Let microorganisms do the talking, let us talk more about microorganisms
© The Author(s) 2016
Received: 17 June 2016
Accepted: 21 June 2016
Published: 21 July 2016
Microorganisms are of uttermost importance, yet in the eyes of the general public they are often associated with dirt and diseases. At the same time, microbiologists have access to and comprehensive knowledge of just a tiny minority of the microbial diversity existing in nature. In this commentary, we present these issues of public misconception and scientific limitations and their possible consequences, and propose ways to overcome them. A particular interest is directed toward the secondary metabolism of filamentous fungi as well as novel outreach activities, including so-called “science slams” and interactions between the arts and the sciences, to raise awareness about the relevance of microorganisms.
KeywordsMicroorganisms Antibiotics crisis Microbial secondary metabolism Filamentous fungi Co-cultivation assays Science outreach Science slams “Art & science”
You’ve got to respect microbes. Not because “they are the only culture some people have,” as the comedian Steven Wright puts it. Neither are we talking about a reverential awe, fuelled by recurrent news of killer bugs and pandemic threats. Yes, microbes can be dangerous and can spread diseases easily around the globe. We are occasionally unable to tame them, as recent outbreaks of Ebola or Zika viruses [1, 2] as well as of devastating plant pathogens testify . And despite them being considered the simplest life form on earth, we still don’t know microbes as well as we need to. But in this lies also the beauty of them: in many regards, microorganisms are nature’s treasure trove awaiting to be opened.
The respect we are referring to is related to a fascination for microbes. Studies on microorganisms paved the way for crucial advances in major pillars of our modern society as medicine, human welfare [4–8], industry [9–11] and research [12, 13]. Some environmental species can break down or assimilate toxic compounds or pollutants and are useful in bioremediation [14, 15]. Microorganisms like Escherichia coli, Saccharomyces cerevisiae and Neurospora crassa have been the workhorses of molecular biology and playgrounds for scientific and technological breakthroughs [13, 16, 17]; recent discoveries on the “immune system” of streptococci  are currently used as CRISPR/Cas technology to edit genomes across all domains of life, including human zygotes  and embryos , and fuelling an ongoing scientific revolution [21, 22]. And yet, if at the basis of respect lies understanding, there are still lacunae to overcome—as much for the general public as for biologists or scientists themselves.
Microbiologists: the hipsters among scientists
These culture-dependent methods are microbiology’s double-edged sword. When they succeed in growing a new strain and in studying it in the laboratory, microbiologists alienate it from its natural habitat: in nature, microbes are highly promiscuous and most likely never grow axenically and in homogeneous substrata. To give a rough idea, a gram of soil harbours an estimate of 109 microbial cells and 1000 different species [28, 29]. The microbial diversity on us (e.g. the skin) and within our body (e.g. the gut) is similarly stunning: microorganisms outnumber our own cells (by a factor of up to ten according to some estimate [30–32]), so that humans are often referred as “superorganisms”. The positive effect of the human microbiome for the health of animals and plants is increasingly acknowledged, even if still poorly understood [33–35]. Similarly, the microbial community context should no longer be overlooked when investigating microbial pathogenesis, a goal that could be achieved by revisiting the classical Koch’s postulates .
Overcoming microbiologists’ culture-dependent limitations
Several protocols successfully overcome some limitations in microbiological methods. It’s now possible to cultivate cells in situ, inoculate them in controlled model systems, recreate natural conditions in the lab as well as grow mixed cultures instead of axenic ones or directly analyse chemical exchanges among microorganisms by mass spectrometry [37–43]. Yet during experiments with standard and reproducible conditions (a prerequisite for scientific consistency) some kind of complexity is invariably lost, and co-cultivation studies with as few as three species are cumbersome and extremely rare .
