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?

<p>By lateral gene transfer via plasmids (A)</p> Signup and view all the answers

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

<p>They activate and become lytic to combat stress from pathogens. (A)</p> Signup and view all the answers

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

<p>By facilitating the recovery of microbiome diversity after disturbances. (A)</p> Signup and view all the answers

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

<p>To carry accessory genes that provide survival advantages (B)</p> Signup and view all the answers

What occurs within the phage–bacteria network during dysbiosis?

<p>New phage-host networks are established in the new steady states. (B)</p> Signup and view all the answers

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

<p>The simultaneous selection of multiple resistance genes on the same plasmid (B)</p> Signup and view all the answers

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

<p>Dormant antibiotic-resistant cells that can cause reinfection (A)</p> Signup and view all the answers

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

<p>They may provide unknown fitness benefits beyond resistance (C)</p> Signup and view all the answers

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

<p>Siderophores (C)</p> Signup and view all the answers

Which of the following statements about plasmids is true?

<p>Plasmids can carry genes for antibiotic resistance and other functions (C)</p> Signup and view all the answers

What is the main characteristic of pseudolysogeny in viral infections?

<p>Viral DNA exists as an episomal plasmid until conditions are favorable. (C)</p> Signup and view all the answers

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

<p>Increased susceptibility to superinfection. (C)</p> Signup and view all the answers

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

<p>Hosts evolve mechanisms to inhibit phage infection. (B)</p> Signup and view all the answers

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

<p>CRISPR acquires spacers from encountered phages to form a defense. (B)</p> Signup and view all the answers

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

<p>They encode anti-CRISPR proteins to counteract bacterial immunity. (D)</p> Signup and view all the answers

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

<p>By facilitating the exchange of beneficial genes between hosts. (A)</p> Signup and view all the answers

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

<p>Secretion of specific antiviral enzymes. (A)</p> Signup and view all the answers

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

<p>Successful prevention of all phages from attaching to the host. (A)</p> Signup and view all the answers

What significant antibiotic was discovered by Alexander Fleming in 1928?

<p>Penicillin (C)</p> Signup and view all the answers

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

<p>It reduces overall diversity, including loss of important taxa. (C)</p> Signup and view all the answers

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

<p>Alteration of PBPs (B)</p> Signup and view all the answers

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

<p>It degrades the antibiotic outside the bacterial cell. (C)</p> Signup and view all the answers

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

<p>Loss of competition for resources due to decreased diversity (D)</p> Signup and view all the answers

Which of the following describes de novo colonizer bacteria?

<p>They flourish after the reduction of other taxa post-antibiotic treatment. (C)</p> Signup and view all the answers

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

<p>During WW2 (D)</p> Signup and view all the answers

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

<p>It reduces colonization resistance due to loss of important taxa. (A)</p> 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?

<p>Better fitness due to higher beta-lactamase gene dosage (D)</p> Signup and view all the answers

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

<p>Phageome (B)</p> Signup and view all the answers

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

<p>Release (C)</p> Signup and view all the answers

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

<p>They can serve as biomarkers for bacterial diseases (A)</p> Signup and view all the answers

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

<p>Phage abundance increases with age alongside gut microbial diversity (C)</p> Signup and view all the answers

Which characteristic describes lytic phages compared to lysogenic phages?

<p>They replicate and immediately cause host cell lysis (A)</p> Signup and view all the answers

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

<p>Reduction in Caudovirales phage diversity (C)</p> Signup and view all the answers

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

<p>dsDNA, ssDNA, dsRNA, or ssRNA (A)</p> Signup and view all the answers

How do lytic phages influence bacterial taxa in the microbiome?

<p>By specifically infecting the fastest-growing sensitive bacterial populations. (C)</p> Signup and view all the answers

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

<p>Rapid recovery of microbiome diversity after disturbances. (A)</p> Signup and view all the answers

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

<p>During stress situations caused by pathogens invading the community. (B)</p> Signup and view all the answers

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

<p>New phage-host networks are established in the new steady state. (B)</p> Signup and view all the answers

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

<p>Colonization resistance mechanisms such as metabolic competition. (C)</p> Signup and view all the answers

What role do efflux pumps play in antibiotic resistance?

<p>They pump antibiotics out of the bacterial cell. (D)</p> Signup and view all the answers

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

<p>They may offer other unknown fitness benefits. (C)</p> Signup and view all the answers

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

<p>It relates to rare individuals in a bacterial population having pre-existing resistance genes. (C)</p> Signup and view all the answers

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

<p>It increases the likelihood of resistance to different antibiotics being selected together. (B)</p> Signup and view all the answers

What is an episome in relation to plasmids?

<p>A non-essential genetic element that can integrate into the bacterial chromosome. (B)</p> Signup and view all the answers

How do bacteria utilize plasmids to spread antibiotic resistance?

