Microbial defenses against mobile genetic elements and viruses: Who defends whom from what?

Abstract

Prokaryotes have numerous mobile genetic elements (MGEs) that mediate horizontal gene transfer (HGT) between cells. These elements can be costly, even deadly, and cells use numerous defense systems to filter, control, or inactivate them. Recent studies have shown that prophages, conjugative elements, their parasites (phage satellites and mobilizable elements), and other poorly described MGEs encode defense systems homologous to those of bacteria. These constitute a significant fraction of the repertoire of cellular defense genes. As components of MGEs, these defense systems have presumably evolved to provide them, not the cell, adaptive functions. While the interests of the host and MGEs are aligned when they face a common threat such as an infection by a virulent phage, defensive functions carried by MGEs might also play more selfish roles to fend off other antagonistic MGEs or to ensure their maintenance in the cell. MGEs are eventually lost from the surviving host genomes by mutational processes and their defense systems can be co-opted when they provide an advantage to the cell. The abundance of defense systems in MGEs thus sheds new light on the role, effect, and fate of the so-called “cellular defense systems,” whereby they are not only merely microbial defensive weapons in a 2-partner arms race, but also tools of intragenomic conflict between multiple genetic elements with divergent interests that shape cell fate and gene flow at the population level.

Efficacy of plasmid-encoded CRISPR-Cas antimicrobial is affected by competitive factors found in wildEnterococcus faecalisisolates

“…Because this phenotype was specific to the fecal isolates, we speculate that these isolates —being more recent, and less domesticated than our model strains— may be better adapted to prevent horizontal gene transfer of MGEs. Studies have shown that MGEs harbor many defense mechanisms (44). It has been argued that the high prevalence of defense systems in bacterial genomes is due to the continuous acquisition of MGEs harboring such systems (44).…”

“…Studies have shown that MGEs harbor many defense mechanisms (44). It has been argued that the high prevalence of defense systems in bacterial genomes is due to the continuous acquisition of MGEs harboring such systems (44). It is possible that these fecal isolates acquired multiple defense systems through HGT while existing in the gut microenvironment.…”

“…While we were unable to identify known anti-plasmid defense systems within the genomes of the fecal isolates, we cannot rule out the existence of such mechanisms within their genomes. The increasing number of defense systems found thus far across numerous bacterial genomes suggest that many of the genes with unknown functions may be defense systems (44).…”

Phage-inducible chromosomal islands promote genetic variability by blocking phage reproduction and protecting transductants from phage lysis

“…Based on the known ability of SaPIs to interfere with phage replication, we hypothesized that SaPIs, like other phage defense mechanisms [ 15 , 28 , 29 ], might benefit the bacterial population by allowing for the survival of an increased number of transductants after horizontal acquisition of bacterial DNA. Here we report that SaPIs promote the survival of bacterial cells after phage-mediated gene transfer by interfering with phage reproduction and reducing the population of infective phage particles.…”

Adaptation by Type III CRISPR-Cas Systems: Breakthrough Findings and Open Questions

“…Prokaryotic cells evolved multiple strategies to defend against viruses and non-beneficial plasmids, including abortive infection, restriction–modification systems ( Sturino and Klaenhammer, 2006 ; Rocha and Bikard, 2022 ), and recently discovered CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated gene) systems ( Makarova et al, 2011 , 2020b ; Hille et al, 2018 ; Nussenzweig and Marraffini, 2020 ). The sequence-specific and adaptive defense activity of a CRISPR-Cas system is acquired by adaptation, during which a short fragment (protospacer) of the foreign DNA is captured and integrated into the CRISPR locus at the leader proximal end as a spacer, simultaneously with a duplication of the first repeat ( Barrangou et al, 2007 ; Bhaya et al, 2011 ; Arslan et al, 2014 ; Heler et al, 2014 ).…”