Abortive Infection: Bacterial Suicide as an Antiviral Immune Strategy

Lopatina, Anna; Tal, Nitzan; Sorek, Rotem

doi:10.1146/annurev-virology-011620-040628

Cited by 329 publications

(274 citation statements)

References 88 publications

Supporting

Mentioning

268

Contrasting

Unclassified

Order By: Relevance

“…The lack of insertions in neighbouring genes, however, suggested that this region is essential for cell growth, that the transposon is not able to access it [58] or a part of this genomic island was lost following genome sequencing. The remaining symE genes [3][4][5][6] were predicted pseudogenes with none expressed under standard growth conditions and all tolerating transposon insertions (Table 1). In conclusion, there is evidence of expansion and inactivation of symE genes in Serratia, with one being similar to a previously defined SymE system and two potentially being part of novel type II loci.…”

Section: Dynamic Evolution Of Syme Type I Ta Loci Includes Gene Duplimentioning

confidence: 99%

“…During abortive infection, phages adsorb but infection is followed by bacterial dormancy or death; hence, phage propagation is inhibited and few, if any, phages are released [1,3]. The phenotypic and descriptive definition of abortive infection has resulted in a diverse set of known Abi systems that have a wide range of molecular mechanisms [3,4]. Some Abi systems function via a two-gene toxin-antitoxin (TA) mechanism, such as ToxIN/AbiQ [5,6] and AbiE [7,8].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Functional genomics reveals the toxin–antitoxin repertoire and AbiE activity in Serratia

et al. 2020

View full text Add to dashboard Cite

Bacteriophage defences are divided into innate and adaptive systems. Serratia sp. ATCC 39006 has three CRISPR-Cas adaptive immune systems, but its innate immune repertoire is unknown. Here, we re-sequenced and annotated the Serratia genome and predicted its toxin–antitoxin (TA) systems. TA systems can provide innate phage defence through abortive infection by causing infected cells to ‘shut down’, limiting phage propagation. To assess TA system function on a genome-wide scale, we utilized transposon insertion and RNA sequencing. Of the 32 TA systems predicted bioinformatically, 4 resembled pseudogenes and 11 were demonstrated to be functional based on transposon mutagenesis. Three functional systems belonged to the poorly characterized but widespread, AbiE, abortive infection/TA family. AbiE is a type IV TA system with a predicted nucleotidyltransferase toxin. To investigate the mode of action of this toxin, we measured the transcriptional response to AbiEii expression. We observed dysregulated levels of tRNAs and propose that the toxin targets tRNAs resulting in bacteriostasis. A recent report on a related toxin shows this occurs through addition of nucleotides to tRNA(s). This study has demonstrated the utility of functional genomics for probing TA function in a high-throughput manner, defined the TA repertoire in Serratia and shown the consequences of AbiE induction.

show abstract

Section: Dynamic Evolution Of Syme Type I Ta Loci Includes Gene Duplimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional genomics reveals the toxin–antitoxin repertoire and AbiE activity in Serratia

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Although phages are posited as a solution for antibiotic resistance, bacteria can also evolve resistance to phage infection. Bacteria exist in a constant evolutionary battle with phages, and thus have evolved many systems to resist phage infection, including preventing phage binding, restriction modification systems, CRISPR-Cas9 immunity, and abortive infection 14,15 . Given strong selective pressure from a single phage, bacteria often quickly evolve resistance to that phage in laboratory settings 16 .…”

