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Mechanisms of Antibiotics Resistance

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What is the primary origin of antibiotics?

Soil bacteria and fungi

What is the primary concern with antibiotic resistance?

Difficulty in treating infections

Which bacterial strain's resistance to penicillin is an example of antibiotic resistance?

Streptococcus pneumoniae

What was the first antibiotic discovered?

Penicillin

What is the outcome of antibiotic resistance among bacterial pathogens?

Infections are harder to treat

What is the result of the development of thousands of antibiotic variants and analogues?

Varying effects on different infectious organisms and less toxicity to humans

What is the primary function of efflux pumps in bacterial cells?

To remove noxious compounds from the cytoplasm

Which of the following efflux pump systems is responsible for multiple antibiotics and toxic compounds in Neisseria gonorrhoeae?

MtrCDE system

What is the energy source used by efflux pumps to transport substrates?

Proton motive force (PMF)

Which of the following is a characteristic of the NorA pump in Staphylococcus aureus?

It provides resistance to a range of structurally unrelated antibiotics

What is the role of the periplasmic protein in efflux pumps?

To connect the efflux pump to the outer membrane protein

What is the result of the overexpression of an efflux pump gene in a bacterium?

A multiple antibiotic resistance phenotype

Which of the following is a mechanism of action of efflux pump systems?

Catalyzing the active transport of substrates

What is the role of the outer membrane protein in efflux pumps?

To form a channel through the periplasm and outer membrane

How many families of efflux pumps have been described in microorganisms?

Five

What is the function of the MtrR protein in Neisseria gonorrhoeae?

To repress the expression of MtrCDE

What is the main reason why efflux is undesirable for organisms trying to treat infections?

It prevents the effective concentration of antibiotics at the site of infection

What is the primary function of beta-lactamase enzymes produced by bacteria?

To break the beta-lactam ring of antibiotics

What is the result of the action of erythromycin esterase (EreA) on macrolide antibiotics?

Hydrolytic cleavage of the lactone ring

What is the difference between the Mpr strain and wild-type bacteria in terms of macrolide lincosamide and streptogramin B MLS antibiotics?

The Mpr strain has a point mutation that prevents MLS antibiotic binding

What is the result of the modification of target enzymes by antibiotic-inactivating enzymes such as erythromycin esterases and β-lactamases?

Decreased antibiotic binding affinity

What is the function of transpeptidase enzymes in relation to penicillin-like antibiotics?

To catalyze the acetylation of the antibiotic

What is the reason why Flucloxacillin, a penicillin, was no longer effective against staphylococci?

It was inactivated by staphylococcal penicillinase

What is the effect of enzymatic inactivation on antibiotics?

It makes antibiotics less effective

What is the reason why MRSA super bacteria are resistant to penicillin-like antibiotics?

They have a low affinity for the B-lactam ring in penicillin

What is the primary mechanism of resistance in Kmr bacteria against aminoglycoside antibiotics?

Phosphotransferase enzyme that inactivates aminoglycosides

How does erythromycin resistant methylase prevent antibiotic binding?

By methylating the ribosomal target site

What is the typical mechanism of high-level resistance to vancomycin in Enterococcus faecium?

Stepwise acetylation of cell wall precursors

What is the role of biofilm formation in antibiotic resistance?

It renders antibiotics ineffective due to phenotypic changes

What is the effect of aminoglycoside modifying enzymes on the antibiotic's ability to bind to the 30S subunit?

It decreases the antibiotic's affinity

What is the mechanism of resistance in Enterococci against aminoglycosides?

Presence of aminoglycoside modifying enzymes

What is the typical outcome of infection by vanA-containing isolates in Enterococcus faecium?

Treatment failure with vancomycin

How does the acquisition of resistance genes contribute to biofilm resistance?

It provides high levels of drug tolerance

What is the effect of high-affinity mechanisms on aminoglycoside uptake in P. aeruginosa biofilms?

It inhibits aminoglycoside uptake

What is the mechanism of chloramphenicol inactivation by R-Plasmids?

Chloramphenicol acetyltransferase

What is the primary reason for the inefficiency of antibiotics in penetrating biofilms?

Physicochemical interactions between the drug and the matrix

What is the consequence of stepwise selection processes involving multiple genetic mutations in bacteria?

Bacteria become highly resistant to specific antibiotics while maintaining a level of resistance

What is the relationship between biofilm organisms and the incidence of complete infection removal?

The proximity of resistance in biofilm organisms results in a lower incidence of complete infection removal

What is the primary reason for the ineffective treatment of biofilm-related infections?

