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Cross-resistance Wiki2Web Clarity Challenge

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Study Guide: Mechanisms of Drug Resistance: Cross-Resistance and Collateral Sensitivity

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Mechanisms of Drug Resistance: Cross-Resistance and Collateral Sensitivity Study Guide

Defining Cross-Resistance

Cross-resistance is characterized by an organism developing resistance to multiple substances that operate through distinct and unrelated mechanisms of action.

Answer: False

Explanation: Cross-resistance is defined by resistance to multiple substances that share a similar mechanism of action, not distinct and unrelated ones.

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An efflux pump is a common mechanism of cross-resistance because it can actively transport various toxic substances out of a cell, maintaining low internal concentrations.

Answer: True

Explanation: Efflux pumps are a common mechanism of cross-resistance, as a single pump can expel multiple structurally diverse compounds, thereby reducing their intracellular concentration.

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For microorganisms, cross-resistance is defined as a virus's resistance to a new drug due to prior exposure to the exact same drug.

Answer: False

Explanation: Cross-resistance in microorganisms is defined as resistance to a *new* drug as a consequence of prior exposure to a *different* drug, or more broadly, resistance to multiple distinct antimicrobial agents resulting from a single molecular mechanism.

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Structural similarity between compounds is a strong and reliable predictor of cross-resistance, especially when considering aminoglycosides.

Answer: False

Explanation: Structural similarity is generally a weak predictor of cross-resistance, and its predictive power diminishes further when aminoglycosides are excluded from consideration.

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The most common cause of cross-resistance is target similarity, where antimicrobial agents share the same biological target or pathway.

Answer: True

Explanation: Target similarity, where different agents affect the same biological target or pathway, is identified as the most common underlying cause of cross-resistance.

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What is the defining characteristic of cross-resistance?

Answer: Resistance to multiple substances that share a similar mechanism of action.

Explanation: Cross-resistance is fundamentally defined by an organism developing resistance to multiple substances that operate through a similar, shared mechanism of action.

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Which of the following is a common mechanism by which cross-resistance provides protection against multiple compounds?

Answer: Activation of a single efflux pump.

Explanation: A common mechanism of cross-resistance is the activation or increased expression of a single efflux pump, which can expel various toxic substances, including multiple antimicrobial compounds, from the cell.

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In the context of microorganisms, particularly viruses, how is cross-resistance broadly defined?

Answer: Resistance to multiple distinct antimicrobial agents resulting from a single molecular mechanism.

Explanation: For microorganisms, cross-resistance is broadly defined as resistance to multiple distinct antimicrobial agents that results from a single underlying molecular mechanism.

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To what extent does structural similarity predict cross-resistance between compounds?

Answer: It is generally a weak predictor, and does not predict it at all when aminoglycosides are excluded.

Explanation: Structural similarity is generally a weak predictor of cross-resistance, and its predictive value is further diminished when aminoglycosides are not considered.

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What is identified as the most common cause of cross-resistance?

Answer: Target similarity.

Explanation: The most common cause of cross-resistance is identified as target similarity, where different antimicrobial agents share the same biological target or pathway.

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Cross-Resistance in Antimicrobial Agents

In bacteria, resistance to ciprofloxacin can lead to cross-resistance to nalidixic acid because both are quinolone antibiotics that inhibit topoisomerase.

Answer: True

Explanation: The source explicitly states that resistance to ciprofloxacin can lead to cross-resistance to nalidixic acid due to their shared mechanism of inhibiting topoisomerase.

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Cross-resistance is generally considered beneficial for antimicrobial treatments like phage therapy, as it enhances their long-term effectiveness.

Answer: False

Explanation: Cross-resistance is detrimental to antimicrobial treatments, as it can lead to a rapid loss of effectiveness, making it a critical factor to manage in evolutionary therapies.

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Cross-resistance plays a significant role in the increasing development of multidrug resistance in bacteria, contributing to the broader problem of antibiotic resistance.

Answer: True

Explanation: Cross-resistance is a significant factor in the development of multidrug resistance in bacteria, exacerbating the global challenge of antibiotic resistance.

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Antibiotic resistance always arises as a direct consequence of exposure to an antimicrobial compound.

