Microbial Biotechnology is 15! An adventure in journal parenting.

This year, 2022, Microbial Biotechnology (MBT) celebrates its 15th birthday. In journal terms, 15 is adulthood. It has been a privilege to develop the idea, launch the journal, nurture it in its infancy and stimulate and support it during its adolescence and early adulthood. The success of MBT - its growth over the last 4 years averaging > 30%, and the highest impact factor in the field, making it the leading research journal in applied microbiology/microbial biotechnology and the most attractive to publish in - gives us enormous pleasure and satisfaction, and not a little pride.

The darkest microbiome-a post-human biosphere.

Microbial technology is exceptional among human activities and endeavours in its range of applications that benefit humanity, even exceeding those of chemistry. What is more, microbial technologists are among the most creative scientists, and the scope of the field continuously expands as new ideas and applications emerge. Notwithstanding this diversity of applications, given the dire predictions for the fate of the surface biosphere as a result of current trajectories of global warming, the future of microbial biotechnology research must have a single purpose, namely to help secure the future of life on Earth. Everything else will, by comparison, be irrelevant. Crucially, microbes themselves play pivotal roles in climate (Cavicchioli et al., Nature Revs Microbiol 17: 569-586, 2019). To enable realization of their full potential in humanity's effort to survive, development of new and transformative global warming-relevant technologies must become the lynchpin of microbial biotechnology research and development. As a consequence, microbial biotechnologists must consider constraining their usual degree of freedom, and re-orienting their focus towards planetary-biosphere exigences. And they must actively seek alliances and synergies with others to get the job done as fast as humanly possible; they need to enthusiastically embrace and join the global effort, subordinating where necessary individual aspirations to the common good (the amazing speed with which new COVID-19 diagnostics and vaccines were developed and implemented demonstrates what is possible given creativity, singleness of purpose and funding). In terms of priorities, some will be obvious, others less so, with some only becoming revealed after dedicated effort yields new insights/opens new vistas. We therefore refrain from developing a priority list here. Rather, we consider what is likely to happen to the Earth's biosphere if we (and the rest of humanity) fail to rescue it. We do so with the aim of galvanizing the formulation and implementation of strategic and financial science policy decisions that will maximally stimulate the development of relevant new microbial technologies, and maximally exploit available technologies, to repair existing environmental damage and mitigate against future deterioration.

Microbiome Yarns: bacterial predators, tissue tropism and molecular decoys.

This Crystal Ball speculates on the potential of molecular decoys for prevention and therapy in infectious diseases. It is dedicated to the memory of Singh Chhatwal, who pioneered research on disguises and decoys produced by Streptococcus, and so much more.

COVID-19: long covid and its societal consequences.

COVID-19 is an acute, highly transmissible respiratory infection that is potentially lethal, but often mild, sometimes asymptomatic, especially in the young. However, it has become clear that, in some patients, there may be sequelae involving tissues other than the lung, resulting in other types of morbidity, and sometimes longer term consequences that are often termed 'long covid'. In this Lilliput, we summarize recent findings about COVID-19 sequelae, with a particular focus on long covid. We also discuss some of the long scars that COVID-19 and long covid will collectively leave on society that we term Societal Long Covid.

SARS-CoV-2 biology and variants: anticipation of viral evolution and what needs to be done.

The global propagation of SARS-CoV-2 and the detection of a large number of variants, some of which have replaced the original clade to become dominant, underscores the fact that the virus is actively exploring its evolutionary space. The longer high levels of viral multiplication occur - permitted by high levels of transmission -, the more the virus can adapt to the human host and find ways to success. The third wave of the COVID-19 pandemic is starting in different parts of the world, emphasizing that transmission containment measures that are being imposed are not adequate. Part of the consideration in determining containment measures is the rationale that vaccination will soon stop transmission and allow a return to normality. However, vaccines themselves represent a selection pressure for evolution of vaccine-resistant variants, so the coupling of a policy of permitting high levels of transmission/virus multiplication during vaccine roll-out with the expectation that vaccines will deal with the pandemic, is unrealistic. In the absence of effective antivirals, it is not improbable that SARS-CoV-2 infection prophylaxis will involve an annual vaccination campaign against 'dominant' viral variants, similar to influenza prophylaxis. Living with COVID-19 will be an issue of SARS-CoV-2 variants and evolution. It is therefore crucial to understand how SARS-CoV-2 evolves and what constrains its evolution, in order to anticipate the variants that will emerge. Thus far, the focus has been on the receptor-binding spike protein, but the virus is complex, encoding 26 proteins which interact with a large number of host factors, so the possibilities for evolution are manifold and not predictable a priori. However, if we are to mount the best defence against COVID-19, we must mount it against the variants, and to do this, we must have knowledge about the evolutionary possibilities of the virus. In addition to the generic cellular interactions of the virus, there are extensive polymorphisms in humans (e.g. Lewis, HLA, etc.), some distributed within most or all populations, some restricted to specific ethnic populations and these variations pose additional opportunities for/constraints on viral evolution. We now have the wherewithal - viral genome sequencing, protein structure determination/modelling, protein interaction analysis - to functionally characterize viral variants, but access to comprehensive genome data is extremely uneven. Yet, to develop an understanding of the impacts of such evolution on transmission and disease, we must link it to transmission (viral epidemiology) and disease data (patient clinical data), and the population granularities of these. In this editorial, we explore key facets of viral biology and the influence of relevant aspects of human polymorphisms, human behaviour, geography and climate and, based on this, derive a series of recommendations to monitor viral evolution and predict the types of variants that are likely to arise.

