Influenza pandemics occur unpredictably when zoonotic influenza viruses with novel antigenicity acquire the ability to transmit amongst humans¹. Host range breaches are limited by incompatibilities between avian virus components and the human host. Barriers include receptor preference, virion stability and poor activity of the avian virus RNA-dependent RNA polymerase in human cells². Mutants of the heterotrimeric viral polymerase components, particularly PB2 protein, are selected during mammalian adaptation, but their mode of action is unknown^3,4,5,6. We show that a species-specific difference in host protein ANP32A accounts for the suboptimal function of avian virus polymerase in mammalian cells. Avian ANP32A possesses an additional 33 amino acids between the leucine-rich repeats and carboxy-terminal low-complexity acidic region domains. In mammalian cells, avian ANP32A rescued the suboptimal function of avian virus polymerase to levels similar to mammalian-adapted polymerase. Deletion of the avian-specific sequence from chicken ANP32A abrogated this activity, whereas its insertion into human ANP32A, or closely related ANP32B, supported avian virus polymerase function. Substitutions, such as PB2(E627K), were rapidly selected upon infection of humans with avian H5N1 or H7N9 influenza viruses, adapting the viral polymerase for the shorter mammalian ANP32A. Thus ANP32A represents an essential host partner co-opted to support influenza virus replication and is a candidate host target for novel antivirals.

Staphylococcus aureus is a major community and nosocomial pathogen. Its ability to withstand multiple stress conditions and quickly develop resistance to antibiotics complicates the control of staphylococcal infections. Adaptation to lower temperatures is a key for the survival of bacterial species outside the host. Branched-chain α-keto acid dehydrogenase (BKD) is an enzyme complex that catalyzes the early stages of branched-chain fatty acid (BCFA) production. In this study, BKD was inactivated, resulting in reduced levels of BCFAs in the membrane of S. aureus . Growth of the BKD-inactivated mutant was progressively more impaired than that of wild-type S. aureus with decreasing temperature, to the point that the mutant could not grow at 12°C. The growth of the mutant was markedly stimulated by the inclusion of 2-methylbutyrate in the growth medium at all temperatures tested. 2-Methylbutyrate is a precursor of odd-numbered anteiso fatty acids and bypasses BKD. Interestingly, growth of wild-type S. aureus was also stimulated by including 2-methylbutyrate in the medium, especially at lower temperatures. The anteiso fatty acid content of the BKD-inactivated mutant was restored by the inclusion of 2-methylbutyrate in the medium. Fluorescence polarization measurements indicated that the membrane of the BKD-inactivated mutant was significantly less fluid than that of wild-type S. aureus . Consistent with this result, the mutant showed decreased toluene tolerance that could be increased by the inclusion of 2-methylbutyrate in the medium. The BKD-inactivated mutant was more susceptible to alkaline pH and oxidative stress conditions. Inactivation of the BKD enzyme complex in S. aureus also led to a reduction in adherence of the mutant to eukaryotic cells and its survival in a mouse host. In addition, the mutant offers a tool to study the role of membrane fluidity in the interaction of S. aureus with antimicrobial substances.

In alkaline conditions, Listeria monocytogenes cells develop higher proportions of branched-chain fatty acids (FAs), including more anteiso forms. In acid conditions, the opposite occurs. Reduced growth of pH-sensitive mutants at adverse pH (5.0/9.0) was alleviated by the addition of 2-methylbutyrate (an anteiso-FA precursor), suggesting that anteiso-FAs are important in adaptation to adverse pH. The balance between anteiso- and iso-FAs may be more important than changes in the amounts and/or degrees of saturation of FAs in pH adaptation.

SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide—a well-tolerated drug widely used in advanced prostate cancer—reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.

Background: Microbiological standards within pork slaughter processing plants in the European Union are currently governed by Commission Regulation (EC) 2073/2005, which describes detailed performance criteria at specific stages of the procedure (following carcass dressing and before chilling) for total viable counts (TVC), Enterobacteriaceae (EB) and Salmonella spp. In this study, 95 carcasses from an Irish pork slaughter plant were sampled by swabbing 100 cm² of surface at three sites (belly, ham, jowl) to examine the effects of eight processing stages (stunning, bleeding, scalding, singeing, polishing, evisceration, final inspection and chilling) on contamination levels. Results: TVC ranged from approximately 1.7–6.3 log cfu cm² during sampling. There were significant reductions in TVC for all sites after scalding and singeing (p < 0.05), whilst there was a significant increase in counts after polishing and evisceration (p < 0.05) compared with preceding stages. EB counts indicated hygienic weak points in the examined slaughter plant leading to faecal (cross)-contamination, with elevated counts after stunning, bleeding and evisceration (p < 0.05), compared with final counts after chilling. Conclusions: Although the bacterial numbers reported in this study may reflect specific plant practices and temporal influences, results show that contamination can be introduced at various steps in the process and highlight the importance of monitoring locations other than those required by legislation within the process. Monitoring can be used to establish baseline levels for high-risk stages specific to each plant and to assess the effectiveness of additional interventions.

Evidence of an association between added sugars (AS) and the risk of obesity has triggered public health bodies to develop strategies enabling consumers to manage their AS intake. The World Health Organisation (WHO) has strongly recommended a reduction of free sugars to 10% of total dietary energy (TE) and conditionally recommended a reduction to 5% TE to achieve health benefits. Despite food labelling being a policy tool of choice in many countries, there is no consensus on the mandatory addition of AS to the nutrition panel of food labels. An online survey was conducted to explore consumer ability to identify AS on food labels and to investigate consumer awareness of the WHO guidelines in relation to sugar intakes. The questionnaire was tested for participant comprehension using face-to-face interviews prior to conducting the online study. The online survey was conducted in Northern Ireland during May 2015 and was completed by a convenient sample of 445 subjects. Results showed that just 4% of respondents correctly classified 10 or more ingredients from a presented list of 13 items, while 65% of participants were unaware of the WHO guidelines for sugar intake. It may be timely to reopen dialogue on inclusion of AS on food product nutrition panels.