Some interactions amongst microorganisms are known and well characterised, as for example in intra-species communications (e.g. in the processes of quorum sensing  or biofilm formation [45, 46]) or in ecologically relevant, positive bipartite partnerships like lichens or mycorrhiza [47–49]. Other examples of associations involving microorganisms are those with marine sponges  or within the digestive tract of animals . Due to the complexity and inaccessibility of those microbiomes and habitats, however, the same drawbacks as outlined above exist (in particular, cultivation of the microbes and establishment of model systems to investigate them in the laboratory). For the overwhelming majority of cases, therefore, microorganisms cohabitate the same niche and/or host, and we don’t have any clue which kind of interactions they undergo—like anonymous neighbours in a multistory building who occasionally (if at all) greet each other on the stairway.
Secondary metabolism with primary significance
Related to this is the fact that, even for well-known industrial organisms studied and exploited for decades like the filamentous ascomycete Aspergillus niger, there is a so-called “secondary metabolism” which is mostly inactive under industrially used conditions and axenic growth [52–54]. This metabolism is required for “secondary” roles (e.g. to adapt to stress conditions and the presence of competitors [55, 56]), and it is consequently silent in the controlled settings of a research laboratory or fermentation process. Microbial secondary metabolites with antibiotic, anti-tumoral, psychotropic, cytotoxic, anti-cholesterol or immunosuppressant properties have been isolated [57, 58]. The interest of the microbial secondary metabolism for medicine and biotechnology is undisputed.
Cell-to-cell communication among microbes is investigated as a potent stimulus to activate their silent secondary metabolism [59–64]. When cells are competing with their neighbours for space or resources, they secrete secondary metabolites to engage in a chemical warfare. There seems to be a correlation between microbial promiscuity and ability to secrete secondary metabolites, as exemplified from the fact that soil microorganisms are the primary source of antibiotics [65, 66]. Nonetheless, microorganisms dwelling in scarcely inhabited regions like Antarctica produce antimicrobials as well  and these niches should be considered as well when hunting for new putative drug-producing strains.
Antibiotic resistance is on the rise [68–71] and since the last two decades no new class of antimicrobial has been developed . The shadow of a “pre-antibiotic” era does not belong to a distant past but might return as a considerable threat, and new antimicrobials are urgently sought after. Taken together, the need for new antibiotics, compounded by our inability to grow many microorganisms, leads the exploitation of microbial secondary metabolism in natural niches an important experimental goal.
Filamentous fungi as the workhorses of biotechnology
Among microorganisms, filamentous fungi hold great promises for biotechnology and medicine. In particular, their metabolic and physiological versatility along with their intrinsic resistance toward physical and chemical stresses makes them unequalled among other biotechnologically-relevant microorganisms [73–75]. Recent advances in molecular biology, “-omics” techniques and synthetic biology allowed a better understanding of the molecular cell biology of industrial relevant filamentous fungi, as for example members of the genus Aspergillus, making them attractive as microbial cell factories . Having entered the post-genomic era, new exciting possibilities arise for fungal biology [77, 78]. Such knowledge, however, has not been matched by advances in microbiological techniques [27, 79], a reason why the natural way of living of microorganisms is still obscure and this nature’s treasure trove—microbes themselves as well as the secondary metabolism of well-known species—is mostly shut.
We argue that new cultivation techniques are necessary to activate the silent secondary metabolism of filamentous fungi, and, in particular, that co-cultivation experiments under natural conditions (in situ setting) are greatly implementable. One way to do this might be the convergence of existing approaches into a single laboratory tool. The effects of microbial cross-talk in nature might be better exploited by exposing complex microbial communities (e.g. more than 10–100 different species, including unidentified ones) to environmental conditions, instead of grow axenic cultures in nature [38, 39] or co-cultivate two species under laboratory settings [59–64]. This could be a kind of a “black-box” approach with “traceable” and reproducible complexity, in which microbial cross-talk as well as unknown and/or non-standard inputs putatively act in concert to broadly activate microbial secondary metabolism. The platform necessary to achieve this goal seems to be currently missing and needs to be developed and implemented in a suitable laboratory device.
