History of Antibiotic Discovery

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Questions and Answers

How do lytic phages affect the growth of bacterial populations in the microbiome?

They enhance the growth of all bacterial populations.

They promote the colonization of pathogenic bacteria.

They have no significant impact on bacterial growth.

They selectively inhibit the fastest-growing sensitive populations. (correct)

What is a potential consequence of the loss or gain of taxa in the microbiome?

Enhanced antibiotic effectiveness.

Altered mechanisms of colonization resistance. (correct)

Increased genetic diversity within the phageome.

Reduced interactions between phages and bacteria.

What mechanism allows some bacteria to resist the effects of penicillin?

Altered ribosomes

Enhanced protein synthesis

Beta-lactamase production (correct)

Increased membranous mitochondria

How do antibiotic resistance genes spread between bacterial species?

By lateral gene transfer via plasmids Signup and view all the answers

What role do pro-phages play in the context of pathogens invading the microbiome?

They activate and become lytic to combat stress from pathogens. Signup and view all the answers

How does resilience in the phageome contribute to the stability of microbial communities?

By facilitating the recovery of microbiome diversity after disturbances. Signup and view all the answers

What is the primary function of a plasmid in bacterial cells?

To carry accessory genes that provide survival advantages Signup and view all the answers

What occurs within the phage–bacteria network during dysbiosis?

New phage-host networks are established in the new steady states. Signup and view all the answers

What is co-selection in the context of antibiotic resistance?

The simultaneous selection of multiple resistance genes on the same plasmid Signup and view all the answers

What is a persister reservoir as described in antibiotic resistance dynamics?

Dormant antibiotic-resistant cells that can cause reinfection Signup and view all the answers

Why might plasmids continue to be maintained in bacterial populations despite potential fitness costs?

They may provide unknown fitness benefits beyond resistance Signup and view all the answers

What is an example of an accessory gene carried by plasmids?

Siderophores Signup and view all the answers

Which of the following statements about plasmids is true?

Plasmids can carry genes for antibiotic resistance and other functions Signup and view all the answers

What is the main characteristic of pseudolysogeny in viral infections?

Viral DNA exists as an episomal plasmid until conditions are favorable. Signup and view all the answers

Which of the following is NOT a benefit of prophage integration in bacterial hosts?

Increased susceptibility to superinfection. Signup and view all the answers

What is a key aspect of the phage-host arms race?

Hosts evolve mechanisms to inhibit phage infection. Signup and view all the answers

What happens during the adaptation phase of CRISPR/Cas9 in bacteria?

CRISPR acquires spacers from encountered phages to form a defense. Signup and view all the answers

What is a method by which phages can exhibit counter-resistance to host defenses?

They encode anti-CRISPR proteins to counteract bacterial immunity. Signup and view all the answers

How do prophages contribute to horizontal gene transfer (HGT)?

By facilitating the exchange of beneficial genes between hosts. Signup and view all the answers

Which mechanism does NOT contribute to phage adsorption and surface resistance in bacteria?

Secretion of specific antiviral enzymes. Signup and view all the answers

Which of the following describes a consequence of phage resistance in bacterial hosts?

Successful prevention of all phages from attaching to the host. Signup and view all the answers

What significant antibiotic was discovered by Alexander Fleming in 1928?

Penicillin Signup and view all the answers

What is one of the consequences of antibiotic treatment on microbial diversity?

It reduces overall diversity, including loss of important taxa. Signup and view all the answers

Which mechanism describes how some bacteria develop resistance by altering the antibiotic target?

Alteration of PBPs Signup and view all the answers

In the context of antibiotic resistance, what role does beta-lactamase play?

It degrades the antibiotic outside the bacterial cell. Signup and view all the answers

What process can lead to the emergence of opportunistic bacteria following antibiotic use?

Loss of competition for resources due to decreased diversity Signup and view all the answers

Which of the following describes de novo colonizer bacteria?

They flourish after the reduction of other taxa post-antibiotic treatment. Signup and view all the answers

During which era did the large-scale screening for antibiotics begin?

During WW2 Signup and view all the answers

What best describes the effect of antibiotics on the colonization resistance of microbiomes?

It reduces colonization resistance due to loss of important taxa. Signup and view all the answers

What advantage do E coli strains with plasmids have over those with the beta-lactamase gene integrated into the chromosome?

Better fitness due to higher beta-lactamase gene dosage Signup and view all the answers

Which term is used to describe all the viral components in a microbiome?

Phageome Signup and view all the answers

During which phase of the viral life cycle do lytic phages ultimately lead to cell death?

Release Signup and view all the answers

What potential role do phages play in the context of microbiomes?

They can serve as biomarkers for bacterial diseases Signup and view all the answers

What is the relationship between phage and bacterial alpha diversity in infants?

Phage abundance increases with age alongside gut microbial diversity Signup and view all the answers

Which characteristic describes lytic phages compared to lysogenic phages?

They replicate and immediately cause host cell lysis Signup and view all the answers

Which factor is linked to shifts in microbial community composition in infants?