<p>By horizontal gene transfer between different species. (D)</p> Signup and view all the answers

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

<p>Antibiotic-resistant bacteria that hide in the body after treatment. (B)</p> Signup and view all the answers

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

<p>They often include additional genes that confer other survival advantages. (B)</p> Signup and view all the answers

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

<p>Mediating genetic exchange between hosts (B)</p> Signup and view all the answers

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

<p>Lysogenic phages can enter a dormant phase within the host. (A)</p> Signup and view all the answers

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

<p>Stress conditions (D)</p> Signup and view all the answers

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

<p>Phage and bacterial alpha diversity is low initially. (D)</p> Signup and view all the answers

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

<p>Induction of chronic bacterial infections (B)</p> Signup and view all the answers

What is a characteristic of pseudolysogeny?

<p>Viral DNA exists as an episome until conditions are favorable (D)</p> Signup and view all the answers

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

<p>Presence of multiple genome types (dsDNA, ssDNA, dsRNA, ssRNA) (D)</p> Signup and view all the answers

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

<p>Protects from infection by other viruses (D)</p> Signup and view all the answers

During the CRISPR adaptation phase, how are spacers acquired?

<p>From phages that the bacteria encounter (C)</p> Signup and view all the answers

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

<p>The microbial community's genetic makeup (C)</p> Signup and view all the answers

What mechanism might a phage employ to counteract host resistance?

<p>Encoding anti-CRISPR proteins (D)</p> 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?

<p>Increased gene dosage from multiple plasmid copies (C)</p> Signup and view all the answers

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

<p>To recognize and cleave invading viral DNA (A)</p> Signup and view all the answers

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

<p>Lytic cycle (A)</p> Signup and view all the answers

Which of the following statements about phage resistance is true?

<p>Host mutations can prevent phage adsorption or injection (A)</p> Signup and view all the answers

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

<p>They guide Cas9 to cleave matching DNA sequences of invading phages (D)</p> Signup and view all the answers

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

<p>Pioneered the large-scale screening for antibiotics from soil actinomycetes. (B)</p> Signup and view all the answers

What impact do antibiotics have on microbial diversity within communities?

<p>They predominantly stimulate the growth of opportunistic bacteria. (C)</p> Signup and view all the answers

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

<p>Efflux pump mechanisms (B)</p> Signup and view all the answers

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

<p>They proliferate in higher abundance after initial colonization. (C)</p> Signup and view all the answers

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

<p>Antibiotic modification (A)</p> Signup and view all the answers

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

<p>Penicillin was first successfully produced for therapeutic use in 1938. (D)</p> Signup and view all the answers

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

<p>Bacteria that become pathogenic due to decreased competition. (A)</p> Signup and view all the answers

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

<p>Alexander Fleming (A)</p> Signup and view all the answers

Flashcards

Antibiotic Resistance

The ability of bacteria to survive and multiply in the presence of antibiotics.

Antibiotic Mutation

Changes in DNA of bacteria that alter their ability to be killed by antibiotics altering the target site.

Antibiotic Degradation

Bacteria can break down antibiotics outside the cell, rendering them inactive.

Antibiotic Inactivation

Bacteria modify antibiotics so that they can't bind to or affect their target.

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Antibiotic Efflux

Bacteria actively pump antibiotics out of the cell, preventing them from working.

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Antibiotic Target Alteration

Bacteria change the structure of proteins or other molecules that antibiotics are designed to bind to so antibiotic can't affect the target.

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Penicillin-Binding Proteins (PBPs) Mutations

Mutations in PBPs prevent antibiotics like methicillin from binding and affecting bacterial cell wall synthesis.

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Beta-Lactamase

An enzyme produced by some bacteria that breaks down penicillin-like antibiotics.

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Antibiotic Resistance Mechanisms

Methods bacteria use to survive antibiotic treatments. These include inactivation of the antibiotic, reduced uptake, or active removal.

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Plasmid

Small, circular DNA molecule separate from a cell's main chromosome. Often carries genes not essential for survival.

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Antibiotic Resistance Gene Spread (bacteria)

Antibiotic resistance genes spread quickly between bacteria via plasmids and other mechanisms.

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Co-selection

The selection of multiple antibiotic resistance genes on the same plasmid.

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Plasmid Paradox

Plasmids carrying antibiotic resistance genes persist even without antibiotic pressure, implying potential benefits beyond just resistance.

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Persister Reservoirs

Antibiotic-resistant cells that survive in a host even after treatment.

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Episome

A non-essential genetic element that can replicate independently or integrate into a chromosome.

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Plasmid Replication

Plasmids are DNA molecules that replicate independently from the host chromosome and prioritize their own replication.

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Bacteriophages

Viruses that infect bacteria; they are essential components of microbiomes.

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Lytic Cycle

A viral replication cycle where the virus replicates and immediately lyses (breaks open) the host cell.

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Lysogenic Cycle

A viral replication cycle where the virus integrates its DNA into the host's DNA, becoming dormant.

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Phageome

The collection of all viruses (bacteriophages) present in a microbiome.

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Phage vs. microbiome diversity

Viral and bacterial diversity are related, such that shifts in one affect the other.