Microbes as threats, scientists as imaginary characters
Arguably, the general public gropes around in a different kind of darkness than that of microbiologists. As the relevance of (inter-species) microbial cross-talk in nature is still elusive to microbiologists, so seems the communication on the importance of microorganisms to be lagging, at least judging from the public perception of them. Microbes are widely associated with dirt and diseases even though, of all microorganisms, probably just a tiny fraction is pathogenic to humans, animals or plants.
These kind of misconceptions might be due to a general disaffection of society as a whole from scientific facts. Science is complicated and scientific results are occasionally exaggerated, oversimplified or misrepresented by media outlets or universities press-releases . But take a look at popular culture and you won’t find many positive characters representing a realistic scientist either. Subjectively, in the public eye scientists are often seen as either evil Drs. Frankenstein or nerds (without doubting that there might well be even evil nerds among scientists). By the words of comedian John Oliver, science is “the thing we love and respect so much we only allow scientists to be portrayed by the like of Arnold Schwarzenegger, Nicolas Cage and Al Pacino” . Neither is literature scoring better. According to the maxim “write what you know,” it could be a task for scientists to correct that. It is as if, aside from few exceptions , established scientists write exclusively memoirs or non-fiction. In line with this, according to the Royal Society in London the best science book ever written is not by a scientist but by the industrial chemist Primo Levi , beating among others Charles Darwin, Richard Dawkins and James Watson.
More than purely interesting
So why should scientists care, and in particular microbiologists? It would be too easy to bluntly put it as Richard Dawkins (who, quoting a journal editor, said “science is interesting and if you don’t agree you can fuck off”)  and we won’t. If, as Isaac Asimov believed, “the saddest aspect of life right now is that science gathers knowledge faster than society gathers wisdom,” scientists should feel concerned.
More understanding by the general public in the importance of microorganisms might lead to more acceptance and more public funding to microbial research. Informing the taxpayers on where their money goes and provide an understandable account of the outcomes should also be on the agenda of researchers. To facilitate this, in our opinion the scientific community might consider endeavours to close the gap between science and society as an activity advancing science; science outreaches could be considered as an additional valuable proxy to calculate the impact of researchers.
Misunderstanding about scientific facts can have serious consequences. Amongst the reasons for the increase in antibiotic resistance is the wrong use of these drugs by patients, who for example take them after a common cold or interrupt the treatment after first signs of healing and unnecessarily select for or favour the survival of resistant cells. Of course, several other factors are involved, like the (over-)use of antibiotics in intensive farming [84, 85]; similarly, pharmaceutical companies are less interested in the decade-long development of drugs that easily lose their effectivity [68–71]. Nonetheless, the distance between the general public and science is growing bigger, and ways to close this gap are sought after.
Science is entertaining, scientists are not nerds
The concept, invented and developed in Germany over the past 10 years , is now an integral part of science communication in the country, taking place in virtually every university town and regularly attracting a crowd of up to 1500 visitors. The format is spreading throughout other European countries as well as worldwide. The success of science slams is partly due to the fact that it provides the opportunity for direct communication between young scientists and the public. It allows researchers to break from the restraints of classic scientific communication, while the audience experiences their enthusiasm at the forefront of scientific discovery.
Many universities and scientific societies have embraced the science slam as a way to spread knowledge and connect with the public. During this year’s annual conference of the German Association of General and Applied Microbiology, for example, a specific “microbe slam” has been attended by over 1000 microbiologists . Science slams and several other science communication events, like for example the “Long Night of the Sciences” where institutions open their door to the general public, are cementing a collective conscience that science, like sports or the arts, is an integral part of our culture.
