Species-specific prophage induction by ciprofloxacin in human gut metagenomes

Ben Sakdinan1, Anshul Sinha2, Firdausi Qadri3

  • 1Department of Microbiology & Immunology, McGill University, Montréal, QC, Canada.

Insights

Antibiotic exposure does not broadly induce prophages in the human gut microbiome. However, ciprofloxacin specifically increases phage induction in certain bacterial species, showing varied responses over time.

Area of Science:

  • Microbiology and Virology
  • Human Microbiome Research
  • Antibiotic Resistance and Phage Interactions

Background:

  • Bacteriophages (phages) are viruses that infect bacteria, with two life cycles: lytic and lysogenic.
  • In the lysogenic cycle, phages integrate as prophages into the bacterial genome.
  • Prophage induction, a switch to the lytic cycle, leads to host cell lysis and viral particle release.

Purpose of the Study:

  • To investigate whether antibiotic exposure triggers prophage induction within the human gut microbiome.
  • To assess the association between antibiotic exposure and prophage induction using a metagenomic approach.
  • To provide in vivo evidence of prophage induction in the human gut, complementing in vitro studies.

Main Methods:

  • Utilized a metagenomic approach to analyze samples from two independent human cohorts.
  • Compared prophage to bacterial host read depth ratios (P:H) in relation to antibiotic exposure.
  • Examined P:H ratios across different bacterial species and over the course of antibiotic treatment.

Main Results:

  • Prophage induction was not broadly associated with antibiotic exposures at the overall microbiome level.
  • Ciprofloxacin exposure was found to increase P:H ratios in specific bacterial species.
  • Observed heterogeneous trajectories of P:H ratios during antibiotic exposure, with some remaining high and others returning to baseline.

Conclusions:

  • Antibiotic-induced prophage induction is not a widespread phenomenon in the human gut microbiome.
  • Specific antibiotics, like ciprofloxacin, can induce prophages in particular bacterial species in vivo.
  • The study provides crucial in vivo evidence of phage induction in the human gut, highlighting species-specific effects and dynamic responses.

Related Concept Videos

Introduction to the Human Microbiota01:22

Introduction to the Human Microbiota

Microorganisms colonize various regions of the human body, including the mouth, nasal passages, throat, stomach, intestines, urogenital tract, and skin. The total number of microbial cells is estimated to range from 10¹³ to 10¹⁴—comparable to, or exceeding, the number of human somatic cells. This host–microbiome relationship has led to the conceptualization of humans as supraorganisms, wherein microbial communities perform vital roles in development, immunity,...
98
Lysogenic Cycle of Bacteriophages00:43

Lysogenic Cycle of Bacteriophages

In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
69.7K
Genomic DNA in Prokaryotes00:46

Genomic DNA in Prokaryotes

The genome of most prokaryotic organisms consists of double-stranded DNA organized into one circular chromosome in a region of cytoplasm called the nucleoid. The chromosome is tightly wound, or supercoiled, for efficient storage. Prokaryotes also contain other circular pieces of DNA called plasmids. These plasmids are smaller than the chromosome and often carry genes that confer adaptive functions, such as antibiotic resistance.
Genomic Diversity in Bacteria
Although bacterial genomes are much...
50.9K
Transduction01:16

Transduction

Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome...
2.8K
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
69
Viral Replication: Lysogenic Cycle01:16

Viral Replication: Lysogenic Cycle

The lysogenic cycle is a crucial viral replication strategy that allows bacteriophages to persist within host cells without immediately destroying them. This process is primarily observed in temperate phages, such as bacteriophage lambda (λ), which infects Escherichia coli. The cycle allows the viral genome to persist across bacterial generations while keeping host cells viable.Integration of the Viral GenomeUpon infection, bacteriophage lambda attaches to the bacterial surface and injects...
2.5K