Answer: False

Explanation: Antibiotic resistance can emerge through various pathways and is not exclusively a direct result of exposure to an antimicrobial compound.

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Which pair of antibiotics exemplifies cross-resistance in bacteria due to shared inhibition of topoisomerase?

Answer: Nalidixic acid and Ciprofloxacin

Explanation: The source identifies nalidixic acid and ciprofloxacin as an example of cross-resistance in bacteria, as both are quinolone antibiotics that inhibit topoisomerase.

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How does cross-resistance primarily affect the effectiveness of antimicrobial treatments like phage therapy?

Answer: It leads to a rapid loss of effectiveness against bacteria.

Explanation: Cross-resistance can cause antimicrobial treatments, including phage therapy, to rapidly lose their effectiveness against target bacteria.

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What is a significant consequence of cross-resistance in clinical medicine?

Answer: It contributes to the increasing development of multidrug resistance in bacteria.

Explanation: A significant consequence of cross-resistance in clinical medicine is its contribution to the increasing development of multidrug resistance in bacteria, complicating treatment options.

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According to the source, is antibiotic resistance always a direct result of exposure to an antimicrobial compound?

Answer: No, it can emerge through multiple pathways.

Explanation: The source explicitly states that antibiotic resistance can emerge through multiple pathways and is not necessarily a direct result of exposure to an antimicrobial compound.

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Cross-Resistance in Pest Management

In pest management, cross-resistance specifically refers to resistance developed by pest populations to pesticides from different chemical families.

Answer: False

Explanation: In pest management, cross-resistance refers to resistance to multiple pesticides that belong to the *same* chemical family, often due to shared binding target sites.

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Cadherin mutations in *Helicoverpa armigera* can result in cross-resistance to Cry1Aa and Cry1Ab proteins, which are insecticidal proteins from *Bacillus thuringiensis*.

Answer: True

Explanation: The source provides this as a specific example of cross-resistance in pest management, where cadherin mutations confer resistance to related insecticidal proteins.

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Multiple resistance is distinct from cross-resistance because it involves resistance to several pesticides through different resistance mechanisms.

Answer: True

Explanation: Multiple resistance is characterized by resistance to several pesticides via *different* mechanisms, whereas cross-resistance involves resistance to multiple substances through a *single shared* mechanism.

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In pest management, cross-resistance is defined by the development of resistance to multiple pesticides that share what characteristic?

Answer: They belong to the same chemical family.

Explanation: In pest management, cross-resistance is specifically defined as resistance to multiple pesticides that belong to the same chemical family, often due to shared target sites.

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What specific genetic alteration in *Helicoverpa armigera* leads to cross-resistance to Cry1Aa and Cry1Ab proteins?

Answer: Cadherin mutations

Explanation: Cadherin mutations in *Helicoverpa armigera* are identified as the genetic alteration leading to cross-resistance against Cry1Aa and Cry1Ab proteins.

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How does 'multiple resistance' fundamentally differ from 'cross-resistance' in the context of pesticides?

Answer: Multiple resistance develops through different resistance mechanisms, unlike cross-resistance which uses a single shared mechanism.

Explanation: Multiple resistance involves distinct resistance mechanisms for different pesticides, whereas cross-resistance arises from a single mechanism conferring resistance to multiple compounds.

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Environmental Influences on Resistance

Exposure to certain disinfectants can lead to antibiotic cross-resistance by increasing the expression of efflux pump genes.

Answer: True

Explanation: Exposure to disinfectants can induce the overexpression of efflux pump genes, leading to cross-resistance against both disinfectants and various antibiotics.

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Cross-resistance between antibiotics and metals is impossible because their chemical structures are fundamentally different.

Answer: False

Explanation: Cross-resistance between antibiotics and metals is possible, even with dissimilar structures, if a shared cellular mechanism, such as an efflux transporter, is involved in their removal.

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Experimental studies have shown that exposure to zinc can decrease bacterial resistance to antibiotics.

Answer: False

Explanation: Experimental studies have demonstrated that exposure to zinc can lead to *increased* bacterial resistance to antibiotics, not decreased.

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The presence of heavy metals in the environment can contribute to the development of antibiotic resistance in microorganisms.