Reduction in Caudovirales phage diversity Signup and view all the answers

What type of genetic material can be found in a phage genome?

dsDNA, ssDNA, dsRNA, or ssRNA Signup and view all the answers

How do lytic phages influence bacterial taxa in the microbiome?

By specifically infecting the fastest-growing sensitive bacterial populations. Signup and view all the answers

What does the resilience of the phageome contribute to maintaining in a microbial community?

Rapid recovery of microbiome diversity after disturbances. Signup and view all the answers

In what situation might pro-phages activate and become lytic?

During stress situations caused by pathogens invading the community. Signup and view all the answers

What effect does dysbiosis have on phage-bacteria network interactions?

New phage-host networks are established in the new steady state. Signup and view all the answers

What can the loss or gain of taxa in the microbiome influence?

Colonization resistance mechanisms such as metabolic competition. Signup and view all the answers

What role do efflux pumps play in antibiotic resistance?

They pump antibiotics out of the bacterial cell. Signup and view all the answers

Why might plasmids that carry antibiotic resistance genes be maintained in bacterial populations despite fitness costs?

They may offer other unknown fitness benefits. Signup and view all the answers

What is meant by 'standing variation' in the context of antibiotic resistance?

It relates to rare individuals in a bacterial population having pre-existing resistance genes. Signup and view all the answers

What is the significance of co-selection of multiple antibiotic resistance genes on the same plasmid?

It increases the likelihood of resistance to different antibiotics being selected together. Signup and view all the answers

What is an episome in relation to plasmids?

A non-essential genetic element that can integrate into the bacterial chromosome. Signup and view all the answers

How do bacteria utilize plasmids to spread antibiotic resistance?

By horizontal gene transfer between different species. Signup and view all the answers

In the context of antibiotic pressure, what does the term 'persister reservoirs' refer to?

Antibiotic-resistant bacteria that hide in the body after treatment. Signup and view all the answers

What is a primary characteristic of antibiotic resistance genes located on plasmids?

They often include additional genes that confer other survival advantages. Signup and view all the answers

What mechanism allows bacteriophages to influence genetic diversity in microbial communities?

Mediating genetic exchange between hosts Signup and view all the answers

Which statement accurately describes the differences between lytic and lysogenic phages?

Lysogenic phages can enter a dormant phase within the host. Signup and view all the answers

What can trigger a prophage to switch from the lysogenic cycle to the lytic cycle?

Stress conditions Signup and view all the answers

In infants, what change is observed in the diversity of phages during initial colonization?

Phage and bacterial alpha diversity is low initially. Signup and view all the answers

What is a significant consequence of viral infections on bacterial cells?

Induction of chronic bacterial infections Signup and view all the answers

What is a characteristic of pseudolysogeny?

Viral DNA exists as an episome until conditions are favorable Signup and view all the answers

Which feature of bacteriophages is linked to their role in shaping gut microbiome diversity?

Presence of multiple genome types (dsDNA, ssDNA, dsRNA, ssRNA) Signup and view all the answers

What advantage does a prophage provide to its bacterial host concerning superinfection?

Protects from infection by other viruses Signup and view all the answers

During the CRISPR adaptation phase, how are spacers acquired?

From phages that the bacteria encounter Signup and view all the answers

What can phages reveal about a host's gut microbiome?

The microbial community's genetic makeup Signup and view all the answers

What mechanism might a phage employ to counteract host resistance?

Encoding anti-CRISPR proteins Signup and view all the answers

What is the primary reason E. coli strains with plasmids exhibit higher fitness compared to those with chromosomal beta-lactamase genes?

Increased gene dosage from multiple plasmid copies Signup and view all the answers

What is a significant role of restriction-modification systems in bacterial hosts?

To recognize and cleave invading viral DNA Signup and view all the answers

During which specific cycle do virulent phages cause host cell death?

Lytic cycle Signup and view all the answers

Which of the following statements about phage resistance is true?

Host mutations can prevent phage adsorption or injection Signup and view all the answers

What is the role of small CRISPR RNAs (crRNAs) during the interference phase?

They guide Cas9 to cleave matching DNA sequences of invading phages Signup and view all the answers

Which of the following best describes the contribution of Selman Waksman in antibiotic discovery?

Pioneered the large-scale screening for antibiotics from soil actinomycetes. Signup and view all the answers

What impact do antibiotics have on microbial diversity within communities?

They predominantly stimulate the growth of opportunistic bacteria. Signup and view all the answers

Which mechanism involves bacteria acquiring the ability to pump out antibiotics?

Efflux pump mechanisms Signup and view all the answers

What is a primary characteristic of de novo colonizer bacteria following antibiotic exposure?

They proliferate in higher abundance after initial colonization. Signup and view all the answers

Which category of antibiotic resistance mechanism involves direct modifications to the antibiotic molecule?

Antibiotic modification Signup and view all the answers

Which statement is true regarding the historical context of antibiotic discovery?

Penicillin was first successfully produced for therapeutic use in 1938. Signup and view all the answers

What role does the term 'opportunistic bacteria' describe in the context of altered microbiomes due to antibiotics?

Bacteria that become pathogenic due to decreased competition. Signup and view all the answers

Which historical figure is credited with the discovery of penicillin from the mold Penicillium?