Impaired penetration of antibiotics into the biofilm

What is the estimated cost of device-related infections in the USA?

Over $3 billion per year

What is the primary mechanism of antibiotic resistance in biofilms?

Sequestration of antibiotics by the extracellular matrix

What is the characteristic of biofilm cells that contributes to antibiotic tolerance?

Close-knit packing and slow growth due to nutrient limitation

What is the function of efflux pumps in bacterial cells?

To recognize and transport antibiotics out of the cell

What is the energy source used by efflux pumps to transport antibiotics?

ATP

What is the primary function of the AcrAB-TolC efflux system in E. coli?

To recognize and expel various substrates

What is the main mechanism of antibiotic resistance conferred by the QacA multidrug efflux pump in Staphylococcus?

Efflux of organic cationic compounds

How does the SatAB efflux system in E. faecium contribute to high-level antibiotic resistance?

By both reducing drug uptake and effluxing antibiotics

What is the mechanism of ribosomal protection in Bacillus?

Transfer of an ATP-binding ribosomal protein and phosphorylation of a hydrolytic enzyme

How does the production of an alternative PBP with low affinity for beta-lactam compounds contribute to methicillin resistance?

By preventing amoxicillin from binding its target PBPs

What is the function of the carbapenemase enzymes produced by certain Enterobacteriaceae?

To hydrolyze carbapenems to inactive metabolites

What is the characteristic of the single drug/MF superfamily of efflux pumps?

Recognition of multiple unrelated drugs

What is the role of the ATP-binding ribosomal protein in Bacillus?

To confer resistance to macrolides, lincosamines, and streptogramin B

What is the consequence of dysfunctional AcrAB-TolC systems in E. coli?

Lower resistance to fluoroquinolones and inhibitor Phe-Arg β-naphthylamide

What is the characteristic of the efflux systems used by bacteria to remove toxic substances and drugs?

Similarity to those in higher organisms

What is one of the negative outcomes of antibiotic resistance mentioned in the text?

Permanent hearing loss in patients with pneumococcal meningitis

What was the first antibiotic discovered, but its efficacy was not realized until a specific event?

Penicillin

Which genetic mechanism of antimicrobial resistance involves acquiring genes from another microorganism?

Horizontal gene transfer

What is the main reason behind the increased medical costs associated with antibiotic resistance?

Prolonged treatment durations

Which type of antibiotics may alter the microbial ecology of the human body?

Broad-spectrum antibiotics

What percentage of hospital admissions is attributed to adverse effects of antibiotic therapy?

10%

What natural process has been influenced by human activity and has led to the proliferation of antimicrobial resistance?

Hybrid gene transfer

Which event caused infectious diseases to not be eradicated as predicted by U.S. surgeons?

Misuse and overuse of antibiotics

What change in a bacterium's DNA sequence can provide it with a selective advantage against antibiotics?

Mutation

What impact has the unrestricted use of newer antibiotics had according to the text?

Economic consequences

What is the key difference between transduction and conjugation in bacteria?

Transduction involves genes being transferred through bacteriophages, while conjugation involves genes being transferred through pili.

How do bacteria become resistant to harmful substances at low frequencies?

By changing shape in just 20 minutes due to anamorphosis.

What is the role of penicillinase in bacteria resistance?

It breaks down the -lactam vibratory of antibacterial drugs.

How are efflux pump systems described in bacteria resistance to antibiotics?

They are chromosome-encoded elements that expel antibiotics from the cell.

What initiates recombination during horizontal gene transfer between bacteria?

Physical contact between two bacteria of compatible mating types.

How do efflux pump systems provide resistance to antibiotics in bacterial cells?

By expelling several structurally unrelated antibiotics from the cell.

What do efflux pump systems need for energization to resist antibiotics in bacterial cells?

Proton motive force.

What can happen if the efflux pump systems in bacteria are overexpressed?

It is often associated with mutations in repressor genes.

How does DNA-mediated transformation differ from recombination during horizontal gene transfer between bacteria?

DNA-mediated transformation involves transferring naked DNA from one bacterium to another.

Why is the study of efflux pump systems crucial for the continued effectiveness of antibiotics?

Understanding them can help develop efflux pump inhibitors to potentiate antibiotics.

What is the primary consequence of antibiotic resistance among bacterial pathogens?

Increased difficulty in treating infections

What is the main outcome of the discovery of antibiotics?

Major breakthrough in human health history

Which type of bacteria are antibiotics effective against?

Gram-positive bacteria

What is the reason behind the varying effects of antibiotics on different infectious organisms?