Answer: True

Explanation: Environmental factors, including exposure to heavy metals, can contribute to the development of antibiotic resistance in microorganisms through mechanisms like cross-resistance.

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How can exposure to disinfectants lead to cross-resistance to antibiotics?

Answer: By increasing the expression of genes coding for efflux pumps.

Explanation: Exposure to certain disinfectants can induce the increased expression of efflux pump genes, which then confer cross-resistance to both disinfectants and various antibiotics.

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Which of the following statements is true regarding cross-resistance between antibiotics and metals?

Answer: It can occur if the same cellular mechanism is used to remove both types of compounds.

Explanation: Cross-resistance between antibiotics and metals can occur if a shared cellular mechanism, such as a multi-drug efflux transporter, is utilized to remove both types of compounds from the cell.

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What experimental evidence supports the link between metal exposure and antibiotic resistance?

Answer: Research reporting cross-resistance to various metals and antibiotics through efflux systems.

Explanation: Experimental studies have reported cross-resistance to various metals and antibiotics, often mediated by mechanisms like drug efflux systems, supporting a link between metal exposure and antibiotic resistance.

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What broader implication does cross-resistance between metals and antibiotics have for antibiotic resistance?

Answer: It indicates that environmental factors like heavy metal exposure can contribute to resistance.

Explanation: The cross-resistance between metals and antibiotics implies that environmental factors, such as heavy metal exposure, can significantly contribute to the development and spread of antibiotic resistance in microorganisms.

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Collateral Sensitivity: Concept and Application

Collateral sensitivity is a phenomenon where resistance to one drug leads to increased resistance to another different drug.

Answer: False

Explanation: Collateral sensitivity is defined as the development of resistance to one drug leading to *increased susceptibility* (sensitivity) to a different drug, not increased resistance.

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Collateral sensitivity has only been observed and studied in bacterial pathogens.

Answer: False

Explanation: Collateral sensitivity has been studied in both bacterial and pathogenic fungal organisms, indicating its broader relevance in microbial resistance.

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Collateral sensitivity-based treatments have shown effectiveness against resistant populations in laboratory settings, offering promise for combating cross-resistance.

Answer: True

Explanation: Collateral sensitivity-based treatments have demonstrated effectiveness against resistant populations in *in vitro* studies, suggesting a promising strategy for managing drug resistance.

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The individual mechanisms for collateral sensitivity are fully understood and involve a direct enhancement of organism fitness.

Answer: False

Explanation: The specific individual mechanisms underlying collateral sensitivity are not yet fully understood, and it is theorized to involve a trade-off where resistance benefits might be balanced by reduced organism fitness.

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Collateral sensitivity-based treatments are being explored for multidrug-resistant pathogens like *Staphylococcus aureus* and *Candida auris*.

Answer: True

Explanation: Collateral sensitivity-based treatments are being investigated for their potential application against multidrug-resistant pathogens such as methicillin-resistant *Staphylococcus aureus* and *Candida auris*.

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What is collateral sensitivity in the context of drug resistance?

Answer: The development of resistance to one drug leading to increased susceptibility to another different drug.

Explanation: Collateral sensitivity is a phenomenon where the acquisition of resistance to one drug results in an increased susceptibility to a different drug.

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In which types of organisms has collateral sensitivity been studied?

Answer: In both bacteria and pathogenic fungi.

Explanation: Collateral sensitivity has been investigated and observed in both bacterial and pathogenic fungal organisms.

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What is theorized about the relationship between collateral sensitivity and antimicrobial resistance regarding organism fitness?

Answer: They exist as a trade-off, where resistance benefits might be balanced by risks like reduced organism fitness.

Explanation: It is theorized that collateral sensitivity and antimicrobial resistance represent a trade-off, where the benefits of resistance may be counterbalanced by potential reductions in overall organism fitness.

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For which of the following multidrug-resistant pathogens could collateral sensitivity-based treatments potentially be utilized in the future?

Answer: Methicillin-resistant Staphylococcus aureus and Candida auris.

Explanation: Collateral sensitivity-based treatments are being explored for future application against significant multidrug-resistant pathogens, including methicillin-resistant *Staphylococcus aureus* and *Candida auris*.

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