) was observed between the C-termini of OspA ST1-ST6

Answer 49

* **Step 1**: sequence conservation analysis ST1-ST6 * **Step 2**: homology modeling/structural scaffold. They used *B. afzelii* ST2 (conserved backbone) * **Step 3**: surface partitioning. Based on monoclonal antibody (mAb) binding to template OspA ST1. * **Step 4**: patch layouts. 6 multivalent vaccines were designed and assessed in animal models. * **Step 5**: serotype distribution. * **Step 6**: mouse model immunogenicity and efficacy analysis.

Answer 50

1. Immunize C3H/HeN mice with antigen 2. Collect immune sera and do IgG ELISA, flow cytometry and serum bactericidal assay. 3. In-vitro grown borrelia or infected tick (ticks off) 4. Collect final sera and organs and do serology VlsE (variable major protein like sequence expressed) + ELISa

Answer 51

* Variants 1 and 4 (disulfide bond C) – excluded due to low protein yields and lower immune responses * Variants 2, 3, 5 and 6 were tested for efficacy in murine models

Answer 52

V3 and V5 linked together with a 23 amino acid long linker sequence **P66 protein** of *B. aarinii* strain PBr. V3-L2-V5 has higher antibody titres than FL-OspA ST1, ST4, ST5 and ST6 and similar to FL-OspA ST2 and ST3.

Answer 53

As the reciprocal of the lowest dilution showing 50% bacterial killing.

Answer 54

* High immune response against major OspA STs * Highly potent - 100% protection against OspA ST1 and ST2 (significant protection 3 ng dose (ST1)) * Potential protection against other STs since high immune responses were observed * Single antigen vaccine – economically viable (cost-effective)

Answer 55

* *Ixodes* ticks most important vector Northern hemisphere. * Carry multiple tick-borne pathogens, among which *Borrelia burgdorferi* genospecies. * Lyme disease incidence increasing. * LD diverse clinical manifestations. * No human vaccine against LD (anymore/yet)

Answer 56

* Emergence of other tick-borne diseases (TBEV, BMD, Babesiosis etc.) * Need for improved serodiagnostics LD and other TBDs * Etiology, diagnosis & treatment of PTLDS (post-treatment LD symptoms) * Necessity for a human vaccine to prevent LD.

Answer 57

Cellular immune responses and humoral (IgG) are involved in tick immunity

Answer 58

* 187 AA protein * There are homologs in other tick species * Top hit protein from *Varroa destructor* * Highly immunogenic (IgG antibodies produced) * No effect on tick feeding * RNAi of tsgp1 - succesful silencing yet no effect on tick feeding.

Answer 59

Enhanced TSGP1 expression in salivary glands of ticks infected with *Borrelia*

Answer 60

TSGP1 boosts *Borrelia* infectivity in mice

Answer 61

Vaccination against TSGP1 partially protects against *Borrelia*

Answer 62

* Redness increased after challenges * Itch increased * Similar weights * More dead ticks T-cell, B-cell, neutrophils, eosinophils present in the tissues.

Answer 63

* Induced upon tick feeding * Enhanced expression upon *Borrelia* infection in ticks * Boosts *Borrelia* infectivity in mice * Significantly protects against *Borrelia* when used as an anti-tick vaccine.

Answer 64

* Mosquito * Sporozoite * In the liver/hepatocyte: schizont * Infecting RBCs * Asexual blood stage: erythrocyte - ring - trophozoite - schizont - merozoite * Gametocyte stage (mosquito drinks this) * Microgamete * Zygote + macrogamete * Ookinete * Oocyst * Start all over again

Answer 65

*Anopheles*

Answer 66

Protozoa Small unicellular parasites

Answer 67

* *P. falciparium* * *P. vivax* * *P. ovale* * *P. malariae*

Answer 68

* *P. falciparium* * *P. vivax* * *P. ovale* (Curtesi and Walekeri) * *P. malariae* * *P. knowlesi* (zoonosis)

Answer 69

Patients can be most ill but infection is not lethal in most cases

Answer 70

Serious disease often with lethal outcome and requires immidiate treatment

Answer 71

* *P. falciparum* has high parasitaemia (increasing levels) * *P. vivax + P. ovale* only invade young erythrocytes * *P. malariae* invades old erythrocytes * *P. falciparum* can infect the organs: blocking of small blood vessels i.e. in brain.

