ORCID Profile
0000-0003-0527-0141
Current Organisations
Inselspital, Universitätsspital Bern
,
Technische Universiteit Delft
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 07-04-2017
Abstract: To repel infection by phage and mobile genetic elements, prokaryotes have a form of adaptive immune response and memory invested in clustered regularly interspaced short palindromic repeats and associated proteins (CRISPR-Cas). This molecular machinery can recognize and remember foreign nucleic acids by capturing and retaining small nucleotide sequences. On subsequent encounters, the cognate CRISPR-Cas marshals enzymatic defenses to destroy infecting elements that contain the same sequences. Jackson et al. review the molecular mechanisms by which erse CRISPR-Cas systems adapt and anticipate novel threats and evasive countermeasures from mobile genetic elements. Science , this issue p. eaal5056
Publisher: Oxford University Press (OUP)
Date: 28-02-2019
DOI: 10.1093/CID/CIZ164
Abstract: Human immunodeficiency virus (HIV)–positive gay and bisexual men (GBM) in Australia are well engaged in care. The World Health Organization’s (WHO) hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030 may be reachable ahead of time in this population. We predicted the effect of treatment and behavioral changes on HCV incidence among HIV-positive GBM up to 2025 using a HCV transmission model parameterized with Australian data. We assessed the impact of changes in behavior that facilitate HCV transmission in the context of different rates of direct-acting antiviral (DAA) use. HCV incidence in our model increased from 0.7 per 100 person-years in 2000 to 2.5 per 100 person-years in 2016 and had the same trajectory as previously reported clinical data. If the proportion of eligible (HCV RNA positive) patients using DAAs stays at 65% per year between 2016 and 2025, with high-risk sexual behavior and injecting drug use remaining at current levels, HCV incidence would drop to 0.4 per 100 person-years (85% decline from 2016). In the same treatment scenario but with substantial increases in risk behavior, HCV incidence would drop to 0.6 per 100 person-years (76% decline). If the proportion of eligible patients using DAAs dropped from 65% per year in 2016 to 20% per year in 2025 and risk behavior did not change, HCV incidence would drop to 0.7 per 100 person-years (70% reduction). Reaching the WHO HCV elimination target by 2025 among HIV-positive GBM in Australia is achievable.
Publisher: Informa UK Limited
Date: 14-03-2013
DOI: 10.4161/RNA.24046
Publisher: Cold Spring Harbor Laboratory
Date: 26-01-2019
DOI: 10.1101/527796
Abstract: Microbiomes are vast communities of microbes and viruses that populate all natural ecosystems. Viruses have been considered the most variable component of microbiomes, as supported by virome surveys and ex les of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared to other environments. Here we investigate the origin, evolution, and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboratory, we obtained DNA sequences of crAssphage from over one-third of the world's countries, and showed that its phylogeography is locally clustered within countries, cities, and in iduals. We also found colinear crAssphage-like genomes in both Old-World and New-World primates, challenging genomic mosaicism and suggesting that the association of crAssphage with primates may be millions of years old. We conclude that crAssphage is a benign globetrotter virus that may have co-evolved with the human lineage and an integral part of the normal human gut virome.
Publisher: Proceedings of the National Academy of Sciences
Date: 07-04-2014
Abstract: Bacteria are constantly exposed to foreign elements, such as bacteriophages and plasmids. The CRISPR-Cas (clustered regularly interspaced short palindromic repeats–CRISPR associated) adaptive immune systems provide heritable sequence-specific protection against these invaders. To develop immunity, bacteria add segments of foreign nucleic acid to their CRISPR memory. However, phage and plasmid mutants can evade CRISPR-Cas recognition by altering their targeted sequence. CRISPR-Cas responds to evasion by quickly generating immunity by acquiring new pieces of invader genome. We determined that this rapid generation of resistance is promiscuous, with recognition of highly erged or related elements eliciting new immunity. Our results demonstrate that CRISPR-Cas systems are more robust than previously thought and, not only have a highly specific resistance memory, but also have a broad ability to identify ergent genetic elements.
Publisher: Informa UK Limited
Date: 27-03-2013
DOI: 10.4161/RNA.24202
Publisher: Elsevier BV
Date: 05-2023
DOI: 10.1016/J.TIBTECH.2022.08.008
Abstract: In recent years, bacteriophage research has been boosted by a rising interest in using phage therapy to treat antibiotic-resistant bacterial infections. In addition, there is a desire to use phages and their unique proteins for specific biocontrol applications and diagnostics. However, the ability to manipulate phage genomes to understand and control gene functions, or alter phage properties such as host range, has remained challenging due to a lack of universal selectable markers. Here, we discuss the state-of-the-art techniques to engineer and select desired phage genomes using advances in cell-free methodologies and clustered regularly interspaced short palindromic repeats-CRISPR associated protein (CRISPR-Cas) counter-selection approaches.
Publisher: Springer Science and Business Media LLC
Date: 03-10-2016
DOI: 10.1038/NCOMMS12853
Abstract: CRISPR–Cas systems provide bacteria with adaptive immunity against foreign nucleic acids by acquiring short, invader-derived sequences called spacers. Here, we use high-throughput sequencing to analyse millions of spacer acquisition events in wild-type populations of Pectobacterium atrosepticum . Plasmids not previously encountered, or plasmids that had escaped CRISPR–Cas targeting via point mutation, are used to provoke naive or primed spacer acquisition, respectively. The origin, location and order of spacer acquisition show that spacer selection through priming initiates near the site of CRISPR–Cas recognition (the protospacer), but on the displaced strand, and is consistent with 3′–5′ translocation of the Cas1:Cas2-3 acquisition machinery. Newly acquired spacers determine the location and strand specificity of subsequent spacers and demonstrate that interference-driven spacer acquisition (‘targeted acquisition’) is a major contributor to adaptation in type I-F CRISPR–Cas systems. Finally, we show that acquisition of self-targeting spacers is occurring at a constant rate in wild-type cells and can be triggered by foreign DNA with similarity to the bacterial chromosome.
No related grants have been discovered for Luisa Salazar-Vizcaya.