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Since 2003, highly pathogenic avian influenza (HPAI) viruses of the H5 subtype have been maintained in poultry, periodically spilling back into wild migratory birds and spread to other geographic regions, with re-introduction to domestic birds causing severe impacts for poultry health, production and food sustainability. Successive waves of infection have also resulted in substantial genetic evolution and reassortment, enabling the emergence of multiple clades and subtypes within the H5 2.3.4.4 HPAI viruses. Control of AI is principally through either culling or through vaccination using conventional vaccines. Here, we antigenically and genetically characterise the emerging 2020/21 H5NX clade 2.3.4.4 strains and assess cross-reactivity to putative vaccine strains using chicken antisera. We demonstrate significant antigenic differences between commercially available poultry vaccines and currently circulating viruses suggesting that vaccination options might be suboptimal in the current outbreaks.

Analyses of HPAI H5 viruses from poultry outbreaks across a wide Eurasian region since July 2020 including the Russian Federation, Republics of Iraq and Kazakhstan, and recent detections in migratory waterfowl in the Netherlands, revealed undetected maintenance of H5N8, likely in galliform poultry since 2017/18 and both H5N5 and H5N1. All viruses belong to A/H5 clade 2.3.4.4b with closely related HA genes. Heterogeneity in Eurasian H5Nx HPAI emerging variants threatens poultry production, food security and veterinary public health.

We report a disease and mortality event involving swans, seals, and a fox at a wildlife rehabilitation center in the United Kingdom during late 2020. Five swans had onset of highly pathogenic avian influenza virus infection while in captivity. Subsequently, 5 seals and a fox died (or were euthanized) after onset of clinical disease. Avian-origin influenza A virus subtype H5N8 was retrospectively determined as the cause of disease. Infection in the seals manifested as seizures, and immunohistochemical and molecular testing on postmortem samples detected a neurologic distribution of viral products. The fox died overnight after sudden onset of inappetence, and postmortem tissues revealed neurologic and respiratory distribution of viral products. Live virus was isolated from the swans, seals, and the fox, and a single genetic change was detected as a potential adaptive mutation in the mammalian-derived viral sequences. No human influenza-like illness was reported in the weeks after the event

Phage therapy recently passed a key milestone with success of the first regulated clinical trial using systemic administration. In this single-arm non-comparative safety study, phages were administered intravenously to patients with invasive Staphylococcus aureus infections with no adverse reactions reported. Here, we examined features of 78 lytic S. aureus phages, most of which were propagated using a S. carnosus host modified to be broadly susceptible to staphylococcal phage infection. Use of this host eliminates the threat of contamination with staphylococcal prophage — the main vector of S. aureus horizontal gene transfer. We determined the host range of these phages against an international collection of 185 S. aureus isolates with 56 different multilocus sequence types that included multiple representatives of all epidemic MRSA and MSSA clonal complexes. Forty of our 78 phages were able to infect > 90% of study isolates, 15 were able to infect > 95%, and two could infect all 184 clinical isolates, but not a phage-resistant mutant generated in a previous study. We selected the 10 phages with the widest host range for in vitro characterization by planktonic culture time-kill analysis against four isolates:- modified S. carnosus strain TM300H, methicillin-sensitive isolates D329 and 15981, and MRSA isolate 252. Six of these 10 phages were able to rapidly kill, reducing cell numbers of at least three isolates. The four best-performing phages, in this assay, were further shown to be highly effective in reducing 48 h biofilms on polystyrene formed by eight ST22 and eight ST36 MRSA isolates. Genomes of 22 of the widest host-range phages showed they belonged to the Twortvirinae subfamily of the order Caudovirales in three main groups corresponding to Silviavirus, and two distinct groups of Kayvirus. These genomes assembled as single-linear dsDNAs with an average length of 140 kb and a GC content of c. 30%. Phages that could infect > 96% of S. aureus isolates were found in all three groups, and these have great potential as therapeutic candidates if, in future studies, they can be formulated to maximize their efficacy and eliminate emergence of phage resistance by using appropriate combinations.