Answer 72

PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1)

Answer 73

1. Children 2. Non-immune people (travelers) 3. Pregnant women

Answer 74

Through antigenic variation

Answer 75

* Age * Gravidity * Endemicity * HIV status

Answer 76

* Pregnancy associated malaria: A pregnancy in which malaria infection occurs (can be asymptomatic) * Placental malaria: A malaria infection that invests the placenta (and not necessarily the periphery and can be asymptomatic as well (no acute disease)

Answer 77

CD36 receptor

Answer 78

A sulfated glycosaminoglycan present on the syncytiotrophoblast in the intervillous space of the placenta, normally functions as a reversible immobilizer for cytokines, hormones and other molecules.

Answer 79

* IgG antibodies of malaria immune primigravidae are not able to recognize the VAR2CSA antigen, because this pregnancy specific antigen differs from malaria antigens expressed in non-pregnant hosts. Primigravidae are therefore more susceptible to placental malaria. * Elevated levels of immunosuppressive pregnancy hormone cortisol increase susceptibility in primigravidae

Answer 80

Elevated levels of IL-10

Answer 81

Fetal growth restriction might be caused by elevated levels of TNF-a which impair materno–fetal exchanges by damaging placental host tissues.

Answer 82

Elevated levels of TNF-a and IFN-g Influences uterine contraction and inducing and activating abortion associated NK cells.

Answer 83

Elevated levels of TNF-a By inflicting oxidative stress on erythrocyte membranes, leading to an increased destruction of these erythrocytes or by its inhibitory effects on erythropoiesis.

Answer 84

reduction of the intervillous area exposed to maternal blood harming placental blood flow and impairing materno–fetal exchanges (growth restriction).

Answer 85

Gram-positive bacterium

Answer 86

* Transient versus chronic * Nasal carriage ~ 30% of population * Presence on skin, pharynx, groin * Carriage increases risk of infection

Answer 87

* Opportunistic pathogen * All barrier tissues (skin, lungs etc) * Hospital versus community-acquired * Surgical-site infections (implants)

Answer 88

* Neutrophils * T-cells (make IL-17 for attracting neutrophils)

Answer 89

* Polymorphic nucleus (3-lobed) * ~ 10¹¹ cells/day * Granules with hydrolases, peroxidases, defensins, lysozyme and lactoferrin * Migration via chemotaxis (IL-8, IL-17, C5a)

Answer 90

* NETosis (entrapment) * Opsonization with antibody or complement binding. Target the bacteria for phagocytosis.

Answer 91

No complement

Answer 92

1. Antibodies 2. Complement 3. T cells

Answer 93

1. Evasion of bacterial opsonization 2. Evasion of phagocytosis and killing 3. Targeting immune cells

Answer 94

* Interfering with antibody binding to bacterial surface (protein A) * Inhibition of the complement system (SCIN)

Answer 95

* Neutrophil recruitment to infection site: **CHIPS**: blocks C5a-receptor * Antibody-mediated phagocytosis: **FLIPr**: blocks Fcy-receptor * NET formation and proteases: **Eap**: blocks elastase and **nuclease**: degrades NETs

Answer 96

By producing a number of toxins and superantigens. **Toxins** * alpha-toxin: upon binding it oligomerizes and it forms a pore * Biocomponent pore-forming toxins (leukocidins): F-subunit and S-subunit or LukAB **T cell superantigens** Antigens that can bind outside of the TCR and increases the activation of T cells (~ 25%). Overactivation: hiding in plain sight.

Answer 97

* Accessory gene regulator * Quorum sensing * Auto-inducing peptides (AIPs) * Inhibits adhesion * Promotes invasion

Answer 98

* Immune evasion * Translation * Strain variation

Answer 99

Mice need a lot more *S. aureus* to get 50% mortality

Answer 100

* Iron acquisition/metabolism * Conserved and immunogenic antigen Phase 3 clinical trial (ineffective) * Prior *S. aureus* exposure makes the otherwise protective IsdB vaccine non-protective * IsdB vaccine recalls non-protective humoral memory from prior *S. aureus * infection

Answer 101

* CPS based (conjugated) vaccines succesful for other bacterial pathogens * *S. aureus*: two dominant capsule (sero-)types CP5 and CP8 Vaccine ineffective in hemodialysis patients. Only in specific situations and conditions this CPS is present. In vivo no expression. Dominant MRSA clones do not produce CPS (USA300)

