Antimicrobial _Lecture 3__Exam 2

... is a long-acting type among all tetracyclines and is used in treatment of ...

Minocycline MRSA - Minocycline is lipid-soluble and gets readily absorbed by prostate and brain cells

What happens when tetracycline interacts with helix 34 at Tet1 site?

tetracycline will inhibit A-site replication; will not allow new tRNA to come tetracycline interferes with proper location of anticodon loop of A-site tRNA. It prevents binding of tRNA to A-site and abolishes peptide chain elongation *inhibits A-site occupation by tRNA*

T/F: all tetracycline binding sites could act synergistically to contribute to the strong bacteriostatic effect of tetracycline

true (tet1 is major mechanism but all sites contribute to strong bacteriostatic effect)

What are the adverse effects of tetracyclines?

GI irritation: N/V, diarrhea Kidney/liver toxicity = rare, usually in pregnant in receiving drug in high doses IV Phototoxic dermatitis = skin inflammation on exposure to sunlight Discoloration of teeth = usually in kids under 7

... is the most commonly used Aminoglycoside

Gentamicin - normally used in combination with Beta-lactam like ampicillin

Tetracyclines are group of broad-spectrum antibiotics that are used to treat ...

Gram+ and Gram- bacteria and some protozoa

Mupirocin is effective against ... bacteria

Gram+, including MRSA

Are tetracyclines bacteriostatic or bactericidal?

bacteriostatic

Based on Davis model, aminoglycosides have been used together with ... as a synergistic treatment since ...

beta lactams beta lactams inhibit cell wall synthesis

Oxytetracycline is the ... spectrum antibiotic that was found near ...

broad Pfizer laboratories in soil sample yielding Streptomyces rimosus Woodward worked out chemical structure of Oxytetracycline enabling Pfizer to mass produce the drug

Doxycycline is a ... spectrum antibiotic used to treat ...

broad, semi-synthetic - chronic prostatitis, sinusitis, syphilis, chlamydia, pelvic inflammatory disease, acne, and rosacea infections - Bacillus anthracis, malaria, Yersinia pestis, plaque, Lyme, Rocky mountain fever, ehrlichiosis derived from studies by Dr. Woodward; Pfizer product Doxycycline can be used to treat other non-infectious diseases

Different classes of aminoglycoside antibiotics form ... with

form additional contacts with rNA; form diff contacts with ribosomal subunit not only RNA but also with proteins - this depends on the drug, its concentration Ex. Kanamycin and Tobramycin

S5, S4 and S12 ribosome proteins contribute to ....

functional formation of decoding site on 30S

Spectinomycin is used to treat ...

gonorrhea caused by Neisseria gonorrhoeae - since many strains are resistant to penicillin and tetracycline

Tet1 binding site is located in the pocket formed by residues of ...

helix 34 and helix 31

Aminoglycosides interact with 50S at ... region

helix 69 region - although aminoglycosides are considered to be classic interactions and inhibitors of 30S subunit, the recent study show that some can also interact with 50S

RRF is needed to ...

separate subunits of ribosome following termination in prokaryotes RRF = ribosomal recycling factor

Tetracyclines inhibit ... ribosomal subunit

small 30S

Spectinomycin binds to ..., but unlike aminoglycosides, ....

small 30S subunit Unlike aminoglycosides, it captures mainly helix34, causing inhibition of translocation during translation - mainly blocks translocation

Aminoglycosides have high affinity for ... within ...

small internal loop within helix 44

15S rRNA is part of ...

small ribosomal subunit

In 10% cases with Cystic Fibrosis, the patients will have premature ...

stop codon, resulting in truncated, nonfunctional CFTR protein CF is genetic, causes progressive disability 10%CF there's mutation in a gene which encodes Cystic Fibrosis transmembrane conductance regulator

The main mechanism of tetracycline action is...

tetracycline captures small ribosomal subunit in H34 and H31 (tet1 site) interaction will be between drug and ribosomal RNA, resulting in inhibition of A site occupation

When cognate aminoacyl-tRNA binds to ribosome, it results in ...

transition from open to close conformation -tRNA is accepted, ribosome changes conformation

T/F: tetracyclines can also bind 30S at the alternative sites

true - bind at alternative sites Tet2-Tet6 that work in synergy with Tet1 binding site

T/F: aminoglycosides and spectinomycin bind to different regions on 16S rRNA and target different steps of translation

true - spectinomycin has diff. mechanism of inhibiting protein synthesis, but this dug can also back maturation/formation of 30S