In need of more mixed cultures
Artists can substantially contribute to debates in scientific research. The so-called “microbial art” dates back to one of the founding fathers of microbiology, Alexander Fleming, who used petri dishes as canvas and pigmented cultures as “paint” . Almost a century onward, an increasing number of projects involving artists, curators and institutions have been developed under the common “art & science” label. However, artists working within this field are often pressured to fulfil the role of bridging the gap between the humanities and the sciences. Undeniably, C. P. Snow’s evaluation on the separation between the two cultures has been a recurring reference to emphasize the necessity of collaborative approaches between artists and scientists . We argue that such collaborative work can be achieved in more than one way and can be beneficial to everyone. Artists should feel encouraged to intervene in topical issues by questioning the ethical impacts on the society regarding the implementation of new technologies or by querying the collective understanding of scientific concepts and facts.
Artists should not simply act as translators of scientific ideas: they can shape them as well as the directions of the scientific research into areas that are more relevant and urgent for our society. With the words of the recently departed chemistry Nobel Prize laureate and graphic artist Harry Kroto: “In science, the universe is in control; in art, you are” . The perspective is in either case both scaring and fascinating, the outcomes—much in good science as in good art—unpredictable and enlightening.
A last word
It is essential that society engages in the debate on the importance of science in general, and in particular on those of microorganisms and their biotechnological potential. However, to counteract the antibiotic crisis, and to inform about the urgent necessity of this, is not an easy task. We believe that insights about communication among microorganisms—gained by microbiologists with appropriate new tools and approaches—as well as on microorganisms—by the concerted action of scientists, communicators, artists, scientific institutes and the general public—are acutely needed.
As the chemist, entrepreneur and pioneer in microbiology and immunology Louis Pasteur is often quoted with: “Messieurs, c’est les microbes qui auront le dernier mot!” (“Gentlemen, it’s the microbes who will have the last word!”). If we uncover microbial interactions and communication to the fullest, and talk more about microorganisms, there are good chances it is going to be a nice word.
CN conceived the idea and the structure of the manuscript, wrote it—except for the parts mentioned below—and edited the final version; BM wrote the parts discussing the interactions between science and the arts; JO those presenting science slams. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
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- Weaver SC, Costa F, Garcia-Blanco MA, Ko AI, Ribeiro GS, Saade G, et al. Zika virus: history, emergence, biology, and prospects for control. Antiviral Res. 2016;130:69–80.View ArticlePubMedGoogle Scholar
- Spengler JR, Ervin ED, Towner JS, Rollin PE, Nichol ST. Perspectives on West Africa Ebola virus disease outbreak, 2013–2016. Emerg Infect Dis. 2016;22:2013–6.View ArticleGoogle Scholar
- Callaway E. Devastating wheat fungus appears in Asia for first time. Nature. 2016;532:421–2.View ArticlePubMedGoogle Scholar
- Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Bull World Health Organ. 1929;2001(79):780–90.Google Scholar
- Salk JE, Krech U, Yougner JS, Bennett BL, Lewis LJ, Bazeley PL. Formaldehyde treatment and safety testing of experimental poliomyelitis vaccines. Am J Public Health. 1954;44:563–70.View ArticleGoogle Scholar
- Plotkin SA, Plotkin SL. The development of vaccines: how the past led to the future. Nat Rev Microbiol. 2011;9:889–93.View ArticlePubMedGoogle Scholar
- Wood JM, Robertson JS. From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza. Nat Rev Microbiol. 2004;2:842–7.View ArticlePubMedGoogle Scholar
- Demain AL, Sanchez S. Microbial drug discovery: 80 years of progress. J Antibiot. 2009;62:5–16.View ArticlePubMedGoogle Scholar
- Meyer V, Wu B, Ram AFJ. Aspergillus as a multi-purpose cell factory: current status and perspectives. Biotechnol Lett. 2011;33:469–76.View ArticlePubMedGoogle Scholar
- Richter L, Wanka F, Boecker S, Storm D, Kurt T, Vural Ö, et al. Engineering of Aspergillus niger for the production of secondary metabolites. Fungal Biol Biotechnol. 2014;1:4.View ArticleGoogle Scholar
- Pel HJ, de Winde JH, Archer DB, Dyer PS, Hofmann G, Schaap PJ, et al. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88. Nat Biotechnol. 2007;25:221–31.View ArticlePubMedGoogle Scholar
- Singleton P. Bacteria in biology, biotechnology and medicine. 6th ed. Chichester: Wiley; 2004.Google Scholar
- Sambrook J, Russell DW. Molecular cloning—Sambrook & Russel—vols. 1, 2, 3. Cold Spring Harbor, New York: CSH Press; 2001.Google Scholar
- Prenafeta-Boldú FX, Guivernau M, Gallastegui G, Viñas M, de Hoog GS, Elías A. Fungal/bacterial interactions during the biodegradation of TEX hydrocarbons (toluene, ethylbenzene and p-xylene) in gas biofilters operated under xerophilic conditions. FEMS Microbiol Ecol. 2012;80:722–34.View ArticlePubMedGoogle Scholar
- Shosuke Y, Kasumi H, Toshihiko T, Ikuo T, Hironao Y, Yasuhito M, et al. A bacterium that degrades and assimilatespoly(ethyleneterephthalate). Science. 2016;351:1196–9.View ArticleGoogle Scholar
- Goffeau A, Barrell BG, Bussey H, Davis RW, Dujon B, Feldmann H, et al. Life with 6000 genes. Science. 1995;274:563–7.Google Scholar
- Davis RH, Perkins DD. Timeline: Neurospora: a model of model microbes. Nat Rev Genet. 2002;3:397–403.View ArticlePubMedGoogle Scholar
- Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science. 2010;327:167–70.View ArticlePubMedGoogle Scholar
- Liang P, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell. 2015;6:363–72.View ArticlePubMedPubMed CentralGoogle Scholar
- Callaway E. Embryo editing gets green light. Nature. 2016;530:18–9.View ArticlePubMedGoogle Scholar
- Ledford H. CRISPR, the disruptor. Nature. 2015;522:20–4.View ArticlePubMedGoogle Scholar
- Sander JD, Joung JK. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. 2014;32:347–55.View ArticlePubMedPubMed CentralGoogle Scholar
- Rinke C, Schwientek P, Sczyrba A, Ivanova NN, Anderson IJ, Cheng J-F, et al. Insights into the phylogeny and coding potential of microbial dark matter. Nature. 2013;499:431–7.View ArticlePubMedGoogle Scholar
- Lok C. Mining the microbial dark matter. Nature. 2015;522:270–3.View ArticlePubMedGoogle Scholar
- Epstein SS. The phenomenon of microbial uncultivability. Curr Opin Microbiol. 2013;16:636–42.View ArticlePubMedGoogle Scholar
- Stewart EJ. Growing unculturable bacteria. J Bacteriol. 2012;194:4151–60.View ArticlePubMedPubMed CentralGoogle Scholar
- de Kruif Paul. Microbe hunters. New York: Harcourt, Brace and Co.; 1926.Google Scholar