Answer 102

* Pre-existing immunity * Suboptimal vaccine composition * Antigenic/phase variation * Variation in host susceptibility

Answer 103

* **Immune evasion**: neutralization of immune evasion (antibodies) * **Translation**: use pre-clinical models that better resemble human infection * **Strain variation**: target conserved or essential bacterial antigens

Answer 104

1. Formation of a acquired pellicle 2. Early colonizers that bind to the conditioning layer/pellicle 3. Late colonizers (all bind *F. nucleatum*) 4. Immune system responds to late colonizers Practice: not that straightforward

Answer 105

**Ecological succession** is the process of change in the species that make up an ecological community over time.

Answer 106

Buccal cells

Answer 107

A young biofilm. Oxygen levels are different

Answer 108

Lower oxygen levels in late colonizers

Answer 109

Human buccal cells and microorganisms associated with them are important in recolonization after brushing Early colonizers are in fact early proliferators.

Answer 110

Not random at all and actually very important.

Answer 111

* Oxygen levels change over time. * Anaerobic on the inside of the biofilm Changing in space and time: **spatio-temporal heterogeneity**

Answer 112

* Fungi * Archaea * Amoeba

Answer 113

Oxygen consumption that induces the growth of strict anearobic bacteria. Switch of metabolism from aerobic to a more anaerobic metabolism (fermentation etc.)

Answer 114

* Frequent sugar intake leads to selective pressure --> favor aciduric bacteria --> are also acidogenic bacteria * Increased caries risk

Answer 115

Sugars --> increase in cariogenic species --> increase in sugar fermentation --> increase in organic acids --> low pH --> higher caries risk and selection for cariogenic species --> cycle....

Answer 116

Iron Heme group is causing the red fluorescence

Answer 117

Accumulation of bacteria --> increased inflammatory mediators --> gingival inflammation --> increase in GCF leakage (gingival crevicular fluid) --> increase in protein and increase in iron --> favorable conditions for proteolytic bacteria + keystone pathogen mechanisms --> more inflammatory mediators --> cycle...

Answer 118

Total of all micro-organisms in a specific location. Micro-organisms: bacteria, fungi, protozoa and viruses. Microbiota + the theatre of activity (microbial structural elements and microbial metabolites)

Answer 119

Host and oral microbiome combined (in balance; homeostasis) Healthy oralome (**eubiosis**) or an unbalanced oralome (**dysbiosis**)

Answer 120

* Periodontitis * Endocarditis * Atherosclerosis * Alzheimer's Disease * Diabetes * Head and Neck Cancer

Answer 121

Detection of a dysbiosis at an early time point

Answer 122

No caries, no gingivitis, no erosion, no periodontitis, no mucositis, no halitosis.

Answer 123

The mother. Colonization starts at birth. Transmission through breast-feeding.

Answer 124

Hormonally driven gingivitis (not caused by bacteria). Bacteria will translocate to the placenta. Tregs recognize mother's microbiome as 'safe' are generated in fetal lymphoid tissue.

Answer 125

1. DNA structure: presence, amplification, rearrangement, modification (porA/pili) 2. Transcriptional regulation: activation, repression (Sigma factors, Fur) 3. Post-transcriptional regulation: translation repression, transcript stability (sRNA, riboswitch, RNAT)

Answer 126

Gene that has a common promoter. A set of neighboring genes in a genome that is transcribed as a single polycistronic message.

Answer 127

A set of target genes regulated by the same transcription factor by physically binding to regulatory motifs to accomplish a specific biological function. They use the same common regulator.

Answer 128

All the genes whose expression is increased or decreased by a specific external stimulus.

Answer 129

1. Essential to adapt to growth conditions encountered in the host. 2. To express bacterial virulence factors that are essential components for pathogenesis and enable the host to survive.

Answer 130

* Promoter (-35 . spacer (17 nt) . -10) * Start site transcription * A/T rich enhancer * Shine Dalgarno (SD) - ribosomal binding site (RBS) * Start site translation * Protein encoding gene (A/C rich codons) 5-UTR consists of everything between start site transcription and the start site translation.

Answer 131

Illegitimate base pairing in regions of repetitive DNA during replication: production of deletions or insertions of repeat units. **Example**: *porA* gene of *N. meningitidis* has expression variants of the outer membrane protein

Answer 132

The length of the DNA stretch (spacer) between the -35 and -10 box.

