Tuesday’s #microtwjc (8pm GMT) will be looking at this paper:

The soft palate is an important site of adaptation for transmissible influenza viruses


Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells1, 2. Historically, influenza A viruses with preferential association withα2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets3, 4. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.



See you on Tuesday!!!


Tuesday’s #microtwjc (8pm GMT) will be looking at this paper:

Active Transport of Phosphorylated Carbohydrates Promotes Intestinal Colonization and Transmission of a Bacterial Pathogen

Brandon Sit , Shauna M. Crowley , Kirandeep Bhullar, Christine Chieh-Lin Lai, Calvin Tang, Yogesh Hooda, Charles Calmettes, Husain Khambati, Caixia Ma, John H. Brumell, Anthony B. Schryvers, Bruce A. Vallance , Trevor F. Moraes



Efficient acquisition of extracellular nutrients is essential for bacterial pathogenesis, however the identities and mechanisms for transport of many of these substrates remain unclear. Here, we investigate the predicted iron-binding transporter AfuABC and its role in bacterial pathogenesis in vivo. By crystallographic, biophysical and in vivo approaches, we show that AfuABC is in fact a cyclic hexose/heptose-phosphate transporter with high selectivity and specificity for a set of ubiquitous metabolites (glucose-6-phosphate, fructose-6-phosphate and sedoheptulose-7-phosphate). AfuABC is conserved across a wide range of bacterial genera, including the enteric pathogens EHEC O157:H7 and its murine-specific relative Citrobacter rodentium, where it lies adjacent to genes implicated in sugar sensing and acquisition. C. rodentium ΔafuA was significantly impaired in an in vivo murine competitive assay as well as its ability to transmit infection from an afflicted to a naïve murine host. Sugar-phosphates were present in normal and infected intestinal mucus and stool samples, indicating that these metabolites are available within the intestinal lumen for enteric bacteria to import during infection. Our study shows that AfuABC-dependent uptake of sugar-phosphates plays a critical role during enteric bacterial infection and uncovers previously unrecognized roles for these metabolites as important contributors to successful pathogenesis.

Author Summary

Essentially all Gram-negative pathogens are reliant on specific transport machineries termed binding protein-dependent transporters (BPDTs) to transport solutes such as amino acids, sugars and metal ions across their membranes. In this study we investigated AfuABC, a predicted iron-transporting BPDT found in many bacterial pathogens. We show by structural and functional approaches that AfuABC is not an iron transporter. Instead, AfuABC is a trio of proteins that bind and transport sugar-phosphates such as glucose-6-phosphate (G6P). In doing so, we present the first structural solution of a G6P-specific transport protein and add to the few known unique machineries for sugar-phosphate uptake by bacteria. Furthermore, we show that AfuABC is required by the intestinal pathogen C. rodentium to effectively transmit between mice and re-establish infection, leading us to propose that the transport of sugar-phosphates is an important part of general bacterial pathogenesis.


Discussion points to follow…

First and foremost, apologies for the late posting of this article! What with the rugby world cup and everything in work it has just been an immense couple of weeks.  But alas, the paper is here!

The paper has been chosen by myself (@sbi5ar) and will be discussed with the help of Nel (@helloitsnel).


A novel siderophore system is essential for the growth of Pseudomonas aeruginosa in airway mucus


Pseudomonas aeruginosa establishes airway infections in Cystic Fibrosis patients. Here, we investigate the molecular interactions between P. aeruginosa and airway mucus secretions (AMS) derived from the primary cultures of normal human tracheal epithelial (NHTE) cells. PAO1, a prototype strain of P. aeruginosa, was capable of proliferating during incubation with AMS, while
all other tested bacterial species perished. A PAO1 mutant lacking PA4834 gene became susceptible to AMS treatment. The ΔPA4834 mutant was grown in AMS supplemented with 100 μM ferric iron, suggesting that the PA4834 gene product is involved in iron metabolism. Consistently, intracellular iron content was decreased in the mutant, but not in PAO1 after the AMS treatment. Importantly,
a PAO1 mutant unable to produce both pyoverdine and pyochelin remained viable, suggesting that these two major siderophore molecules are dispensable for maintaining viability during incubation with AMS. The ΔPA4834 mutant was regrown in AMS amended with 100 μM nicotianamine, a phytosiderophore whose production is predicted to be mediated by the PA4836 gene. Infectivity of the ΔPA4834 mutant was also significantly compromised in vivo. Together, our results identify a genetic element encoding a novel iron acquisition system that plays a previously undiscovered role in P. aeruginosa airway infection.


1. Is this paper well written and easy to understand?

2. Does the introduction set the scene for the research presented?

3. Do the methods appear reliable and are they well explained?

4. Do the results and discussion make sense?

5. What (if any) future work could lead on from this?

In addition to these questions, hopefully we can explore whether the clinical significance that the paper portrays is justified though the research methods that have been used.

See you all next Tuesday (20th October 2015) at 20:00 (08:00 pm) BST

Hello Microtwjc community!

This week we are going to have a discussion on a recent article I have published with Laura Bowater (@Lauramcbow) and Paul Hoskisson (@PaulHoskisson) on engaging students on STEM degrees with the Antimicrobial Resistance issue. Yes this is not something we have discussed before as we have generally focussed on research papers. However, all of us at some point do interact with students at all levels. We are also interested to see what you all have to say on this subject….

You can find the paper here:

Inspiring STEM undergraduates to tackle the AMR crisis.

Things to discuss:

  1. Can you think of other ways to engage students on this topic?
  2. Do you have specific examples that would also work as case examples?
  3. Can we improve our engagement of under and post-graduates on topical issues within the learning environment?

See you all on twitter at 8 PM Tomorrow night!


Hello alls,

In under a week we will be running session #2 of #microtwjc for the 2015 academic year. The paper I (@id_EATER) chose with input from @defectivebrayne is titled:

A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity

It’s a pretty straight forward paper which details the preparation of an ancient antimicrobial recipe and some studies on it’s antimicrobial efficacy. Some of the authors are on twitter (@friendlymicrobe, @sbi5ar and @stevediggle) which means we may have the opportunity to ask them questions directly.

Please keep the following discussion points/questions in mind when reading the paper and feel free to tweet to @microtwjc or comment below with any points/questions you might have during reading as well as any question you might have for the authors directly.

  1. How does the introduction support the research and (in addition to the discussion) help contextualize the findings in the field?
  2. What are the advantages and limitations of the experimental models chosen to study the antimicrobial effect of Bald’s eyesalve?
  3. Are the conclusions supported by the data (methods and results) in the paper?
  4. What have we learnt after reading the paper?
  5. Given what we have learnt, what future work would be of interest to conduct?

Here’s the abstract and hope to see you online!

Plant-derived compounds and other natural substances are a rich potential source of compounds that kill or attenuate pathogens that are resistant to current antibiotics. Medieval societies used a range of these natural substances to treat conditions clearly recognizable to the modern eye as microbial infections, and there has been much debate over the likely efficacy of these treatments. Our interdisciplinary team, comprising researchers from both sciences and humanities, identified and reconstructed a potential remedy for Staphylococcus aureus infection from a 10th century Anglo-Saxon leechbook. The remedy repeatedly killed established S. aureus biofilms in an in vitro model of soft tissue infection and killed methicillin-resistant S. aureus (MRSA) in a mouse chronic wound model. While the remedy contained several ingredients that are individually known to have some antibacterial activity, full efficacy required the combined action of several ingredients, highlighting the scholarship of premodern doctors and the potential of ancient texts as a source of new antimicrobial agents.


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