- Bakken LR. Separation and purification of bacteria from soil. Appl Environ Microbiol. 1985;49:1482–7.PubMedPubMed CentralGoogle Scholar
- Stewart A, Brownbridge M, Hill RA, Jackson TA. Utilising soil microbes for biocontrol. In: Dixon GR, Tilston EL, editors. Soil microbiology and sustainable crop production. Heidelberg, Germany: Springer Science+Business Media; 2010; p. 315–71.Google Scholar
- Althani AA, Marei HE, Hamdi WS, Nasrallah GK, El Zowalaty ME, Al Khodor S, et al. Human microbiome and its association with health and diseases. J Cell Physiol. 2016;231:1688–94.View ArticlePubMedGoogle Scholar
- Luckey TD. Introduction to intestinal microecology. Am J Clin Nutr. 1972;25:1292–4.PubMedGoogle Scholar
- Abbott A. Scientists bust myth that our bodies have more bacteria than human cells. Nat. News. 2016. doi:10.1038/nature.2016.19136.Google Scholar
- Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014;20:16079–94.View ArticlePubMedPubMed CentralGoogle Scholar
- Mueller UG, Sachs JL. Engineering microbiomes to improve plant and animal health. Trends Microbiol. 2015;23:606–17.View ArticlePubMedGoogle Scholar
- Kyrpides NC, Eloe-Fadrosh EA, Ivanova NN. Microbiome data science: understanding our microbial planet. Trends Microbiol. 2016;24:425–7.View ArticlePubMedGoogle Scholar
- Byrd BAL, Segre JA. Infectious disease. Adapting Koch’s postulates. Science. 2016;351:224–6.Google Scholar
- Laukens D, Brinkman BM, Raes J, De Vos M, Vandenabeele P. Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design. FEMS Microbiol Rev. 2015;40:117–32.View ArticlePubMedPubMed CentralGoogle Scholar
- Nichols D, Cahoon N, Trakhtenberg EM, Pham L, Mehta A, Belanger A, et al. Use of ichip for high-throughput in situ cultivation of “uncultivable” microbial species. Appl Environ Microbiol. 2010;76:2445–50.View ArticlePubMedPubMed CentralGoogle Scholar
- Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, et al. A new antibiotic kills pathogens without detectable resistance. Nature. 2015;517:455–9.View ArticlePubMedGoogle Scholar
- Nguyen TLA, Vieira-Silva S, Liston A, Raes J. How informative is the mouse for human gut microbiota research? Dis Model Mech. 2015;8:1–16.View ArticlePubMedPubMed CentralGoogle Scholar
- Seiffert F, Bandow N, Kalbe U, Milke R, Gorbushina AA. Laboratory tools to quantify biogenic dissolution of rocks and minerals: a model rock biofilm growing in percolation columns. Front Earth Sci. 2016;4:1–10.View ArticleGoogle Scholar
- Goers L, Freemont P, Polizzi KM. Co-culture systems and technologies: taking synthetic biology to the next level. J R Soc Interface. 2014;11:20140065.View ArticlePubMedPubMed CentralGoogle Scholar
- Yang Y-L, Xu Y, Straight PD, Dorrestein PC. Translating metabolic exchange with imaging mass spectrometry. Nat Chem Biol. 2009;5:885–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Dev Biol. 2005;21:319–46.Google Scholar
- Mika F, Hengge R. Small regulatory RNAs in the control of motility and biofilm formation in E. coli and Salmonella. Int J Mol Sci 2013;14:4560–79.Google Scholar
- Hengge R. Principles of c-di-GMP signalling in bacteria. Nat Rev Microbiol. 2009;7:263–73.View ArticlePubMedGoogle Scholar
- Grube M, Cardinale M, Berg G. Bacteria and the lichen symbiosis. Fungal Assoc. 2012;77:363–72.Google Scholar
- Nash TH. Lichen biology. Cambridge: Cambridge University Press; 1996. p. 1–7.Google Scholar