Alexander Fleming Signup and view all the answers

Study Notes

Short History of Antibiotic Discovery

Paul Ehrlich coined the terms "chemotherapy" and "antibiotic," finding a drug (arsphenamine) active against Treponema pallidum (syphilis) in 1910.
Alexander Fleming (1928) discovered penicillin through chance observation of a clearing zone on an agar plate from fungi (Penicillium).
Penicillin was not a therapeutic until Florey and Chain (1938) scaled up its production.
Initially, large amounts of Penicillium culture (2000 liters) were needed to treat one person. World War II spurred further government and industrial scaling of antibiotic production.

Screening for Antibiotic Sensitivity

Selman Waksman screened soil actinomycetes for antibiotic production, discovering actinomycin in 1940 and streptomycin in 1942.
This marked the start of large-scale screening for antibiotics.

Antibiotics and Disruptions of Microbiomes

Antibiotics target conserved cell components like cell walls and membranes, and inhibit processes like replication, transcription, and translation.
Antibiotic treatment reduces microbial diversity, including loss of essential taxa.
Antibiotic use can disrupt metabolic processes in communities, sometimes leading to colonization resistance reduction and antibiotic resistance development.
Survivor bacteria are antibiotic-resistant; lost bacteria are susceptible.
Opportunistic bacteria thrive due to lack of competition after antibiotics.
De novo colonizing bacteria are typically in smaller abundance after antibiotics but then increase.

Antibiotic Resistance Mechanisms

Resistance involves altering antibiotic targets (e.g., mutations in penicillin-binding proteins), degrading antibiotics (e.g., beta-lactamases cleaving penicillins), modifying antibiotics (e.g., adding groups to kanamycin), or pumping antibiotics out of cells (e.g., multidrug transporter NorA in S. aureus).

What Are Plasmids?

Plasmids are extrachromosomal, hereditary determinants ranging from thousands to millions of base pairs (bp).
They are non-essential genetic elements capable of autonomous replication.
Plasmids can contain genes for virulence factors, toxins, bacteriocins, siderophores, metabolism, antibiotic resistance, and disinfectant resistance.
Plasmids can range from thousands to millions of bp, often circular and can be double or single-stranded DNA.
Episomes are non-essential elements that can replicate autonomously or integrate into the chromosome.

Co-selection of Multiple Antibiotic Resistance Genes

Co-selection occurs when antibiotic resistance genes are on the same plasmid, meaning that the selection of one resistance gene will also select for other resistance genes on that plasmid.
This can lead to the transfer of multiple resistance genes to other bacteria during plasmid transfer.

The Plasmid "Paradox"

Antibiotic use is a selective pressure for plasmids with antibiotic resistance genes.
Bacteria with antibiotic resistance genes within plasmids can remain dormant in tissues during antibiotic use, capable of re-emerging when antibiotic pressure is removed.
Plasmids may provide additional fitness benefits unrelated to antibiotic resistance, such as improved metabolic functions, or other benefits not related to antibiotic resistance
The maintenance of plasmids might have associated fitness costs, but these costs are outweighed by antibiotic resistance benefits
Plasmids can be integrated or excised from the bacterial genome

Viruses or Bacteriophages

Bacteriophages have a role in microbiome structure and function, including mediating genetic exchange.
Bacteriophages mediate an exchange of genetic material in the microbiome like plasmids do.
Phages are drivers in microbiome diversity.
Phages can be markers for disease and used in therapy delivery/treatment.
Phages alter microbial diversity in infants, influencing bacterial colonization early in life.

Phage Cycle

Lytic cycle: phages replicate within a host cell and then the host cell lyses.
Lysogenic cycle: Phages integrate their genome into host DNA and replicate along with the host genome. Phage can sometimes be dormant for long periods. A prophage is phage DNA that is integrated into the host cell's genome.

Phage Benefits

Lysogenic phages can influence community composition through horizontal gene transfer of beneficial genes.
They can protect against superinfection (infection by multiple viruses).
Prophages can encode genes for carbohydrate transport, degradation, and antibiotic resistance.

Phage Resistance and Counter-Resistance

Host cells can evolve mechanisms to prevent phage infection (phage resistance).
Phages can respond by adapting to overcome host resistance or to adapt to new hosts.
There are genetic systems like CRISPR-Cas9 that bacteria use as a defense system to counter phage infection by capturing portions of phage DNA and use this information to recognize and destroy.

Phage's role in Colonization Resistance

Bacteriophages can positively or negatively affect colonization resistance.
Lytic phages in the microbiome can limit the growth of specific bacterial species.
The loss or gain of specific microbial taxa, potentially beneficial or harmful, can change resilience that leads to changes in colonization resistance.
Resilience in phageomes plays a role in microbiome stability after perturbations.

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Description

This quiz explores the significant milestones in the discovery and development of antibiotics. From Paul Ehrlich's early work on chemotherapy to Alexander Fleming's serendipitous discovery of penicillin and the subsequent production challenges during World War II, you'll learn about key figures and their contributions. Understand the importance of antibiotic sensitivity screening and its impact on microbiomes.