Article
Virology
Laura Fernandez-Garcia, Thomas K. Wood
Summary: The overlap between phage-defense systems (PDs) and toxin/antitoxin systems (TAs) has become clear as new PDs are discovered, as both systems use similar means to reduce cellular metabolism. They both have members that deplete energetic compounds and nucleic acids, and inflict membrane damage. Additionally, both systems reduce host metabolism to limit phage propagation and interaction of multiple defense systems.
Article
Multidisciplinary Sciences
Fatema Calcuttawala, Rahul Shaw, Arpita Sarbajna, Moumita Dutta, Saptarshi Sinha, Sujoy K. Das Gupta
Summary: This study investigated the mechanism of mycobacteriophage infection in Mycobacterium smegmatis cells, revealing that high VapC may play a role in inducing apoptotic cell death in mycobacteria. The research demonstrated morphological and molecular changes indicative of apoptotic cell death caused by D29 infection.
Article
Multidisciplinary Sciences
Fatema Calcuttawala, Rahul Shaw, Arpita Sarbajna, Moumita Dutta, Saptarshi Sinha, Sujoy K. Das Gupta
Summary: The study found that infection by mycobacteriophages causes mycobacteria to undergo apoptotic cell death. Researchers observed the details of the infection process and the morphological and molecular changes associated with cell death using immunofluorescence and electron microscopy techniques.
Review
Microbiology
Michele LeRoux, Michael T. Laub
Summary: Toxin-antitoxin (TA) systems are ubiquitous genetic elements in bacteria that help defend against phage infections. The biological functions of TA systems are still unclear, but they are widespread and rapidly acquired or lost in bacterial genomes. This review discusses the evidence for phage defense mediated by TA systems and the coevolutionary battle between bacteria and phage.
ANNUAL REVIEW OF MICROBIOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Khushal Khambhati, Gargi Bhattacharjee, Nisarg Gohil, Gurneet K. Dhanoa, Antonia P. Sagona, Indra Mani, Nhat Le Bui, Dinh-Toi Chu, Janardhan Keshav Karapurkar, Su Hwa Jang, Hee Yong Chung, Rupesh Maurya, Khalid J. Alzahrani, Suresh Ramakrishna, Vijai Singh
Summary: Antibiotic resistance is a major threat to humanity, and the use of bacteriophages as an alternative to antibiotics has gained interest. CRISPR-Cas9-assisted phage engineering provides a more specific targeting of bacterial pathogens. Techniques to enhance the fitness, specificity, and lytic ability of phages can be used to control infections.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Microbiology
Cas Mosterd, Sylvain Moineau
Summary: The Streptococcus mutans strain P42S possesses a type II-A CRISPR-Cas system that protects against phage infection and plasmid transformation. Analysis of bacteriophage-insensitive mutants (BIMs) revealed the acquisition of unique spacers, including ectopic acquisitions and native spacer deletions. Further study on this system provides new insights into spacer acquisition, PAM recognition, multiple-spacer acquisition, and priming mechanisms.
Article
Cell Biology
Sonia Jain, Arghya Bhowmick, Bohyun Jeong, Taeok Bae, Abhrajyoti Ghosh
Summary: This study investigates the impact of the mazEF toxin-antitoxin module on biofilm formation, pathogenesis, and antibiotic resistance in a clinical MRSA strain. The study showed that the activated MazF toxin promotes cell death and lysis for biofilm formation and leads to resistance to antibiotics like oxacillin, daptomycin, and vancomycin.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Microbiology
Muyang Ni, Jianzhong Lin, Jiayu Gu, Shituan Lin, Mei He, Yunxue Guo
Summary: The bacterial pathogen Pseudomonas aeruginosa has a toxin-antitoxin (TA) system consisting of the antitoxin CrlA and the toxin CrlT. CrlA neutralizes the toxicity of CrlT and inhibits infection by Pseudomonas phages. This TA system is induced in the stationary phase and may provide antiphage activities.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Michael Parcey, Steven Gayder, Alan J. Castle, Antonet M. Svircev
Summary: This study analyzed recently published genomes to find that two significant groups of E. amylovora are poorly identified using current CRISPR-based tracking methods. The study also demonstrated that the CRISPR-Cas system and an unidentified mechanism work together to provide a significant degree of resistance against one of the phages proposed for phage-based biocontrol.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yu Chen, Zhifeng Zeng, Qunxin She, Wenyuan Han
Summary: CRISPR-Cas and pAgo are defense systems in prokaryotes that use nucleic acid (NA) guides to recognize and cleave invading NA targets. However, they also utilize the abortive infection (Abi) strategy to activate toxic effectors and kill infected cells, preventing the spread of invaders. This review summarizes the mechanisms of CRISPR-Cas and pAgo systems and highlights their crucial roles in the microbial arms race against invaders.