- Bonfante P, Genre A. Mechanisms underlying beneficial plant–fungus interactions in mycorrhizal symbiosis. Nat Commun. 2010;1:48.View ArticlePubMedGoogle Scholar
- Taylor MW, Radax R, Steger D, Wagner M. Sponge-associated microorganisms: evolution, ecology, and biotechnological potential. Microbiol Mol Biol Rev. 2007;71:295–347.View ArticlePubMedPubMed CentralGoogle Scholar
- Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015;31:69–75.View ArticlePubMedPubMed CentralGoogle Scholar
- Sanchez JF, Somoza AD, Keller NP, Wang CCC, Rep NP. Advances in Aspergillus secondary metabolite research in the post-genomic era. Nat Prod Rep. 2012;29:351–71.View ArticlePubMedPubMed CentralGoogle Scholar
- Inglis DO, Binkley J, Skrzypek MS, Arnaud MB, Cerqueira GC, Shah P, et al. Comprehensive annotation of secondary metabolite biosynthetic genes and gene clusters of Aspergillus nidulans, A. fumigatus, A. niger and A. oryzae. BMC Microbiol. 2013;13:91.View ArticlePubMedPubMed CentralGoogle Scholar
- Lim FY, Sanchez JF, Wang CCC, Keller NP. Toward awakening cryptic secondary metabolite gene clusters in filamentous fungi. Methods Enzymol. 2012;517:303–24.View ArticlePubMedPubMed CentralGoogle Scholar
- Yu J-H, Keller N. Regulation of secondary metabolism in filamentous fungi. Annu Rev Phytopathol. 2005;43:437–58.View ArticlePubMedGoogle Scholar
- Shwab EK, Keller NP. Regulation of secondary metabolite production in filamentous ascomycetes. Mycol Res. 2008;112:225–30.View ArticlePubMedGoogle Scholar
- Ruiz B, Chávez A, Forero A, García-Huante Y, Romero A, Sánchez M, et al. Production of microbial secondary metabolites: regulation by the carbon source. Crit Rev Microbiol. 2010;36:146–67.View ArticlePubMedGoogle Scholar
- Bérdy J. Bioactive microbial metabolites. J Antibiot. 2005;58:1–26.View ArticlePubMedGoogle Scholar
- Wu C, Zacchetti B, Ram AFJ, van Wezel GP, Claessen D, Hae Choi Y. Expanding the chemical space for natural products by Aspergillus–Streptomyces co-cultivation and biotransformation. Sci Rep. 2015;5:10868.View ArticlePubMedPubMed CentralGoogle Scholar
- Schroeckh V, Scherlach K, Nützmann H-W, Shelest E, Schmidt-Heck W, Schuemann J, et al. Intimate bacterial–fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci USA. 2009;106:14558–63.View ArticlePubMedPubMed CentralGoogle Scholar
- König CC, Scherlach K, Schroeckh V, Horn F, Nietzsche S, Brakhage AA, et al. Bacterium induces cryptic meroterpenoid pathway in the pathogenic fungus Aspergillus fumigatus. ChemBioChem. 2013;14:938–42.View ArticlePubMedGoogle Scholar
- Onaka H, Mori Y, Igarashi Y, Furumai T. Mycolic acid-containing bacteria induce natural-product biosynthesis in Streptomyces species. Appl Environ Microbiol. 2011;77:400–6.View ArticlePubMedGoogle Scholar
- Ross C, Opel V, Scherlach K, Hertweck C. Biosynthesis of antifungal and antibacterial polyketides by Burkholderia gladioli in coculture with Rhizopus microsporus. Mycoses. 2014;57:48–55.View ArticlePubMedGoogle Scholar
- Benoit I, van den Esker MH, Patyshakuliyeva A, Mattern DJ, Blei F, Zhou M, et al. Bacillus subtilis attachment to Aspergillus niger hyphae results in mutually altered metabolism. Environ Microbiol. 2015;17:2099–113.View ArticlePubMedGoogle Scholar
- de Lima Procópio RE, da Silva IR, Martins MK, de Azevedo JL, de Araújo JM. Antibiotics produced by Streptomyces. Braz J Infect Dis. 2012;16:466–71.Google Scholar
- Liu G, Chater KF, Chandra G, Niu G, Tan H. Molecular regulation of antibiotic biosynthesis in Streptomyces. Microbiol Mol Biol Rev. 2013;77:112–43.View ArticlePubMedPubMed CentralGoogle Scholar
