Recent advances in phage defense systems and potential overcoming strategies

Yuan, Xiaoming; Huang, Zhichao; Zhu, Zhenan; Zhang, Jumei; Wu, Qingping; Li, Xue; Wang, Juan; Ding, Yu

doi:10.1016/j.biotechadv.2023.108152

Cited by 6 publications

(5 citation statements)

References 116 publications

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“…CRISPR-Cas systems exhibit variability, consisting of six types (I–VI) across two classes, totaling 50 subtypes based on their sequences [ 48 ]. Despite this diversity, two fundamental functions are conserved among the different types [ 49 ]. The first involves cas genes, which encode Cas proteins responsible for manipulating nucleic acids.…”

Section: Discussionmentioning

confidence: 99%

“…Functioning as adaptive immunity, the system’s adaptability is evident in acquiring spacers from invaders. These acquired spacers can undergo transcription to form small CRISPR RNAs (crRNAs) that, when combined with Cas nucleases, serve as a defense mechanism against foreign nucleic acids [ 49 ]. However, our discovery revealed additional methods of protection against leptophages, specifically, RM_Type_IV (also known as the type IV restriction–modification (R–M) system), PrrC, and Borvo ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…The R–M systems are categorized into four types. Types I–III include methyltransferases that methylate the host DNA and corresponding restriction endonucleases (RNases) that cleave invasive and unmethylated DNA [ 49 ]. In contrast, the type IV R–M system lacks methyltransferases and instead specifically recognizes methylated DNA.…”

Section: Discussionmentioning

confidence: 99%

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Exploring Leptospira interrogans FDAARGOS_203: Insights into AMR and Anti-Phage Defense

Petakh,

Oksenych,

Kamyshnyi

2024

Microorganisms

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Leptospira, which are known to be important disease-causing agents transmitted between animals and humans, result in significant illness and, in some cases, significant death in human populations. This purpose of this study was to examine the genomic structure of Leptospira interrogans serovar Copenhageni strain FDAARGOS_203 to identify the specific genetic factors that contribute to antimicrobial resistance (AMR) and defense against phages. The genome, consisting of two contigs totaling 4,630,574 base pairs, underwent thorough examination for protein-coding sequences, transfer RNA genes, and ribosomal RNA genes. A total of twenty-two antibiotic resistance genes that specifically target essential cellular processes such as cell wall synthesis, DNA replication, and protein synthesis have been identified. Significant among these were gidB, gdpD, and ggsA, each involved in separate aspects of antibiotic resistance. In addition, the investigation explored the defense mechanisms of bacteriophages, revealing the presence of defense islands that contain a range of anti-phage systems, including RM_Type_IV, PrrC, Borvo, CAS_Class1-Subtype-IC, and CAS_Class1-Subtype-IB. This comprehensive genomic analysis enhances our understanding of the molecular mechanisms that determine Leptospira’s ability to adapt to various environments. The identified genetic factors linked to AMR and defense against phages not only enhance our scientific comprehension, but also provide a basis for focused interventions to reduce the impact of leptospirosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Exploring Leptospira interrogans FDAARGOS_203: Insights into AMR and Anti-Phage Defense

Petakh,

Oksenych,

Kamyshnyi

2024

Microorganisms

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“…Considering the presence of leptophages, it is likely that leptospires should have appropriate natural protection systems against phages to limit phage infection ( Bernheim and Sorek, 2020 ). Guohui Xiao et al described the presence of the CRISPR–Cas system; however, as is known, microorganisms have a whole arsenal of defense systems against phages ( Xiao et al, 2019 ; Yuan et al, 2023 ). Antiphage defense systems exhibit a nonrandom distribution in microbial genomes, often forming “defense islands” where multiple systems cluster together ( Makarova et al, 2013 ; Doron et al, 2018 ; Hochhauser et al, 2023 ).…”

Section: Phage For Leptospirosis Treatmentmentioning

confidence: 99%

Current treatment options for leptospirosis: a mini-review

Petakh,

Behzadi,

Oksenych

et al. 2024

Front. Microbiol.

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Leptospirosis, one of the most common global zoonotic infections, significantly impacts global human health, infecting more than a million people and causing approximately 60,000 deaths annually. This mini-review explores effective treatment strategies for leptospirosis, considering its epidemiology, clinical manifestations, and current therapeutic approaches. Emphasis is placed on antibiotic therapy, including recommendations for mild and severe cases, as well as the role of probiotics in modulating the gut microbiota. Furthermore, novel treatment options, such as bacteriophages and newly synthesized/natural compounds, are discussed, and the findings are expected to provide insights into promising approaches for combating leptospirosis.

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“…Considering the presence of leptophages, it is likely that leptospires have appropriate natural protection systems against phages to limit phage infection [ 21 ]. Xiao et al described the presence of the CRISPR-Cas system; however, as is known, microorganisms have a large arsenal of defense systems against phages [ 22 , 23 ]. Antiphage defense systems exhibit a nonrandom distribution in microbial genomes, often forming “defense islands” where multiple systems cluster together [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Antiphage Defense Mechanisms: Serovar-Specific Patterns

Petakh,

Oksenych,

Khovpey

et al. 2024

Antibiotics

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Leptospirosis is a major zoonotic disease caused by pathogenic spirochetes in the genus Leptospira, affecting over a million people annually and causing approximately 60,000 deaths. Leptospira interrogans, a key causative agent, likely possesses defense systems against bacteriophages (leptophages), yet these systems are not well understood. We analyzed 402 genomes of L. interrogans using the DefenseFinder tool to identify and characterize the antiphage defense systems. We detected 24 unique systems, with CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated proteins), PrrC, Borvo, and Restriction-Modification (R-M) being the most prevalent. Notably, Cas were identified in all strains, indicating their central role in phage defense. Furthermore, there were variations in the antiphage system distribution across different serovars, suggesting unique evolutionary adaptations. For instance, Retron was found exclusively in the Canicola serovar, while prokaryotic Argonaute proteins (pAgo) were only detected in the Grippotyphosa serovar. These findings significantly enhance our understanding of Leptospira’s antiphage defense mechanisms. They reveal the potential for the development of serovar-specific phage-based therapies and underscore the importance of further exploring these defense systems.

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Recent advances in phage defense systems and potential overcoming strategies

Cited by 6 publications

References 116 publications

Exploring Leptospira interrogans FDAARGOS_203: Insights into AMR and Anti-Phage Defense

Exploring Leptospira interrogans FDAARGOS_203: Insights into AMR and Anti-Phage Defense

Current treatment options for leptospirosis: a mini-review

Comprehensive Analysis of Antiphage Defense Mechanisms: Serovar-Specific Patterns

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