TRENDS IN MICROBIOLOGY
(2023)
Article
Microbiology
Laura Fernandez-Garcia, Sooyeon Song, Joy Kirigo, Michael E. Battisti, Maiken E. Petersen, Maria Tomas, Thomas K. Wood
Summary: This study reveals that bacteria can defend against phage infection by forming persister cells instead of inducing cell suicide. Furthermore, the restriction/modification systems work together with the toxin/antitoxin system to clear phage DNA. These findings are crucial for the success of phage therapy.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biotechnology & Applied Microbiology
Shayna R. Deecker, Malene L. Urbanus, Beth Nicholson, Alexander W. Ensminger
Summary: Legionella pneumophila, the causative agent of Legionnaires' disease, maintains active CRISPR-Cas defenses targeting an episomal element named Legionella mobile element 1 (LME-1). Additional LME-1 variants have been identified as well. Furthermore, CRISPR-Cas spacers with sequence similarity to microviruses within the Gokushovirinae subfamily have been found, suggesting recurrent encounters with these phages.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Engineering, Environmental
Zhuodong Yu, Cory Schwarz, Liang Zhu, Linlin Chen, Yun Shen, Pingfeng Yu
Summary: The study demonstrates that the lytic coliphage PHHO1 can hitchhike on carrier bacteria Bacillus cereus to infect host bacteria more effectively in biofilms. This mutualistic relationship enhances bacterial colonization, influences biofilm composition, and has the potential to mediate biofilm functions and moderate associated risks.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alfred Fillol-Salom, Jakob T. Rostol, Adaeze D. Ojiogu, John Chen, Gill Douce, Suzanne Humphrey, Jose R. Penades
Summary: This study discovers a important anti-phage system in bacteria called phage-inducible chromosomal islands (PICIs), which can be disseminated intra-and inter-generically by helper phages and provide broad immunity. Results show that phages can mobilize PICI-encoded immunity systems to use them against other mobile genetic elements, which compete with the phages for the same bacterial hosts. This finding has significant implications for phages, bacteria, and horizontal gene transfer control.
Article
Microbiology
Stephen Dela Ahator, Sadhanna Sagar, Minya Zhu, Jianhe Wang, Lian-Hui Zhang
Summary: Quorum sensing (QS) and CRISPR-Cas systems play vital roles in bacterial survival and defense against phages, and their dynamics are influenced by environmental factors. Understanding the impact of environmental factors on bacterial communities and phage defense mechanisms driven by QS and CRISPR-Cas systems is crucial for the development of effective phage therapy.