The development of thousands of variants and analogues

What is the result of the evolution of bacteria to be resistant to most or all available antibiotics?

Infections becoming harder to treat and increasing the likelihood of spreading to others

What is the example of antibiotic resistance mentioned in the text?

Streptococcus pneumoniae's resistance to penicillin

What is the main consequence of the misuse and overuse of antibiotics?

The evolution of antibiotic-resistant bacteria

What is the primary function of antibiotics?

To inhibit the growth of bacteria

What is the result of the emergence of antibiotic-resistant bacteria in hospitals?

Increased medical costs

What is the significance of studying antibiotic resistance?

To address the negative consequences of antibiotic therapy

What is the main mechanism of antibiotic resistance?

Mutation and gene transfer

What is the consequence of the unrestricted use of newer antibiotics?

Economic consequences

What is the impact of antibiotic resistance on the treatment of pneumococcal meningitis?

Increased treatment failures

What is the natural process that has been influenced by human activity and has led to the proliferation of antimicrobial resistance?

Horizontal gene transfer

What is the result of the overuse of penicillin for streptococcal pneumonia treatment?

The emergence of antibiotic-resistant bacteria

What is the consequence of antibiotic resistance on the natural history of diseases?

The creation of new problems

What is the primary mechanism of horizontal gene transfer between bacteria that involves the exchange of genetic material through direct cell-to-cell contact?

Recombination

What is the primary function of the enzyme penicillinase produced by some bacteria?

To break down the lactam ring of antibacterial drugs

What is the characteristic of efflux pump systems that allows them to expel multiple structurally unrelated antibiotics from the cell?

Broad substrate specificity

What is the primary mechanism of genetic change that increases the effectiveness of antibiotics against bacteria?

Genetic mutation that causes the bacteria to attack the agent

What is the primary role of plasmid transfer in horizontal gene transfer?

To transfer genetic material through a mobile genetic element

What is the primary mechanism of antibiotic resistance conferred by efflux pump systems?

Expelling the antibiotic from the cell

What is the primary mechanism of action of DNA-mediated transformation in horizontal gene transfer?

Transferring genetic material through naked DNA

What is the primary reason why efflux pump systems are a major concern in the development of antibiotics?

They can lead to multidrug resistance

What is the primary mechanism of genetic change that allows bacteria to become resistant to harmful substances at low frequencies?

Anamorphosis and change in shape

What is the primary mechanism of recombination in horizontal gene transfer?

Transferring genetic material through direct cell-to-cell contact

What is the primary function of the periplasmic protein or adaptor in efflux pumps?

To connect the efflux pump to the outer membrane protein

Which of the following efflux pump systems is responsible for the transport of tetracycline out of bacterial cells?

TetA system

What is the result of the overexpression of an efflux pump gene in a bacterium?

Multiple antibiotic resistance phenotype

What is the energy source used by efflux pumps to transport substrates?

Proton motive force (PMF)

Which of the following is a characteristic of the RND efflux pump system?

It spans both the inner and outer membranes of the bacteria

What is the primary function of efflux pumps in bacterial cells?

To maintain a less toxic intracellular environment

Which of the following is an example of an efflux pump system that is responsible for multiple antibiotics and toxic compounds?

MtrCDE system

What is the role of the MtrR protein in Neisseria gonorrhoeae?

To regulate the expression of the MtrCDE operon

Which of the following efflux pump systems is responsible for the removal of quinolones, hydrophilic β-lactams, erythromycin, and tetracycline from Staphylococcus aureus?

NorA system

What is the consequence of the overexpression of an efflux pump gene or alteration to the pump or its regulators in a bacterium?

Multiple antibiotic resistance phenotype

What is the primary mechanism of resistance to macrolide antibiotics in Gram-positive and Gram-negative species?

Action of erythromycin esterase (EreA) catalyzing the hydrolytic cleavage of the lactone ring

What is the target of beta-lactamase enzymes produced by bacteria?

The beta-lactam ring of penicillins, cephalosporins, and carbapenems

What is the result of the modification of target enzymes by antibiotic-inactivating enzymes such as erythromycin esterases and β-lactamases?

A weak positive selection process under antibiotic conditions

What is the primary function of clavulanic acid in the treatment of bacterial infections?

To inhibit the action of beta-lactamase enzymes

What is the characteristic of the Mpr strain in terms of macrolide lincosamide and streptogramin B MLS antibiotics?

It has a point mutation that prevents MLS antibiotic binding

What is the primary mechanism of enzymatic inactivation of antibiotics?