Why can't Mupirocin be used for long periods of time?

resistance develops

Neomycin, gentamycin and paramomycin block ...

ribosomal recycling

Streptomycin prevents normal dissociation of ...

ribosomes into their subunits, leaving them mainly in 70S form and preventing their re-engagement in translation

The major site of tetracycline binding on 30S is ...

tet1

Aminoglycosides are ... (bactericidal or bacteriostatic) and work on .... bacteria

bactericidal some work on Gram-/Gram+; some only on Gram-

At low concentration, Kanamycin and Tobramycin .... At high concentration, Kanamycin and Tobramycin ...

decreases fidelity of translation form dimers (symmetric and asymmetric), which changes the chemistry of interactions with 30S *dimers cause inhibition of 30S and 50S subunit interaction*, leading to accumulation of dissociated 30S subunits which is lethal to cells

Kanamycin and Tobramycin are prone to ...

dimerization - use error-prone mechanism of inhibition of protein synthesis by capturing small internal loop within helix 44 + form *dimers* Dimers can bind helix 44 in additional sites resulting in inhibition of 50S subunit interaction

How was streptomycin discovered?

during WWII a lot of American soldiers were dying from infections, mostly tuberculosis. Government gave Waksman funds and pathogenic strain of TB to find antibiotic. Graduate student Schatz found bacterial strain that was extremely active against tuberculosis, produce it and bulk and extract substance which later turned out to be streptomycin. *was first antibiotic to be used to treat TB*

T/F: Tetracyclines bind to helix 44 and are A-site occupation inhibitors

false - bind to helix 34 within A-site (Tet1) and prohibit new aminoacyl-tRNA interaction - inhibit A-site occupation

T/F: tetracyclines have high toxicity

false - have low toxicity and minimal side effects

T/F: aminoglycosides are inhibitors of A-site occupation on the 30S subunit

false - it allows tRNA to A site but doesn't allow ribosome to decode properly The idea of decoding is lost (she loves T/F questions)

T/F: there's common structural train among tetracycline binding sites on 30S

false - there's no common structural trail *Tet1 is the major site where tetracycline binds*

T/F: when tetracyclines are bound to the alternative sites tet2 - tet6, they influence the decoding step

false - they disturb new 30S subunit synthesis RNA-binidng proteins S4 and S7 are involved in assembly of 30S during ribosome biogenesis

T/F: tetracyclines don't interact with ribosomal proteins

false interact with r-proteins in the alternative sites Tet2-Tet6 and, therefore, may also influence inhibition of new ribosome assembly (ribosome biogenesis)

Is Mupirocin bacteriostatic or bactericidal?

Bacteriostatic at low concentration Bactericidal at high concentration

How are tetracyclines administered?

- absorbed by GI and therefore given orally Usually given orally Most of them can be chelated with ions like Al+++, Ca++, Mg++. When tetracycline is chelated, it'll pass through intestine without being absorbed. Doxycyline overcomes this problem; it's structure doesn't allow for it to be chelated and therefore it's better absorbed with food Tetracyclines, other than doxycycline, shouldn't be taken with milk

What is the structure of aminoglycosides?

- amino modified sugars (Gentamicin has 3 molecules of sugar) Strongly polar, +charged due to amino groups highly soluble in water, insoluble in lipids enhanced activity in alkaline environment can't be absorbed via GI so usually given as IV poorly penetrate blood-brain barrier since +charged interact with multiple -charged molecules inside the cell (lipopolysaccharides of bacterial wall, phospholipids, RNA)

What 3 mechanisms have beed discovered how Minocycline and Doxycycline can be used in treating non-infectious diseases?

- can act as inhibitors of Matrix Metalloproteinases, which are enzymes that control tissue remodeling, tumor invasion, inflammation (by suppressing these enzymes ex. tumor won't be as invasive as without treatment) - scavenging reactive oxygen species (side effect of ETC in mitochondria) Superoxide, peroxide and hydroxide radicals can damage cellular structures, DNA/RNA leading to mutations - suppress apoptosis by mediating inhibition of caspases expression and stabilization of mitochondria

What is the clinical use of Tetracyclines?

- enter Gram- bacteria via passive diffusion through porin proteins in the outer membrane, followed by E-dependent transport across inner cytoplasmic membrane - enter Gram+ via E-dependent transport (mammalian cells lack this transport system; that's why tetracyclines due to their way of entry are bacteria specific)

What is the main target for the majority of aminoglycosides?