Article
Biochemistry & Molecular Biology
Lucia M. Malone, Hannah G. Hampton, Xochitl C. Morgan, Peter C. Fineran
Summary: The study revealed that phage infection alters bacterial metabolism and responses. While the CRISPR-Cas system provides effective defense against viruses, viruses still have an impact on bacterial hosts. Additionally, the study found that the CRISPR immunity mechanism within infected cells can activate specific feedback regulatory loops.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Rafael Pinilla-Redondo, Jakob Russel, David Mayo-Munoz, Shiraz A. Shah, Roger A. Garrett, Joseph Nesme, Jonas S. Madsen, Peter C. Fineran, Soren J. Sorensen
Summary: Research shows that CRISPR-Cas systems are common accessory components of many plasmids, with plasmid CRISPRs displaying a strong targeting bias towards other plasmids, while chromosomal arrays are enriched with virus-targeting spacers, highlighting the genetic independence of plasmids and suggesting a major role in mediating plasmid-plasmid conflicts.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Nils Birkholz, Simon A. Jackson, Robert D. Fagerlund, Peter C. Fineran
Summary: Epigenetic DNA methylation plays a crucial role in bacteria, influencing gene expression and protecting host DNA. The interaction between restriction-modification systems and restriction endonucleases depends on DNA methylation. However, the impact of mobile defence systems on pre-existing host defences is not well understood. This study reveals an epigenetic conflict between an RM system and a methylation-dependent REase in a plant pathogen, highlighting the selfishness and intracellular competition of different defence mechanisms.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Evan A. Schwartz, Tess M. McBride, Jack P. K. Bravo, Daniel Wrapp, Peter C. Fineran, Robert D. Fagerlund, David W. Taylor
Summary: This study reveals the specific binding ability of type I-D Cascade to ssRNA and the structural rearrangements initiated by PAM recognition of dsDNA targets. It also models how the anti-CRISPR protein blocks target dsDNA binding.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
So Yeon Lee, Nils Birkholz, Peter C. Fineran, Hyun Ho Park
Summary: CRISPR-Cas systems are bacterial defense systems that fight against invaders. Phages have evolved multiple anti-CRISPR proteins to escape destruction by these systems. Aca10 is a recently discovered Aca protein that acts as a transcriptional repressor in the acrIC7-acrIC6-aca10 operon and binds to specific DNA sequences.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Leighton J. Payne, Sean Meaden, Mario R. Mestre, Chris Palmer, Nicolas Toro, Peter C. Fineran, Simon A. Jackson
Summary: Most bacteria and archaea possess multiple antiviral defence systems, and the PADLOC web server provides a convenient resource for analyzing and detecting these systems.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Saadlee Shehreen, Nils Birkholz, Peter C. Fineran, Chris M. Brown
Summary: Many bacteria use CRISPR-Cas systems to defend against invasive mobile genetic elements, and in response, these genetic elements have developed strategies to resist CRISPR-Cas. This study identified and analyzed Aca and AcrIIA1 homologs in bacterial genomes and demonstrated the widespread conservation of Aca proteins in repressing acr expression.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biotechnology & Applied Microbiology
Marina Mahler, Ana Rita Costa, Sam P. B. van Beljouw, Peter C. Fineran, Stan J. J. Brouns
Summary: In recent years, there has been increasing interest in using phage therapy to treat antibiotic-resistant bacterial infections, which has boosted bacteriophage research. There is also a desire to use phages and their unique proteins for specific biocontrol applications and diagnostics. However, manipulating phage genomes to understand and control gene functions, as well as altering phage properties such as host range, has been challenging due to a lack of universal selectable markers.
TRENDS IN BIOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Tess M. McBride, Shaharn C. Cameron, Peter C. Fineran, Robert D. Fagerlund
Summary: Prokaryotes have adaptive defence mechanisms called CRISPR-Cas systems to protect them from mobile genetic elements and viral infection. Type I and III systems utilize multi-protein complexes, while the type I-D system is a chimera of type I and III systems. This review focuses on the mechanism, evolution, and biotechnological applications of the type I-D CRISPR-Cas system.
BIOCHEMICAL JOURNAL
(2023)
Article
Genetics & Heredity
Marina Mahler, Lucia M. Malone, Daan F. van den Berg, Leah M. Smith, Stan J. J. Brouns, Peter C. Fineran
Summary: In this study, a newly isolated phage LC53 infecting Serratia sp. ATCC 39006 was characterized. LC53 showed morphological, phenotypic, and genomic similarities to other Serratia, Erwinia, and Kosakonia phages belonging to the Winklervirus genus. The host ompW gene was identified as essential for phage infection, suggesting that it encodes the phage receptor. LC53's genome encodes all the characteristic T4-like core proteins involved in phage DNA replication and viral particle generation. In addition, LC53 has a similar transcriptional organization to Escherichia coli phage T4 and contains 18 tRNAs that likely compensate for differences in GC content between phage and host genomes. Overall, this study expands the diversity of phages available for studying phage-host interactions.