Enzymatic modification of the antibiotic structure

What is the primary reason for the development of antibiotic resistance in bacteria?

To survive in the presence of antibiotics

What is the role of transpeptidase enzymes in bacterial resistance to penicillin-like antibiotics?

To split the complex before acetylating the antibiotic

What is the primary mechanism of antibiotic resistance conferred by the Erm genes?

Erythromycin ribosome methylation

What is the primary reason for the persistence of infections in biofilms?

The impaired penetration of antibiotics

What is the result of the stepwise selection process involving multiple genetic mutations in bacteria?

The maintenance of a level of resistance to specific antibiotics

What is the primary mechanism of antibiotic resistance in biofilms?

The sequestration of antibiotics by the extracellular matrix

What is the significance of the rifampicin gene in antibiotic resistance?

It results in strains having only planktonic or biofilm resistance to rifampicin

What is the characteristic of biofilm cells that contributes to antibiotic tolerance?

Slow growth rate due to nutrient limitation

What is the energy source used by efflux pumps to transport antibiotics?

ATP

What is the significance of the polysaccharide intercellular adhesion in staphylococcal biofilms?

It acts as a barrier to antimicrobial agents

What is the consequence of the selection of inappropriate antibiotics in treating biofilm infections?

The increased resistance of bacteria to antibiotics

What is the estimated cost of device-related infections in the USA?

Over $3 billion per year

What is the primary reason for the high antibiotic dose strategies being less preferred in treating biofilm infections?

The increased risk of side effects and drug toxicity

What is the characteristic of the single drug/MF superfamily of efflux pumps in bacteria?

They can confer resistance to several unrelated drugs due to their varying size, charge, and chemical composition.

Which of the following efflux pumps is capable of recognizing and expelling various substrates, including quaternary ammonium compounds, antiseptics, and dyes?

QacA

What is the mechanism of methicillin resistance in MRSA isolates and S. pneumoniae isolates?

Production of an alternative PBP with low affinity for beta-lactam compounds.

Which of the following is NOT a characteristic of the AcrAB efflux system in E. coli?

It is plasmid-mediated and can be transferred between bacterial species.

What is the mechanism of antibiotic resistance in Bacillus through ribosomal protection?

Transfer of an ATP-binding ribosomal protein and phosphorylation of a hydrolytic enzyme.

What is the consequence of dysfunctional AcrAB-TolC systems in E. coli?

Decreased resistance to fluoroquinolones and inhibitor Phe-Arg β-naphthylamide.

What is the function of the carbapenemase enzymes produced by certain Enterobacteriaceae?

To hydrolyze carbapenems to inactive metabolites.

Which of the following efflux pumps is responsible for high-level resistance to many antibiotics in E. faecium?

SatAB

What is the energy source used by efflux pumps to transport substrates across the cellular membrane?

Either ATP or a chemiosmotic gradient

What is the result of antibiotic modification by antibiotic-inactivating enzymes such as beta-lactamases?

Prevention of antibiotic binding to the target enzyme.

What is a common mechanism used by bacteria to resist antibiotics by making them ineffective in targeting the ribosome?

Ribosomal protection

Which enzyme produced by some bacteria catalyzes the methylation of the ribosomal target site of erythromycin, leading to antibiotic resistance?

Erythromycin resistant methylase

What leads to reduced affinity and bactericidal activity of aminoglycosides in bacteria?

Ribosomal protection

In which case does a specific microbial mechanism inhibit aminoglycoside uptake in P. aeruginosa biofilms?

Iron-transport system downregulation

Which modification alters the binding site of fosfomycin, rendering it ineffective against bacteria?

UDP-N-acetylglucosamine enolpyruvyl transferase modification

What is a common strategy employed by bacteria to decrease the binding affinity of antibiotics to the ribosome?

Ribosomal protection

Which enzyme is responsible for the inactivation of chloramphenicol in R-Plasmids and the antibiotic itself?

Chloramphenicol acetyltransferase

What is a mechanism that bacteria use to resist antibiotics by altering the cell wall precursor, usually leading to low-level resistance?

Cell wall precursor alteration

Which bacterial resistance mechanism involves stepwise acetylation of cell wall precursors by enzymes encoded by van genes?

Biofilm formation

What is the primary action of aminoglycoside modifying enzymes in bacteria that reduce antibiotic effectiveness?

30S subunit binding inhibition

Explore the mechanisms of antibiotics resistance in bacteria and how it impacts human, animal, and plant health. Learn about the discovery of antibiotics, their effectiveness against gram-positive bacteria, and the challenges posed by antibiotic resistance.

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