The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19.

The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.

COVID-19 transmission: economy-boosting investment should target innovation in pandemic containment strategies to minimize restrictions of civil liberties.

Imposition of restrictions on civil liberties in response to epi/pandemic crises provokes collateral health, economic and social crises. Moreover, as a result of the societal distress engendered, they become less effective over time, reflected in reducing acceptability, public protests, lack of compliance and civil disobedience, as evidenced by current events in some countries. There is an urgent need to evolve new containment strategies that minimize civil liberty restrictions. This requires strategic economic policies to invest in what might be termed pandemic containment innovation, particularly in the development of new means of reducing virus concentrations in closed spaces, and of precision exclusion of virus transmitters from public assemblies. Such innovations and their implementation will in turn create significant employment and boost economies. And, because such investments aim at increasing the resilience of society, healthcare and the economy to pandemics (and indeed outbreaks of respiratory infections in general), they are particularly sustainable.

Visualizing the invisible: class excursions to ignite children's enthusiasm for microbes.

We have recently argued that, because microbes have pervasive - often vital - influences on our lives, and that therefore their roles must be taken into account in many of the decisions we face, society must become microbiology-literate, through the introduction of relevant microbiology topics in school curricula (Timmis et al. 2019. Environ Microbiol 21: 1513-1528). The current coronavirus pandemic is a stark example of why microbiology literacy is such a crucial enabler of informed policy decisions, particularly those involving preparedness of public-health systems for disease outbreaks and pandemics. However, a significant barrier to attaining widespread appreciation of microbial contributions to our well-being and that of the planet is the fact that microbes are seldom visible: most people are only peripherally aware of them, except when they fall ill with an infection. And it is disease, rather than all of the positive activities mediated by microbes, that colours public perception of 'germs' and endows them with their poor image. It is imperative to render microbes visible, to give them life and form for children (and adults), and to counter prevalent misconceptions, through exposure to imagination-capturing images of microbes and examples of their beneficial outputs, accompanied by a balanced narrative. This will engender automatic mental associations between everyday information inputs, as well as visual, olfactory and tactile experiences, on the one hand, and the responsible microbes/microbial communities, on the other hand. Such associations, in turn, will promote awareness of microbes and of the many positive and vital consequences of their actions, and facilitate and encourage incorporation of such consequences into relevant decision-making processes. While teaching microbiology topics in primary and secondary school is key to this objective, a strategic programme to expose children directly and personally to natural and managed microbial processes, and the results of their actions, through carefully planned class excursions to local venues, can be instrumental in bringing microbes to life for children and, collaterally, their families. In order to encourage the embedding of microbiology-centric class excursions in current curricula, we suggest and illustrate here some possibilities relating to the topics of food (a favourite pre-occupation of most children), agriculture (together with horticulture and aquaculture), health and medicine, the environment and biotechnology. And, although not all of the microbially relevant infrastructure will be within reach of schools, there is usually access to a market, local food store, wastewater treatment plant, farm, surface water body, etc., all of which can provide opportunities to explore microbiology in action. If children sometimes consider the present to be mundane, even boring, they are usually excited with both the past and the future so, where possible, visits to local museums (the past) and research institutions advancing knowledge frontiers (the future) are strongly recommended, as is a tapping into the natural enthusiasm of local researchers to leverage the educational value of excursions and virtual excursions. Children are also fascinated by the unknown, so, paradoxically, the invisibility of microbes makes them especially fascinating objects for visualization and exploration. In outlining some of the options for microbiology excursions, providing suggestions for discussion topics and considering their educational value, we strive to extend the vistas of current class excursions and to: (i) inspire teachers and school managers to incorporate more microbiology excursions into curricula; (ii) encourage microbiologists to support school excursions and generally get involved in bringing microbes to life for children; (iii) urge leaders of organizations (biopharma, food industries, universities, etc.) to give school outreach activities a more prominent place in their mission portfolios, and (iv) convey to policymakers the benefits of providing schools with funds, materials and flexibility for educational endeavours beyond the classroom.

SARS-CoV-2 variants: Relevance for symptom granularity, epidemiology, immunity (herd, vaccines), virus origin and containment?

The origin of the SARS-CoV-2 virus remains enigmatic. It is likely to be a continuum resulting from inevitable mutations and recombination events. These genetic changes keep developing in the present epidemic. Mutations tending to deplete the genome in its cytosine content will progressively lead to attenuation as a consequence of Muller's ratchet, but this is counteracted by recombination when different mutants co-infect the same host, in particular, in clusters of infection. Monitoring as a function of time the genome sequences in closely related cases is critical to anticipate the future of SARS-CoV-2 and hence of COVID-19.