Answer 133

1. In direct contact with the DNA 2. Recognize specific promoter consensus sequences (-35 and -10 region) Is complexed with RNA polymerase: * Sigma 70 - general (housekeeping) * Sigma 32 - stress * Sigma E - heat shock * Sigma 54 - nitrogen A sigma factor (σ factor or specificity factor) is a protein needed for initiation of transcription in bacteria.

Answer 134

* Recognize specific sequences in or near promoter region * Have different modes of action Repressor proteins: steric hindrance, blocking elongation, DNA looping Activator proteins: class I activation, class II activation, activation by conformation change

Answer 135

* Specific promoter sequence recognition: sigma factors * Specific transcriptional regulators: Fur (Ferric Uptake Regulator) * Specific stimuli: Fe 50% of iron responsive genes are under control of Fur

Answer 136

Fur is a dimeric protein that has a high affinity for iron. Genes regulated by Fur are characterized by: consensus sequence: **Fur box** or **Fbs** (Fur binding site) (partially overlapping with promoter sequence)

Answer 137

NATWATNATWATNATWAT

Answer 138

* **Excess iron**: there's no need for the uptake of iron-complexed proteins. Fur binds Fe and is active. Active Fur binds to the Fur-box (no transcription) * **Low iron**: bacteria need iron, so expression of genes coding for receptors binding iron-complexed proteins on! Fur can't bind Fe which leads to a conformation change (in-active Fur). RNA polymerase can bind the Fur-box and there transcription of the coding region. Fur related genes are crucial for iron acquisition.

Answer 139

* Lactoferrin * Transferrin * Binding proteins

Answer 140

* sRNA (20-500 nt) encoded in the intergenic region or on anti-sense strand * Regulate stability and translation of mRNAs, often in conjunction with the conserved prokaryotic RNA chaperone protein **Hfq** * Antisense to the untranslated 5' region (5-UTR) of the target mRNA to be regulated.

Answer 141

By environmental stress. Target **mRNAs** often encode for stress responsive components. One sRNA can regulate more mRNA targets

Answer 142

A Fur box in their promoter region and ar Fur/iron regulated.

Answer 143

1. Translation repression by sRNAs 2. Translation activation by sRNAs 3. mRNA degradation because of the binding of sRNAs 4. Stabilizing mRNA because sRNA is bound (no ribonuclease able to bind anymore)

Answer 144

Riboswitches are located in the 5-UTR of the mRNAs. They change the structure of RNA in response to binding of a specific metabolite: * Guanidine * Adenosine * Lysine * SAM * Mg mRNA regulatory elements that control gene expression by altering their structure in response to specific metabolite binding.

Answer 145

* **Aptamer**: performs ligand recognition * **Expression platform**: regulates either transcription or translation initiation Some riboswitches also control mRNA decay

Answer 146

Sequesters (OFF switch) or Frees (ON switch) the RBS

Answer 147

RNATs are elements usually located in the 5-UTR of the mRNAs. They operate by changing structure in response to temperature fluctuation by a zipper like mechanism. Regulate expression of virulence genes of pathogens.

Answer 148

*prfA* Listeria that works together with riboswitch and sRNA. sRNA is transcribed from a riboswitch and controlled by a RNAT

Answer 149

Antimicrobial compounds produced by micro-organisms, especially bacteria.

Answer 150

1. Uncontrolled (over)use 2. Resistance spread by horizontal gene transfer (natural genetic competence, phage transduction and conjugation) 3. Lack of development of novel classes antibiotics

Answer 151

Too expensive since production is cheap, use is limited in time. Yet the development is as costly as any internal medicine (clinical trials phase I - III 100 - 500 10⁶ euro)

Answer 152

The study of its activity

Answer 153

Cytological profiling

Answer 154

Membrane depolarization or blocking of the cell wall synthesis.

Answer 155

* Bacterial cytological profiling showed delocalization of certain peripheral membrane proteins * No strong membrane depolarization * Daptomycin clusters fluid lipids (lipids with short and/or unsaturation and/or branched fatty acids) * This leads to detachment of peripheral membrane proteins (e.g. those with amphipathic alpha helix membrane anchors). Including essential N-acetylglucosamine transferase MurG involved in peptidoglycan synthesis precursor synthesis lipid II.

