scholarly journals CRISPR-Cas systems are widespread accessory elements across bacterial and archaeal plasmids

2021 ◽  
Author(s):  
Rafael Pinilla-Redondo ◽  
Jakob Russel ◽  
David Mayo-Muñoz ◽  
Shiraz A Shah ◽  
Roger A Garrett ◽  
...  

Many prokaryotes encode CRISPR-Cas systems as immune protection against mobile genetic elements (MGEs), yet, a number of MGEs also harbor CRISPR-Cas components. With a few exceptions, CRISPR-Cas loci encoded on MGEs are uncharted and a comprehensive analysis of their distribution, prevalence, diversity, and function is lacking. Here, we systematically investigated CRISPR-Cas loci across the largest curated collection of natural bacterial and archaeal plasmids. CRISPR-Cas loci are widely but heterogeneously distributed across plasmids and, in comparison to host chromosomes, their mean prevalence per Mbp is higher and their distribution is markedly distinct. Furthermore, the spacer content of plasmid CRISPRs exhibits a strong targeting bias towards other plasmids, while chromosomal arrays are enriched with virus-targeting spacers. These contrasting targeting preferences dominate across the diversity of CRISPR-Cas subtypes and host taxa, highlighting the genetic independence of plasmids and suggesting a major role of CRISPR-Cas for mediating plasmid-plasmid conflicts. Altogether, CRISPR-Cas are frequent accessory components of many plasmids, which is an overlooked phenomenon that possibly facilitates their dissemination across microbiomes.

2021 ◽  
Author(s):  
Rafael Pinilla-Redondo ◽  
Jakob Russel ◽  
David Mayo-Muñoz ◽  
Shiraz A Shah ◽  
Roger A Garrett ◽  
...  

Abstract Many prokaryotes encode CRISPR-Cas systems as immune protection against mobile genetic elements (MGEs), yet a number of MGEs also harbor CRISPR-Cas components. With a few exceptions, CRISPR-Cas loci encoded on MGEs are uncharted and a comprehensive analysis of their distribution, prevalence, diversity, and function is lacking. Here, we systematically investigated CRISPR-Cas loci across the largest curated collection of natural bacterial and archaeal plasmids. CRISPR-Cas loci are widely but heterogeneously distributed across plasmids and, in comparison to host chromosomes, their mean prevalence per Mbp is higher and their distribution is distinct. Furthermore, the spacer content of plasmid CRISPRs exhibits a strong targeting bias towards other plasmids, while chromosomal arrays are enriched with virus-targeting spacers. These contrasting targeting preferences highlight the genetic independence of plasmids and suggest a major role for mediating plasmid-plasmid conflicts. Altogether, CRISPR-Cas are frequent accessory components of many plasmids, which is an overlooked phenomenon that possibly facilitates their dissemination across microbiomes.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Johann Peltier ◽  
Audrey Hamiot ◽  
Julian R. Garneau ◽  
Pierre Boudry ◽  
Anna Maikova ◽  
...  

AbstractToxin-antitoxin (TA) systems are widespread on mobile genetic elements and in bacterial chromosomes. In type I TA, synthesis of the toxin protein is prevented by the transcription of an antitoxin RNA. The first type I TA were recently identified in the human enteropathogen Clostridioides difficile. Here we report the characterization of five additional type I TA within phiCD630-1 (CD0977.1-RCd11, CD0904.1-RCd13 and CD0956.3-RCd14) and phiCD630-2 (CD2889-RCd12 and CD2907.2-RCd15) prophages of C. difficile strain 630. Toxin genes encode 34 to 47 amino acid peptides and their ectopic expression in C. difficile induces growth arrest that is neutralized by antitoxin RNA co-expression. We show that type I TA located within the phiCD630-1 prophage contribute to its stability and heritability. We have made use of a type I TA toxin gene to generate an efficient mutagenesis tool for this bacterium that allowed investigation of the role of these widespread TA in prophage maintenance.


2020 ◽  
Vol 117 (27) ◽  
pp. 15755-15762
Author(s):  
Jerónimo Rodríguez-Beltrán ◽  
Vidar Sørum ◽  
Macarena Toll-Riera ◽  
Carmen de la Vega ◽  
Rafael Peña-Miller ◽  
...  

Mobile genetic elements (MGEs), such as plasmids, promote bacterial evolution through horizontal gene transfer (HGT). However, the rules governing the repertoire of traits encoded on MGEs remain unclear. In this study, we uncovered the central role of genetic dominance shaping genetic cargo in MGEs, using antibiotic resistance as a model system. MGEs are typically present in more than one copy per host bacterium, and as a consequence, genetic dominance favors the fixation of dominant mutations over recessive ones. In addition, genetic dominance also determines the phenotypic effects of horizontally acquired MGE-encoded genes, silencing recessive alleles if the recipient bacterium already carries a wild-type copy of the gene. The combination of these two effects governs the catalog of genes encoded on MGEs. Our results help to understand how MGEs evolve and spread, uncovering the neglected influence of genetic dominance on bacterial evolution. Moreover, our findings offer a framework to forecast the spread and evolvability of MGE-encoded genes, which encode traits of key human interest, such as virulence or antibiotic resistance.


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