- form H bonds and salt bridges with Adenine in position 1408 and Guanine in 1491. This forces ribosome to change conformation no matter what and accept any tRNA that comes

What are the adverse affects of spectinomycin?

- infrequent and minor - itching, chills, stomach-ache, red rash

Mechanisms by which aminoglycosides can inhibit protein synthesis

- interact with ribosomes (- charged RNA) to block protein synthesis - besides acting on small subunit, can also form contacts with large ribosomal subunit *don't inhibit protein synthesis per say, but they make ribosome function with very low fidelity* They promote error-prone synthesis of proteins and that results in formation of heavily mutated cellular proteons that makes cell not function normally. As result, cell arrests in growth, division and eventually dies There are additional mechanisms of aminoglycosides function: - inhibition of early stage of translation initiation (streptomycin) - can inhibit formation of 70S complex -> joining of large and small ribosomal subunit (late step of translation initiation) - can inhibit dissociation of 70S (when translation is done and subunits of ribosome need to dissociate to participate in new round of translation) - inhibition of recycling step (dissociation of 70S and recharging cell with a new free subunits for another round of translation)

What is the concentration-dependent effect with aminoglycosides?

- same antibiotic uses diff. mechanism of ribosome inhibition depending on drug concentration Ex. Kanamycin and Tobramycin form dimers at high concentration Gentamicin, neomycin and paramomycin saturate helix 44 at high concatenation and then move to helix 69 - not only inhibit protein synthesis by making ribosome incapable to correct decoding, but also completely block translation if present in high concentration. This happens due to alternative binding sites like H69.

In general, aminoglycosides form multiple contacts with ... But some representatives of aminoglycosides can also form additional bonds with ...

16S rRNA of small ribosomal subunit 30S at the decoding site (= A site), specifically in the small internal loop within helix 44 other parts of 30S and 50S

Structure of tetracyclines

-4 hydrocarbon rings with different modifications that give them different properties - all the drugs on pic are used to treat infectious diseases, but some of them are used to treat non-infectious diseases Doxycycline is used to treat Lyme disease (don't need to know structures)

What is the mechanism of resistance to aminoglycosides?

1- deactivation of glucose molecules by N-acetylation, adenylation or O-phosphorylation Aminoglycosides can be modified by bacterial enzymes by addition of acetyl-, phosphoryl- or -adenyl groups and drug will stop functioning as it's supposed to 2- reduced intracellular drug concentration due to change in outer membrane permeability or active efflux of the drug 3- alteration of amino glycoside binding site on 16S rRNA via modification (methylation of small internal loop of H44, Adenine 1408 resulting in drug not being able to interact with A1408) or mutation

What are the adverse effects of aminoglycosides?

1. Ototoxicity -> can inhibit mitochondrial ribosomes - drug accumulates in endolymph and perilymph of inner ear and can damage hair cells s/s: loss of balance, ear ringing, head spinning; hearing loss is usually irreversible If prescribed in small dose and pt is watched closely, usually in 3 doses you can know how the dug works in this patient 2. Renal toxicity -> aminoglycosides accumulate in proximal tubule - creatinine and BUN need to be monitored 3. Neuromuscular blockage => rare; aminoglycosides compete with Ca++ at presynaptic sites and lead to reduced release of Ach - failure to depolarize, paralysis s/s: inability to move, breathe; this is rare side effect Aminoglycosides in small doses and in combination with other drugs can be safe

4 major resistance mechanisms of tetracyclines

1. enzymes either involved in exporting drug out (efflux pumps) or not letting it enter cell 2. enzymes inactivate drug 3. some bacterial strains have Ribosomal protection proteins (TetM, TetO, TetS), which show homology to translational factors EF-Tu and EF-G EF-Tu is capable of interacting with A site. Bacterial TetM can mimic EF-Tu and bind A site on 30S when tetracycline is there. It can then hydrolyze GTP and this E will be enough to release tetracycline out of A site 4. mutation in 16S rRNA in Tet1 binding site, which leads to conformational changes in 30S and results in inability of Tet1 to interact with the drug

What is the function of small internal loop within helix 44?