MICROBIAL GENOMICS
(2023)
Article
Microbiology
Heather L. Shearer, Paul E. Pace, Leah M. Smith, Peter C. Fineran, Allison J. Matthews, Andrew Camilli, Nina Dickerhof, Mark B. Hampton
Summary: By using saturation transposon mutagenesis and deep sequencing, this study identified 37 genes associated with hypothiocyanous acid (HOSCN) tolerance in Streptococcus pneumoniae. These genes are involved in metabolism, membrane transport, DNA repair, and oxidant detoxification. Validation experiments showed that most of the single-gene deletion mutants exhibited increased sensitivity to HOSCN, and some mutants showed enhanced activity of antioxidant defense systems. The double deletion of glutathione reductase and sodA significantly sensitized the bacteria. The HOSCN defense systems identified in this study may serve as viable targets for novel therapeutics against S. pneumoniae.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Multidisciplinary Sciences
Sarah Camara-Wilpert, David Mayo-Munoz, Jakob Russel, Robert D. Fagerlund, Jonas S. Madsen, Peter C. Fineran, Soren J. Sorensen, Rafael Pinilla-Redondo
Summary: Many bacteria use CRISPR-Cas systems to fight against mobile genetic elements like bacteriophages and plasmids. In response, these invasive elements have developed anti-CRISPR proteins to block host immunity. We have discovered a new type of CRISPR-Cas inhibition strategy based on small non-coding RNA anti-CRISPRs. These RNAs mimic the repeats found in CRISPR arrays and are encoded as individual repeat units in viral genomes. They strongly inhibit the type I-F CRISPR-Cas system by interacting with specific Cas proteins, leading to the formation of abnormal Cas subcomplexes.
Article
Biochemistry & Molecular Biology
Benjamin A. Adler, Marena Trinidad, Daniel Bellieny-Rabelo, Elaine Zhang, Hannah M. Karp, Petr Skopintsev, Brittney W. Thornton, Rachel F. Weissman, Peter H. Yoon, Linxing Chen, Tomas Hessler, Amy R. Eggers, David Colognori, Ron Boger, Erin E. Doherty, Connor A. Tsuchida, Ryan Tran, Laura Hofman, Honglue Shi, Kevin M. Wasko, Zehan Zhou, Chenglong Xia, Muntathar J. Al-Shimary, Jaymin R. Patel, Vienna C. J. X. Thomas, Rithu Pattali, Matthew J. Kan, Anna Vardapetyan, Alana Yang, Arushi Lahiri, Michaela F. Maxwell, Andrew G. Murdock, Glenn C. Ramit, Hope R. Henderson, Roland W. Calvert, Rebecca S. Bamert, Gavin J. Knott, Audrone Lapinaite, Patrick Pausch, Joshua C. Cofsky, Erik J. Sontheimer, Blake Wiedenheft, Peter C. Fineran, Stan J. J. Brouns, Dipali G. Sashital, Brian C. Thomas, Christopher T. Brown, Daniela S. A. Goltsman, Rodolphe Barrangou, Virginius Siksnys, Jillian F. Banfield, David F. Savage, Jennifer A. Doudna
Summary: CRISPR-Cas enzymes play a crucial role in bacterial immunity and genome editing. CasPEDIA is a comprehensive database that summarizes the enzymatic properties of Cas enzymes, providing valuable resources for researchers.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Leah M. Smith, Hannah G. Hampton, Mariya S. Yevstigneyeva, Marina Mahler, Zacharie S. M. Paquet, Peter C. Fineran
Summary: Bacteria protect themselves from infection by bacteriophages using different defence systems, such as CRISPR-Cas. However, these defence systems also come with fitness costs. In this study, PigU is identified as a major regulator of CRISPR-Cas immunity in Serratia, and it shuts off CRISPR-Cas interference against phages and plasmids by repressing its expression.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Microbiology
Alfonso Lopez-Rojo, Simon A. Jackson, Diego Bernal-Bernal, Marisa Galbis-Martinez, Peter C. Fineran, Montserrat Elias-Arnanz
Summary: This study focused on Myxococcus xanthus and its bacteriophages, revealing complete genomes of Mx1 and a widely used Mx4 derivative, both classified as Caudoviricetes with long tails.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2023)
