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Biology subjects

Sieber, R. N.

Publications and source records attributed to Sieber, R. N..

3 recordsLinked to original sources

Emergence and spread of SARS-CoV-2 variants from farmed mink to humans and back during the epidemic in Denmark, June-November 2020.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. However, the routes of transmission of the virus to, and from, the mink have been unclear. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. Detailed analysis of changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants with the Y435F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early in the outbreak. However, further introductions of the virus, by variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of viral genome data, we estimate, using a conservative approach, that about 17 separate examples of mink to human transmission occurred in Denmark but up to 59 such events (90% credible interval: (39-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using Bayesian methods. Using the latter approach, 136 jumps (90% credible interval: (117-164)) from humans to mink were found, which may underlie the farm-to-farm spread. Thus, transmission of SARS-CoV-2 from humans to mink, mink to mink, from mink to humans and between humans were all observed. (298 words) Author summaryIn addition to causing a pandemic in the human population, SARS-CoV-2 also infected farmed mink. In Denmark, after the first identification of infection in mink during June 2020, a decision was made in November 2020 to cull all the farmed mink. Within this outbreak, mink on 290 farms (out of about 1100 in the country) were found to have been infected. We showed, by analysis of the viruses from the mink, that the viruses on the farms were mainly of three different, but closely related, types (termed Clusters 2, 3 and 4) that shared certain distinctive features. Thus, we found that many outbreaks in mink resulted from transmission of the virus between mink farms. However, we identified that new introductions of other virus variants, presumably from infected humans, also occurred. Furthermore, we showed that spread of the virus from infected mink to humans also happened on multiple occasions. Thus, transmission of these viruses from humans to mink, mink to mink, from mink to humans and between humans were all observed. (172 words)

microbiology↗

Neutralisation of SARS-CoV-2 Omicron subvariants BA.2.86 and EG.5.1 by antibodies induced by earlier infection or vaccination

Highly mutated SARS-CoV-2 Omicron subvariant BA.2.86 emerged in July 2023. We investigated the neutralisation of isolated virus by antibodies induced by earlier infection or vaccination. The neutralisation titres for BA.2.86 were comparable to those for XBB.1 and EG.5.1, by antibodies induced by XBB.1.5 or BA.4/5 breakthrough infection or BA.4/5 vaccination.

immunology↗

Endogenous Staphylococcus aureus CRISPR-cas system limits phage proliferation and efficiently excises from the genome as part of the SCCmec cassette

CRISPR-Cas is an adaptive immune system that allows bacteria to inactivate mobile genetic elements. Approximately 50% of bacteria harbor CRISPR-cas, however in the human pathogen Staphylococcus aureus, CRISPR-cas loci are less common and often studied in heterologous systems. We analyzed the prevalence of CRISPR-cas in genomes of methicillin resistant Staphylococcus aureus (MRSA) isolated in Denmark. Only 2.9 % of the strains carried CRISPR-cas systems, but for strains of sequence type ST630 over half were positive. All CRISPR-cas loci were type III-A and located within the staphylococcal chromosomal cassette (SCCmec) type V(5C2&5) conferring {beta}-lactam resistance. Curiously, only 23 different CRISPR spacers were identified in 69 CRISPR-positive strains and almost identical SCCmec cassettes, CRISPR arrays and cas genes, are present in staphylococcal species other than aureus, suggesting that these were transferred horizontally. For the ST630 strain 110900, we demonstrate that the SCCmec cassette containing CRISPR-cas excises from the chromosome at high frequency. However, the cassette was not transferable under the conditions investigated. One of the CRISPR spacers targets a late gene in the lytic bacteriophage (phage) virus philPLA-RODI, and we show that the system protects against phage infection by reducing phage burst size. However, CRISPR-Cas can be overloaded or bypassed by CRISPR escape mutants. Our results imply that the endogenous type III-A CRISPR-Cas system in S. aureus is active against targeted phages, albeit with low efficacy. This suggests native S. aureus CRISPR-Cas offers only partial immunity, and in nature may work in tandem with other defense systems. ImportanceCRISPR-Cas is an adaptive immune system enabling bacteria and archaea to protect themselves against mobile genetic elements such as phages. In strains of Staphylococcus aureus, CRISPR-cas is rare, but when present, it is located within the SCCmec element encoding resistance to methicillin and other {beta}-lactam antibiotics. We show that the entire module is excisable, with almost identical versions found in different species of non-aureus staphylococci suggesting that the system only rarely acquires new spacers in S. aureus. Additionally, we show that in its endogenous form, the S. aureus CRISPR-Cas is active but inefficient against lytic phages, with phages being able to form escape mutants or overload the system. This leads us to propose that CRISPR-Cas in S. aureus offers only partial immunity in native systems, and so may work together with other defense systems to prevent phage-mediated killing.

microbiology↗