How do bacteriophages transfer antibiotic resistance genes (ARGs)?

Antibiotics resistance genes transfer by bacteriophage
An illustration of ARG transfer by
T bacteriophages

Introduction

Effective prevention of infectious diseases is becoming a dream day after day due to the rise of antibiotics resistance. The drugs on the pipeline are no longer promising enough to end this worst-case scenario any time soon. The speed of bacteria becoming resistant to a new antibiotic is much higher than the drug development technology. While some bacterial strains display intrinsic resistance (for example, Aeromonas spp to ampicillin), others achieve antibiotic resistance by mutation, recombining foreign DNA into the chromosome, or horizontal gene acquisition. In many cases, these three mechanisms operate together. Several mobile genetic elements (MGEs) have been reported to mobilize different resistance genes, and despite sharing standard features, they are often considered and studied separately. Bacteriophages and phage-related particles have recently been highlighted as MGEs that antibiotic transfer resistance. Some studies suggested that bacteriophages in treating bacterial infections through phage therapy bacteriophages have offered a promising alternative to AMR even though they also contribute to its rise.

Bacteriophages: viral shuttles carrying bacterial DNA

Bacteriophages, Like all viruses, phages are obligate intracellular parasites without intrinsic metabolism, which require the metabolic machinery of the host bacteria to support their reproduction. The complete structure of a phage commonly consists of a nucleic acid core (single or double‐stranded RNA or DNA but not both), an outer shell of protein capsid, and in some cases, a lipid envelope; many of them have additional structures as the tail, aimed to inject the nucleic acid through the cell wall) bacteriophages are ultra‐microscopic (20–200 nm). Herefore, they shall be observed through transmission electron microscopy after capsid staining n fact, the International Committee on Taxonomy of Viruses (ICTV) taxonomic system requires visualization of the phage particles by electron microscopy, among other characteristics, to determine capsid morphology to determine the phage taxonomy.

Phages are recognized to be essential actors in different aspects of bacterial ecology, for example bacterial population regulation, and more specifically, gene, including ARGs, transfer  etagenomic studies confirm that the majority of viruses in the viral fraction of most environments are bacteriophages and that a large proportion of the viral particles contain bacterial DNA sequences, including linear chromosome fragments and mobile elements such as insertion elements, transposons, plasmids and prophages  hey, influence the evolution of most bacterial species by promoting gene transfer  oreover phage-like particles has also evolved, which can package random pieces of host cell's genome  The ubiquity and the great abundance of bacteriophages means that gene transfer from phages to bacteria occurs in a vast array of environments and ecosystems  The occurrence of phages harboring ARGs has been reported in different matrices from the human gut to ready to eat food  ince, bacteriophage‐mediated transfer of antibiotic resistance can occur in laboratories transduction could be a significant contributor to the emergence and persistence of antibiotic resistance in these environments affecting the food chain  n fact, transduction is acknowledged as a potential contributor to the spread of ARGs, especially between members of the same species. Capsid containing bacterial DNA can fully bind to a recipient cell and inject foreign DNA  f the transferred bacterial DNA recombines into the recipient cell's genome or guaranties its autonomous replication (i.e., plasmids) transduction has occurred.

How do bacteriophages promote ARG dissemination?

Phages bind to specific target receptors present on the bacterial cell surface, such that each phage generally targets a very narrow range of strains of the same bacterial species pon adsorption, phages inject their genomes into the bacterial cytoplasm and replicate employing one or two primary life cycles: the lytic cycle or the lysogenic (or temperate) cycle.

Antibiotics resistance genes transfer by bacteriophage
bacteriophage cycle

In the lytic cycle, the phage exploits the host cellular machinery, using it to replicate and manufacture new phage particles that are released following programmed cell lysis of an over‐burdened cell. In some cases, pseudo‐lysogeny can also occur, where the phage genome persists in non‐replicating cells until they return to replication and the bacteriophage follow its lytic cycle.

The phage genome (termed a prophage) integrates into the bacterial genome in the lysogenic cycle. It replicates as part of the host chromosome, or as an independent replicon, in the absence of particle formation or cell lysis nder specific circumstances, those of which induces the bacterial SOS response (antibiotic treatment, oxidative stress, irradiation, or DNA damage), the prophage is generated, and the lytic cycle is activated. Sometimes the phage genome incorporates host DNA from the genes located in the prophage integration locus, whereas those persisting as independent replicons contain random fragments.

During the lytic cycle, released phages can randomly package and transfer bacterial DNA by generalized transduction indeed, some mobile genetic elements have developed elegant and sophisticated strategies to hijack the phage DNA‐packaging machinery for their own transfer   hage infection kills bacterial cells during the lytic cycle, and small parts of bacterial DNA are occasionally captured in viral transducing particles  herewith, bacterial populations containing prophages can be considered drivers of gene transfer in particular genes encoding antibiotic resistance  his context applies too to ARGs; thus, Haaber et al. (2016) demonstrated that the release of phages from a population of S. aureus cells enables the entire prophage‐containing population to acquire ARGs from competing, phage‐susceptible strains present in the same environment  his fact would explain the rapid exchange of ARGs observed in S. aureus particularly and in other pathogenic bacteria although bacteriophages are generally thought to infect only a few strains of a given species, evidence is mounting that phages can have broader host ranges.

References

Dennis H Bamford, Jonathan M Grimes, David I Stuart, What does structure tell us about virus evolution?, Current Opinion in Structural Biology, Volume 15, Issue 6, 2005.
Lerminiaux NA, Cameron ADS. Horizontal transfer of antibiotic resistance genes in clinical environments a J Microbiol  019 Jan;65(1):34-44  oi: 10.1139/cjm-2018-0275. Epub 2018 Sep 24 MID: 30248271.
Maiques E, Ubeda C, Campoy S, Salvador N, Lasa I, Novick RP, Barbé J, Penadés JR. beta-lactam antibiotics induce the SOS response and horizontal transfer of virulence factors in Staphylococcus aureus. J Bacteriol  006 Apr;188(7):2726-9  oi: 10.1128/JB.188.7.2726-2729.2006  MID: 16547063; PMCID: PMC1428414.
Łoś M, Węgrzyn G. Pseudolysogeny. Adv Virus Res. 2012;82:339-49. doi: 10.1016/B978-0-12-394621-8.00019-4. PMID: 22420857. 
Bacteriophages as antibiotic resistance genes carriers in agro‐food systems 
S,. Jebri 
 
F. Rahmani 
 
F. Hamid 
First published: Sep 11, 2020

1 Comments

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