Background Several outbreaks of highly pathogenic avian influenza (HPAI) caused by influenza A virus of subtype H5N8 have been reported in wild birds and poultry in Europe during autumn 2020. Norway is one of the few countries in Europe that had not previously detected HPAI virus, despite widespread active monitoring of both domestic and wild birds since 2005. Results We report detection of HPAI virus subtype H5N8 in a wild pink-footed goose (Anser brachyrhynchus), and several other geese, ducks and a gull, from south-western Norway in November and December 2020. Despite previous reports of low pathogenic avian influenza (LPAI), this constitutes the first detections of HPAI in Norway. Conclusions The mode of introduction is unclear, but a northward migration of infected geese or gulls from Denmark or the Netherlands during the autumn of 2020 is currently our main hypothesis for the introduction of HPAI to Norway. The presence of HPAI in wild birds constitutes a new, and ongoing, threat to the Norwegian poultry industry, and compliance with the improved biosecurity measures on poultry farms should therefore be ensured. [MK1]Finally, although HPAI of subtype H5N8 has been reported to have very low zoonotic potential, this is a reminder that HPAI with greater zoonotic potential in wild birds may pose a threat in the future. [MK1]Updated with a sentence emphasizing the risk HPAI pose to poultry farms, both in the Abstract and in the Conclusion-section in main text, as suggested by Reviewer 1 (#7).

Pseudomonas aeruginosa is a ubiquitous environmental microorganism that is also a common cause of nosocomial infections that vary in severity from chronic wound infections to pneumonia, bloodstream infections and sepsis. Its ability to survive in many different environments and persistently colonize human tissue is linked to its presence within biofilms that form on indwelling device surfaces such as plastics and stainless steel. Biofilm promotes bacterial adhesion and survival on surfaces, reduces susceptibility to desiccation, and the actions of antibiotics and disinfectants. Recent genome sequencing studies demonstrate that P. aeruginosa is a highly diverse species with a very large pan-genome consistent with its adaptability to differing environments. However, most MDR infections are caused by a small number of “high-risk” clones or lineages that recently emerged and spread globally.In our 2017 study of the resistome of P. aeruginosa we confirmed the power of genome-wide association (GWAS) techniques to explore the genetic basis of several antibiotic resistance phenotypes and discovered 46 novel putative resistance polymorphisms. In this study we sought to examine genetic associations within a subset of these isolates with simple biofilm phenotypes. We examined the genetic basis for biofilm production on polystyrene at room temperature (22°C) and body temperature (37°C) within a total of 280 isolates. 69% of isolates (n=193) produced more biofilm mass at 22°C, whilst those producing more biofilm at 37°C had reduced optical density 540 variation. We found statistically significant associations with IpxO and other genes associated with arsenic resistance to be significantly associated with this trait. IpxO which encodes a lipid A hydroxylase and arsenic reduction genes have previously been found to be associated with biofilm production in this species. We analyzed 260 ST111 and ST235 genomes and found considerable genetic variation between isolates in their content of genes previously found associated with biofilm production. This is indicative of a highly variable and flexible population within these clades with frequent emergence of successful sub-lineages. Analysis of 48 of these isolates’ ability to form biofilm on stainless steel surfaces showed that a ‘good’ biofilm-forming phenotype had significant intra-clone variation, independent of core genome phylogeny with pan-genome analysis, suggesting a possible association and involvement of components of the type IV secretion system. However, GWAS and pan-GWAS analyses yielded weaker statistical significance. This study confirms GWAS and pan-GWAS trait associations can be performed for biofilm phenotype and produce data in agreement with each other. This panel of 280 study isolates, matched to genomic data has potential for the investigation of other phenotypes in P. aeruginosa perhaps as part of a growing database / collection. A representative, curated, genome sequenced collection should increase in usefulness as it grows offering increasing statistical power.ImportanceP. aeruginosa is a major cause of multiply antibiotic infections worldwide but it is also found in many hospital and natural environments, especially aquatic ones. In this study we examined genetic polymorphism associated with biofilm production at room temperature and at body temperature, the biofilm associated gene repertoire of two major MDR clones and also genetic polymorphisms associated with biofilm production on stainless steel. Using these genome-wide and pan-genome wide association methods we identified / confirmed potential key genes involved in biofilm production and survival of P. aeruginosa. The study demonstrates the potential usefulness of large, genome sequenced isolate collections such as ours, to better understand the genetics underlying phenotypic diversity in this species.