2D structure: H bonds between complimentary regions on rRNA molecule - formation of H bonds results in appearance of multiple hairpins and loops 2D structure gets assembled into 3D structure Different regions of 2D structure interact with each other via different non-covalent interactions (static, Van-der-Waals and others) forming A, P and E sites Scientists divided each part of 16S rRNA into different regions for simplicity Aminoglycosides capture small internal loop within helix 44 - *this region monitors conformational change of ribosome when process of decoding occurs*

Aminoglycosides, Tetracyclines, Spectinomycin target ... ribosomal subunit

30 S

Dimers formed due to Kanamycin and Tobramycin cause inhibition of ... leading to accumulation of ....

30S and 50S subunit interaction dissociated 30S subunits which is lethal to cells

Aminoacyl-tRNA synthetases function

= aminoacetylation of tRNA = catalyze covalent attachment of AA to tRNA tRNA has anticodon loop (secondary structure looks like a clover leaf) Enzyme has 3 major regions: (pic has 3 ovals) - AA interaction - tRNA interaction (tRNA anticodon will correspond to codon) - Active site *reaction is between Adenine and -COOH on AA *reaction requires ATP* because ATP is physically participating in reaction, not because reaction is E dependent *aminoacetylated tRNA (charged tRNA) will dissociate and go to participate in translation

Aminoglycosides target ... site within bacterial ... rRNA of .... subunit

A-site 16S rRNA 30S subunit Since Aminoglycosides are +, they have tendency to react with -charged molecules like RNA, phospholipids

Just like tetracyclines, tigecycline is an inhibitor of ...

A-site occupation *targets ribosome at Tet1 site

Tetracycline captures ...., which are 2 bases that stick out from the sugar-phosphate backbone of H34 and this interaction is coordinated by ....

Adenine 1196 and Cytosine 1064 Mg++ __________________________ Adenine1196 and Cytosine1064 are pointing out of H34 towards A site and form a camp which holds tetracycline molecule by hydrophobic interactions Interaction with H34 affects ribosomal translocation step of translation Most of ribosomal structures are coordinated by Mg++

Streptomycin has a little diff. structure from the rest of aminoglycosides. How does it differ?

Aminoglycosides have 3 sugars modified with amino groups, which give the drug +charge. Strepromycin has streptidine backbone attached to 2 sugar molecules - interacts with small ribosomal subunit 30S close to helix 44 and *will form contacts not with RNA but with protein*

The first Tetracycline discovered was ...

Chlortetracycline - found in Streptomyces aureofaciens (soil bacteria) - used to treat conjunctivitis in cats

How does ribosome decode RNA information?

Codon is present at A site New tRNA comes and has anti-codon sequence Anti-Codon sequence aligns with codon sequence H bonds begin to form (wobble position isn't really important. tRNA is called cognate tRNA because it will carry the same AA; each AA can be encoded by multiple codons. If tRNA has a mismatch in 1st or 2nd position, it'll be rejected. Acceptance of tRNA occurs by small ribosomal subunit, helix 44 region. When tRNA with correct AA comes, small internal loop of helix 44 will change confirmation in such a way that A site becomes closed conformation and tRNA will be accepted so that it cannot dissociate from ribosome. If tRNA is non-cognate (has wrong AA), the region will not change conformation and ribosome will stay as is and tRNA will dissociate. Aminoglycosides interact with this region and will promote it to change conformation regardless which tRNA comes. Any random tRNA that comes will be accepted and that's how mutated proteins form.

... is a tetracycline used in treatment of Lyme, acne and bronchitis

Demeclocycline - resistance to demeclocycline is gradually becoming more common and is now rarely used for infections

... is used to treat hyponatremia due to SIADH

Demeclocycline SIADH is mostly found in patients with small cell carcinoma of the lung, pneumonia, brain tumors, head trauma, strokes, meningitis, encephalitis - excessive release of ADH (vasopressin) leads to fluid overload - *Demeclocycline induces dehydration due to inability to concentrate urine* Dehydration is a side-effect of Demeclocycline

The most popular tetracycline used today is ...

Doxycycline

Binding of amino glycoside to H69 occurs when ...

H44 is already saturated binding of drug suppresses RRF-induced conformational changes in H69 ---- When there's no gentamicin in presence of RRF, H69 is shifted towards RRF. In presence of gentamicin, neomycin or paramomycin, the drug will not allow Helix 69 to move away from 30S and will inhibit subunit dissociation (aminoglycosides have high affinity for H44; so when H44 is saturated and there's still drug in the system, then aminoglycoside will interact with H69. When drug binds to H69, it suppresses RRF-induced conformational changes and therefore inhibits dissociation of ribosome

Mupirocin (Bactrim) inhibits ...