Answer 156

Tetracycline binds to ribosome blocking translation. * TEM (transmission electron microscopy) shows that tetracycline disturbs the cell membrane * Bacterial cell biology shows that tetracycline sits mostly in the cell membrane * Tetracycline can disturb the localization of certain peripheral membrane proteins, thus has an additional MOA

Answer 157

* Persister cells are antibiotic tolerant (not the same as antibiotic resistant!) * Cause of recurrent infections and resistance * Tolerant because they do not grow, or grow very slowly * Non growing cells occur in every bacterial culture * Persisters are an example of cellular heterogeneity in bacterial populations, which is common in bacterial cultures

Answer 158

That hey are removed by the immune system.

Answer 159

Bistable regulation (also called bimodal regulation. Other example: phenotypic switching due to phase variation, e.g. formation of different surface proteins and/or carbohydrates to evade the immune system)

Answer 160

* Regulation mechanism is simple and only requires (i) an autostimulatory loop * Threshold level for the activity of this loop (often cooperative binding of a transcription factor to DNA) * Stochastic fluctuations in gene expression (also called noise in gene expression)

Answer 161

* Bet-hedging * Division of labour

Answer 162

* Nutrient reduction in biofilms * Stringent response * SOS response * Toxin-antitoxin systems

Answer 163

Persister cells still have a membrane potential.

Answer 164

* Dissipation of membrane potential (by valinomycin) causes ROS (reactive oxygen species) that contribute to the killing including causing DNA damage * Many antibiotics cause ROS, primarily hydroxyl radicals likely due to release of Fe2+ ions from iron-sulfur containing proteins, triggering the Fenton reaction **Fenton reaction:** hydrogen peroxide conversion catalyzed by Fe2+ ions into hydroxyl radicals * However, not the case with depolarization using valinomycin, since iron chelators do not mitigate the effect moreover, superoxide dismutase mutant are sensitive, but katalase mutant not, indicating that superoxide radicals are formed and not hydroxyl radicals * Confirmed by using specific superoxide radical and hydroxyl radical scavengers * Electron transfer chain (ETC) well know source of ROS (also in mitochondria) * Only ETC mutant that mitigated the effect of valinomycin was inactivation of the conserved Rieske protein (QcrA), which is also present in mitochondria * **Rieske protein** contains Fe2+ and is a well know source of superoxide radicals in mitochondria * Bacterial cell biology experiments showed that this protein detaches from the other components of the Cytochrome BC complex (QcrB, QcrC) In TB inactivation of Rieske protein increases the resistance to membrane dissipating antibiotics (now explained). Many bacteria do not contain Rieske protein but their persisters are still killed by membrane depolarization, likely linked to ROS formation. How is not know (but important to discover)

Answer 165

*Staphylococcus epidermidis (CoNS)* and *S. aureus*

Answer 166

With sutures way less *S. aureus* infection than in people without sutures.

Answer 167

1. Adherence 2. Maturation/growth 3. Detachment

Answer 168

* Quorum sensing * Difficult to phagocytose * Not effectively reached by all antibiotics * In dormant state, less susceptible to antibiotics * Persisters * A persisting inflammatory stimulus

Answer 169

Too strong pro-inflammatory response around Sepvp catheter.

Answer 170

Too little immune activation around Pvp-coated polyamide catheter. * Hydrophilic surface * In vitro 75% less bacterial adherence than on PA

Answer 171

Disbalance of pro-/anti-inflammatory cytokines: low IFN-y Macrophage survival and multiplication leading to: 1. Spreading 2. Systemic disease 3. Sepsis

Answer 172

Develope materials which even in presence of micro-organisms: * will allow a proper host immune response capable of clearing the pathogens * will allow proper host tissue responses resulting in infection-free wound healing

Answer 173

* Chemistry of base materials: bio-compatibility, “immune-compatibility” * Surface topographies: host response depending on interaction with surface * Coatings to optimize host response

Answer 174

Release of antimicrobials * Steering the host response: release of inflammatory / anti-inflammatory mediators * SMART release: the right actives at the right time, response to environmental triggers

Answer 175

* Mostly caused by *Staphylococci* * Biofilm formation on the implant * Colonization of the peri-implant tissue

Answer 176

Distinct differences: * Early response due to infection * Later and longer response due to material * Combination leads to strong early response --> immune-dysregulation?

Answer 177

* Anti-apoptosis * Ubiquitylation * Lipid metabolism * Membrane trafficking

Progress Exam 4 (November 12 - 13 - 14 - 15) Flashcards

(208 cards)