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Plasmid fitness advantage

Cells with plasmids often have a survival advantage due to multiple copies of the genes they carry.

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Viral genome types

Viral genomes can be either double-stranded DNA, single-stranded DNA, double-stranded RNA, or single-stranded RNA.

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Lysogeny

A state where a bacteriophage's DNA integrates (as a prophage) into the host bacterium's genome without immediate destruction.

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Prophage

Bacteriophage DNA integrated into the host's bacterial genome.

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CRISPR/Cas9

A bacterial immune system utilizing an array of DNA sequences (spacers) to target and destroy invading viral DNA, like a bacterial immune defence.

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Phage-Host Arms Race

Constant evolutionary struggle between bacteriophages and their bacterial hosts. Bacteria evolve defence mechanisms like CRISPR against viruses, while phages evolve ways to overcome these defenses.

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Pseudolysogeny

Maintenance of phage DNA as an episomal plasmid within the host genome rather than integration.

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Horizontal Gene Transfer (HGT)

Transfer of genetic material between unrelated species, sometimes through bacteriophages.

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Restriction Modification Systems

Bacterial defence mechanisms that recognize and cleave foreign DNA (like phage DNA), protecting the bacterial genome.

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Phage role in colonization resistance

Bacteriophages can affect colonization resistance, either helping or hindering it. Pro-phages (lysogenic) can become active (lytic) during stress from pathogens, infecting other bacteria (lytic or lysogenic). This limits fast-growing bacteria, which could be either beneficial or harmful.

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Resilience in phageome

Microbiomes, with a functioning phage network, recover quickly after disturbances like antibiotic treatment or a shift in bacteria types (dysbiosis). New phage-bacteria interactions form, and this recovery might include the transfer of beneficial genes between bacteria.

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Dysbiosis and phage networks

Changes in the microbial community (dysbiosis) also affect the phage-bacteria interactions. New relationships between phages and bacteria are formed, leading a new steady state

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Prophage activation

Prophages (dormant viral forms) can become active (lytic) viruses in response to stress from pathogens, leading them to infect other bacteria.

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Phage-mediated gene transfer

Phages may move beneficial genes from one bacteria to another, contributing to microbiome resilience after dysbiosis (microbial imbalance).

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Antibiotic Discovery

The process of finding and developing new antibiotics, starting with penicillin and then expanding to many other types.

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What do penicillin-binding proteins (PBPs) do?

PBPs are bacterial proteins that help build the cell wall. Mutations in these proteins can make bacteria resistant to antibiotics like methicillin.

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What is beta-lactamase?

An enzyme produced by bacteria that breaks down penicillin-like antibiotics, making them ineffective.

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Multidrug Transporter

A protein in bacterial cell membranes that pumps antibiotics out of the cell, preventing them from reaching their targets.

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Survivor bacteria

Bacteria that are not susceptible to the antibiotic and survive the treatment.

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Opportunistic bacteria

Bacteria that were initially present at low levels, but can thrive after antibiotic treatment since their competitors are gone.

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De novo colonizer bacteria

New bacterial species that arrive and colonize the space left vacant by antibiotic treatment.

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Antibiotic Resistance Genes

Genes that allow bacteria to survive and multiply in the presence of antibiotics.

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How do plasmids spread antibiotic resistance?

Plasmids can be transferred between bacteria, spreading antibiotic resistance genes even between different species.

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The Plasmid Paradox

Plasmids carrying antibiotic resistance genes persist even without antibiotic pressure. This suggests they may provide benefits beyond just resistance.

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Phageome Resilience

The ability of the phage community (phageome) to adapt and recover after disruptions, such as antibiotic treatment, leading to a new stable state for the microbiome.

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CRISPR-Spacer Record

The CRISPR-spacer region in bacteria stores a record of past phage infections, acting like a bacterial immune memory.

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Phage Resistance

Host mutations that prevent phage adsorption or injection (receptor changes, etc.), CRISPR/Cas9, and superinfection.

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Counter-Resistance

Phages adapt/mutate to overcome host resistance or adapt to new hosts or encode anti-CRISPR proteins (ACRs).

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Plasmid's 'selfish' nature

Plasmids are small, circular DNA molecules that replicate independently within bacteria. Their main goal is to replicate themselves, even if this means potentially harming the host cell.

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Fitness benefit of plasmids

Bacteria carrying plasmids often have a survival advantage because they have multiple copies of the genes on the plasmid, which can provide beneficial traits, such as antibiotic resistance.

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What is a phageome?

The phageome is the collection of all the bacteriophages (viruses that infect bacteria) within a microbiome. It's like the viral community in a particular environment.

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Lytic vs. Lysogenic Cycle

The lytic cycle is a rapid viral replication cycle where the virus destroys the host cell. The lysogenic cycle, however, involves the viral DNA integrating into the host's DNA, becoming dormant and replicating along with the host.

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Phage impact on microbiome diversity

Bacteriophages play a crucial role in shaping the diversity of microbial communities by infecting and killing certain bacteria, thus influencing the overall composition of the microbiome.

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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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