Isoleucine-tRNA-synthetase (one of the 20 aminoacyl tRNA synthetases)

Which tetracycline has a possible neuroprotective and anti-inflammatory effects against progression of a group of neurodegenerative disorders including MS, RA (rheumatoid arthritis), amyotrophic lateral sclerosis (ALS), Huntington's and Parkinson's?

Minocycline

Which tetracyclines are currently in a clinical trial to treat non-infectious diseases?

Minocycline and Doxycycline

... is currently the only clinically available Aminoacyl-tRNA-synthetase (ARS)

Mupirocin (=Bactrim)

Which animo glycosides interact with 50S subunit?

Neomycin Gentamycin Paramomycin - at helix 69 region Large and small subunit interact with each other via electrostatic contacts and salt bridges Helix 69 is involved in formation of contact with 30S. Helix 69 is a dynamic structure and moves back and forth 8 amstrong. If it moves away from 30S, the subunits will dissociate. If it moves closer, the subunits will associate. RRF (ribosomal recycling factor) dictates how Helix 69 moves. When translation terminates, RRF comes and dissociates the whole 70S complex. Helix 69 has high affinity for RRF and it'll be shifted 8A, break contact with 30S and subunits will dissociate.

Streptomycin shows additional contacts with the 30S subunit protein ...

S12 S12 is critical component of Asite of 30S subunit Within S12, Lysine 42forms multiple major contacts with streptomycin If Lys42 is mutated (for ex. to Ala), the contacts will be lost S12, similarly to helix 44, contributes to ribosome geometry, causing formation of closed structure of 30S upon binding of a cognate aminoacyl-tRNA Even if Streptomycin interacts with diff. part of ribosomal 30S and forms major contacts with S12, it still causes the same end result -> make ribosome lose its ability to decode because ribosome will form closed conformation regardless of which tRNA comes

What is the mechanism of action of spectinomycin?

Spectinomycin, similarly to aminoglycosides, binds to 16S rRNA of 30S but in a different region -> in Helix 34 (aminoglycosides capture small internal loop in helix 44) - binds to helix34 in 16S rRNA and makes H-bonds to a number of nucleotides Most interactions are with Guanine1064 and Cytosine1192 - Similarly to some aminoglycosides, Spectinomycin is able to capture and interact with *r-protein S5* Not yet proven, but hypothesis that Lysine25 in protein S5 approaches spectinomycin and interacts with it. *S5, S4 and S12 ribosome proteins contribute to functional formation of decoding site on 30S*

What happens in the first and second step of tRNA aminoacylation reaction?

Step 1: aminoacyl adenylate intermediate forms, which is Aminoacyl bound to Adenine on AMP (2 phosphates are released) - dot represents association with enzyme Step 2: covalent bond is transferred from Adenine of AMP to Adenine of tRNA forming aminoacetylated tRNA

... is the oldest antibiotic in Aminoglycosides family

Streptomycin - not really used today since 1943 most bugs are resistant to it (don't memorize) Neomycin only used topically Netilmicin = for preop coverage before GI surgery

The inhibitory action of tetracycline is mainly assigned to ... site

Tet1

... is the only representative of new class of tetracycline-based antibiotics glycyclines

Tigecycline Glycyclines are subfamily of tetracyclines and has only 1 representative

... is an aminoglycoside used against Pseudomonas aeruginosa

Tobramycin - Pseudomonas thrives on most flat surfaces; resists sterilization - Amikacin has broader spectrum of activity and like Tobramycin is good for hospital-acute infections, but many bugs develop resistance to it

T/F: tetracycline has one primary and multiple secondary sites of binding within 30S

True Tetracyclines have multiple interaction sites: Tet1 - Tet6 - these 6 sites were identified during crystallographic analysis Aminoglycosides have at least 2 major sites of interaction with 30S => H44 and H69 (H69 is actually not part of the small subunit)

Spectinomycin is an aminocyclitol antibiotic, closely related to the ... and is produced by the bacterium ...

aminoglycosides Streptomyces spectabilis - similar to aminoglycosides

What is the mechanism of action of spectinomycin?

by interacting with H34, the drug inhibits translocation of tRNA during translation. Translocation is when tRNA from one site moves to next through series of large conformational changes in ribosome, including movements of certain elements of 30S subunit. These movements involve H34. By interacting with this region, H34 cannot be flexible or do rearrangements on conformation and blocks ribosomal ability to move 1 codon (=3 nucleotides) toward 3' on mRNA Spectinomycin binds to H34 and sterically blocks movement of ribosome; prevents changes in conformation of H34 and therefore freezes ribosome and doesn't allow tRNA movement