Section: Introductionmentioning

confidence: 99%

Phage Cocktails can Prevent the Evolution of Phage-ResistantEnterococcus

Wandro

Ghatbale

Attai

et al. 2021

Preprint

View full text Add to dashboard Cite

Antibiotic resistant Enterococcus infections are a major health crisis that requires the development of alternative therapies. Phage therapy could be an alternative to antibiotics and has shown promise in in vitro and in early clinical studies. Phage therapy is often deployed as a cocktail of phages, but there is little understanding of how to most effectively combine phages. Here we utilized a collection of 20 Enterococcus phages to test principles of phage cocktail design and determine the phenotypic effects of evolving phage resistance in Enterococcus isolates that were susceptible or resistant to antibiotics (e.g., Vancomycin Resistant Enterococcus (VRE)). We tested the ability of each phage to clear Enterococcus host cultures and prevent the emergence of phage resistant Enterococcus. We found that some phages which were ineffective individually were effective at clearing the bacterial culture when used in cocktails. To understand the dynamics within phage cocktails, we used qPCR to track which phages increased in abundance in each cocktail, and saw dynamics ranging from one dominant phage to even phage growth. Further, we isolated several phage-resistant mutants to test for altered Vancomycin sensitivity. We found that mutants tended to have no change or slightly increased resistance to Vancomycin. By demonstrating the efficacy of phage cocktails in suppressing growth of antibiotic susceptible and VRE clinical isolates when exposed to phages, this work will help to inform cocktail design for future phage therapy applications.IMPORTANCEAntibiotic resistant Enterococcus infections are a major health crisis that requires the development of alternative therapies. Phage therapy could be an alternative to antibiotics and has shown promise in in vitro and in early clinical studies. Phage therapy in the form of cocktails is often suggested, with similar goals as the combination therapy that has been successful in the treatment of HIV infection, but there is little understanding about how to combine phages most effectively. Here we utilized a collection of 20 Enterococcus phages to test whether several phage cocktails could prevent the host from evolving resistance to therapy and to determine whether evolving resistance to phages affected host susceptibility to antibiotics. We showed that cocktails of two or three unrelated phages often prevented the growth of phage-resistant mutants, when the same phages applied individually were not able to.

show abstract

“…In a mechanism conceptually analogous to the pathogen-stimulated programmed cell death driven by the innate immune systems of higher organisms (Abedon, 2012), phage infection can be prevented from sweeping across populations, at the cost of the lives of infected cells. These population-level phage defense systems are often grouped under the umbrella term “abortive infection” (Abi) (Labrie et al, 2010; Lopatina et al, 2020) but actually represent diverse mechanisms to prevent phage replication and induce cell death. These include protease-mediated inhibition of cellular translation (Bingham et al, 2000), toxin-antitoxin pairs (Fineran et al, 2009; Pecota and Wood, 1996) and cyclic oligonucleotide signalling (Cohen et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Prophage-encoded phage defense proteins with cognate self-immunity

Hinton

Owen

Wenner

et al. 2020

Preprint

View full text Add to dashboard Cite

SummaryTemperate phages are pervasive in bacterial genomes, existing as vertically-inherited islands called prophages. Prophages are vulnerable to the predation of their host bacterium by exogenous phages. Here we identify BstA, a novel family of prophage-encoded phage defence proteins found in diverse Gram-negative bacteria. BstA drives potent suppression of phage epidemics through abortive infection. The bstA-encoding prophage itself is not inhibited by BstA during lytic replication due to a self-immunity mechanism driven by the anti-BstA (aba) element, a short stretch of DNA within the bstA locus. Phage-targeting by distinct BstA proteins from Salmonella, Klebsiella and Escherichia prophages is functionally interchangeable, but each possesses a cognate aba element. The specificity of the aba element ensures that immunity is exclusive to the replicating prophage, and cannot be exploited by heterologous BstA-encoding phages. BstA allows prophages to defend their host cells against exogenous phage attack, without sacrificing their own lytic autonomy.

show abstract

Abortive Infection: Bacterial Suicide as an Antiviral Immune Strategy

Cited by 329 publications

References 88 publications

Functional genomics reveals the toxin–antitoxin repertoire and AbiE activity in Serratia

Functional genomics reveals the toxin–antitoxin repertoire and AbiE activity in Serratia

Phage Cocktails can Prevent the Evolution of Phage-ResistantEnterococcus

Prophage-encoded phage defense proteins with cognate self-immunity

Contact Info

Product

Resources

About