- Svahn KS, Chryssanthou E, Olsen B, Bohlin L, Göransson U. Penicillium nalgiovense Laxa isolated from Antarctica is a new source of the antifungal metabolite amphotericin B. Fungal Biol Biotechnol. 2015;2:1.View ArticleGoogle Scholar
- Brown GD, Denning DW, Levitz SM. Tackling human fungal infections. Science. 2012;336:647.View ArticlePubMedGoogle Scholar
- Denning DW, Bromley MJ. How to bolster the antifungal pipeline. Science. 2015;347:1414–6.View ArticlePubMedGoogle Scholar
- Perros BM. A sustainable model for antibiotics—How can we foster the development of novel drugs against resistant bacteria? Science. 2015;347:1062–4.View ArticlePubMedGoogle Scholar
- Baker BS. A return to the pre-antimicrobial era? Science. 2015;347:1064–6.Google Scholar
- Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov. 2007;6:29–40.View ArticlePubMedGoogle Scholar
- Büttel Z, Díaz R, Dirnberger B, Flak M, Grijseels S, Kwon MJ, et al. Unlocking the potential of fungi: the QuantFung project. Fungal Biol Biotechnol. 2015;2:6.View ArticleGoogle Scholar
- Meyer V, Nevoigt E, Wiemann P. The art of design. Fungal Genet Biol. 2016;89:1–2.View ArticlePubMedGoogle Scholar
- Meyer V. Genetic engineering of filamentous fungi—progress, obstacles and future trends. Biotechnol Adv. 2008;26:177–85.View ArticlePubMedGoogle Scholar
- Meyer V, Fiedler M, Nitsche B, King R. The cell factory Aspergillus enters the big data era: opportunities and challenges for optimising product formation. Adv Biochem Eng Biotechnol. 2015;149:91–132.PubMedGoogle Scholar
- Scazzocchio C. Fungal biology in the post-genomic era. Fungal Biol Biotechnol. 2014;1:7.View ArticleGoogle Scholar
- Cairns TC, Studholme DJ, Talbot NJ, Haynes K. New and improved techniques for the study of pathogenic fungi. Trends Microbiol. 2016;24:35–50.View ArticlePubMedGoogle Scholar
- Madigan MT, Martinko JM, Bender KS, Buckley DH, Stahl DA. Brock biology of microorganisms. 14th ed. Boston: Benjamin Cummings; 2014.Google Scholar
- https://www.youtube.com/watch?v=0Rnq1NpHdmw. Accessed 16 June 2016.
- http://www.djerassi.com/. Accessed 16 June 2016.
- https://www.theguardian.com/science/2006/oct/21/uk.books. Accessed 16 June 2016.
- https://www.youtube.com/watch?v=ysxG5jFeTME. Accessed 16 June 2016.
- Jean-Claude P. Antibiotic resistance: the emergence of plasmid-mediated colistin resistance enhances the need of a proactive one-health approach. FEMS Microbiol Lett. 2016;363:1–2.View ArticleGoogle Scholar
- Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16:161–8.View ArticlePubMedGoogle Scholar
- http://www.scienceslam-darmstadt.de/. Accessed 16 June 2016.
- https://microbeslam.wordpress.com/. Accessed 16 June 2016.
- http://www.microbialart.com/galleries/fleming/. Accessed 16 June 2016.
- Snow CP. The two cultures. New York: Cambridge University Press; 1998.Google Scholar
- http://www.mayayoghurt.net (Maya Yoghurt, artist website of Maja Smrekar). Accessed 16 June 2016.
- https://2016.transmediale.de/content/1000-handshakes (1000 Handshakes, website of Transmediale 2016). Accessed 16 June 2016.
- Magrini B. Hackteria: an example of neomodern activism. In: Aceti L, Jaschko S, Stallabrass J, Balaskas B, editors. Red art: new utopias in data capitalism, Vol. 20. Leonardo Electronic Almanac. San Francisco: Leonardo/ISAST; 2014. p. 58–71.Google Scholar
- http://www.daisyginsberg.com/work/designing-for-the-sixth-extinction. Accessed 16 June 2016.
- https://twitter.com/laurasprechmann/status/662165383470710784. Accessed 16 June 2016.