What is the mode of administration of aminoglycosides?

cannot be given orally since minimally absorbed in GI given IV or IM - poorly penetrate bacterial membrane, but small amount of them that pass through bacterial membrane will affect ribosomal fidelity and heavily mutated proteins will be generated. Some of these proteins will be inserted in the membrane causing formation of membrane pores and increasing drug influx = DAVIS model

In what way do Kanamycin and Tobramycin inhibit the last step of initiation step of translation?

inhibition of 70S formation via ability of these antibiotics to dimerize __________________ Inhibition of initiation -> last step of initiation step of translation: - small subunit, which in the complex with initiation factor 3 and initiation factor 2, will interact with mRNA. AUG start codon will be placed in P site and small subunit is in the complex with fMet containing tRNA (has UAC as anticodon) The complex assembles. Interaction with initiation factor 2 (IF-2) hydrolyzes GTP and E is used to change conformation This results in ability of 30S initiation complex to interact with large ribosomal subunit. *this step is irreversible* and will result in formation of 70S initiation complex Irreversible means that from this point on ribosome is committed to transition and protein will be made Dimers of Kanamycin and Tobramycin can capture additional parts within helix 44 and will inhibit association of 30S complex with 50S. 30S will be dissociated and translation will be arrested (bacteria won't be able to make protein and will eventually die)

S12 of 30S is involved in ...

initiation of protein synthesis

Streptomycin has been shown to prevent ... by ...

initiation of protein synthesis by blocking of initiation N-formylmethionine tRNA to the ribosome

Besides Streptomycin being involved in error-prone mechanism of protein synthesis, it's also able to inhibit ...

initiation stage of II of translation - In initiation II stage mRNA, start codon is placed in P site, IF-1 occupies A site (initiation factor); IF-3 binds to ribosome to prevent mature interaction with large ribosomal subunit. In the next step, IF-2 brings first tRNA with UAC anticodon charged with fMet. fMet is placed at P site and U will form 2 H-bonds with A, A will form 2 Bonds with U, C will from 3 H-bonds with G. This is formation of 30S initiation complex. Streptomycin blocks formation of these interactions so that fMet can't come and can't interact with ribosomal subunit (streptomycin has this additional mechanism)

Alternative mechanism of tetracycline action is ...

interaction via multiple alternative sites, leading to inhibition of ribosome biogenesis

Currently Aminoglycosides are being tested on Cystic Fibrosis cell cultures. Their proposed method of action is ...

make ribosome translate by adding aminoglycoside; it'll skip stop codon and keep translating CFTR protein will still be generated with mutations, but certain amount of this protein will have mutations probably not in the critical domain and may be enough to recover function of the gene - gentamicin has been used to skip premature codon

When near-cognate aminoacyl-tRNA binds to ribosome, 30S remains in ...

open conformation (similar to when decoding center remains unoccupied) - open conformation of 30S allows for it dissociation from the decoding center tRNA is rejected, ribosome doesn't change conformation Aminoglucoside will force the ribosome to change conformation by binding the flexible region A1492 and A1493

T/F: every member of amino glycoside class of antibiotics induces unique changes within the whole ribosome and causes different defects in translation

true - can affect different steps of translation initiation (early initiation -> formation of 30S initiation complex; late initiation -> formation of 70S complex) - can affect elongation of translation -> ribosome won't decode with good fidelity - affects ribosome recycling using 2 mechanisms: one mechanism isn't well understood, but the other mechanism involves interaction with H69

T/F: tetracyclines interact with ribosomal proteins

true - doesn't only involve interactions with RNA, but involves interactions with four ribosomal proteins S4 protein -> tet2 S7 -> tet6 S9 -> tet4 S17 -> tet5 Ribosomal proteins have globular structure and long tail. S4 and S7 are involved in initiation of assembly of 30S Just know from this slide that tetracycline interacts with ribosomal proteins

T/F: besides being strong anti-microbial agents, tetracyclines demonstrated activity in treatment of non-infectious human diseases

true - neurodegenerative diseases and others

T/F: Aminoglycosides induce error-prone synthesis of proteins

true of all aminoglycosides (some also have other actions)

Mupirocin is used to treat ...

used as topical tx for bacterial skin infections (furuncle, skin ulcers, open wounds etc) MRSA *unstable in blood (inactivated by plasma) *topical