From Superbugs to Solutions: Microgravity, Antibiotic Resistance, and Biomanufacturing

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Genetically modified microorganisms have massive implications for agriculture, chemistry, and medicine. 

Yet the large-scale manufacturing of industrial enzymes, therapeutic proteins, antibiotics, and other critical products can be hampered by terrestrial challenges.

Microgravity environments are being eyed as prime real estate for the production of vital commodities and novel products across a spectrum of sectors.

‍Litegrav addresses traditional challenges to microgravity research, such as cost, logistical challenges, and reproducibility, with simulated solutions. 

‍Simulated microgravity reduces gravitational force and fluid shear while preventing sedimentation to ensure an even distribution of nutrients and waste for microbial research, which profoundly impacts cellular processes (Klaus, 1998).

In microgravity, microorganisms (like E. coli) reproduce more rapidly, growing faster with shortened lag phases; they also multiply faster during the exponential (log) phase, attaining a larger final cell count during the stationary phase (Kim, 2014).

In microgravity, bacteria become more resistant to antibiotics. This is thought to be due in part to the absence of sedimentation and fluid motion, causing substances around the cells to move less (Brown, 2002).

The effects induced by microgravity could be useful for improving biomanufacturing and reducing costs. Bacteria in microgravity form stronger protective layers, which make them harder to kill with antibiotics. 

Microgravity can facilitate antibiotic research by making useful secondary metabolites, including antibiotic compounds.

The novel conditions, real or simulated, can help us make more antibiotics; they can also assist in the quest for new protocols and therapeutics for combating superbugs (Searles, 2011).

And when it comes to secondary metabolites, microgravity can give extraordinary results, whether it is an antibiotic or an antitumorigenic. While they are not essential for the growth and development of the microorganisms that make them, they might be critical to the health of plants, animals, and humans (Ruiz, 2010).

Microgravity can increase the production of certain compounds in microbes. Streptomyces plicatus made more of the antibiotic actinomycin D in space, while Bacillus brevis furnished more gramicidins when grown in a special Rotating Wall Vessel microgravity bioreactor compared to a shaking flask. 

In the study of Fang et. al. glucose interference in the production of microcin B17 by E. coli dropped sevenfold, compared to the 100 fold interference in normal gravity conditions. This is significant, as glucose slashes secondary metabolites like microcin B17. It is also a major driver of E. Coli’s primary metabolism (Fang, 2000, Demain, 2001).

A simulated microgravity environment supported by diamagnetic levitation led to more secondary metabolites from Streptomyces avermitilis. Researchers tested different simulated gravity levels (0g, 1g, and 2g) in a strong magnetic field, studying how S. avermitilis grows and makes the avermectin. More avermectin was made in microgravity, a compound that has profound antiparasitic effects in humans and animals (Liu, 2011).

In simulated microgravity conditions, E. coli shifted its production of microcin B17 from inside the cells to the surrounding fluid. The shift was not attributed to the gravity level, but rather to the low shear stress bioreactor conditions. 

In fact, increasing the shear with even a single glass bead caused Microcin B17 to remain inside the cells (Fang, 1997). In other words, for a variety of reasons microgravity may also reduce the production of certain compounds. 

Favorable and unfavorable results let researchers study potential benefits and drawbacks to better prepare us to handle the eventualities we will face on Earth and astronauts must prepare for in space. 

‍Litegrav is committed to providing microbiologists with the tools they need to stop the next superbug in its tracks or facilitate the biomanufacturing of vital secondary metabolites to bring necessary antibiotic, antiparasitic, and antiviral therapeutics to those who need them. 

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References and Works Cited

Brown RB, Klaus D, Todd P. Effects of space flight, clinorotation, and centrifugation on the substrate utilization efficiency of E. coli. Microgravity Sci Technol. 2002;13(4):24-9. doi: 10.1007/BF02881678. PMID: 12521048.

Demain AL, Fang A. Secondary metabolism in simulated microgravity. Chem Rec. 2001;1(4):333-46. doi: 10.1002/tcr.1018. PMID: 11893073.

Fang A, Pierson DL, Koenig DW, Mishra SK, Demain AL. Effect of simulated microgravity and shear stress on microcin B17 production by Escherichia coli and on its excretion into the medium. Appl Environ Microbiol. 1997 Oct;63(10):4090-2. doi: 10.1128/aem.63.10.4090-4092.1997. PMID: 9327574; PMCID: PMC168721.

Fang A, Pierson DL, Mishra SK, Demain AL. Relief from glucose interference in microcin B17 biosynthesis by growth in a rotating-wall bioreactor. Lett Appl Microbiol. 2000 Jul;31(1):39-41. PMID: 10886612.

Kim HW, Matin A, Rhee MS. Microgravity alters the physiological characteristics of Escherichia coli O157:H7 ATCC 35150, ATCC 43889, and ATCC 43895 under different nutrient conditions. Appl Environ Microbiol. 2014 Apr;80(7):2270-8. doi: 10.1128/AEM.04037-13. Epub 2014 Jan 31. PMID: 24487539; PMCID: PMC3993155.

Klaus DM. Microgravity and its implication for fermentation biotechnology. Trends Biotechnol. 1998 Sep;16(9):369-73. doi: 10.1016/s0167-7799(98)01197-4. PMID: 9776612.

Liu M, Gao H, Shang P, Zhou X, Ashforth E, Zhuo Y, Chen D, Ren B, Liu Z, Zhang L. Magnetic field is the dominant factor to induce the response of Streptomyces avermitilis in altered gravity simulated by diamagnetic levitation. PLoS One. 

2011;6(10):e24697. doi: 10.1371/journal.pone.0024697. Epub 2011 Oct 19. PMID: 22039402; PMCID: PMC3198441.

Ruiz, B., Chávez, A., Forero, A., García-Huante, Y., Romero, A., Sánchez, M., et al. (2010) Production of microbial secondary metabolites: regulation by the carbon source. Crit. Rev. Microbiol. 36, 146–167. doi: 10.3109/10408410903489576.

Searles SC, Woolley CM, Petersen RA, Hyman LE, Nielsen-Preiss SM. Modeled microgravity increases filamentation, biofilm formation, phenotypic switching, and antimicrobial resistance in Candida albicans. Astrobiology. 2011 Oct;11(8):825-36. doi: 10.1089/ast.2011.0664. Epub 2011 Sep 21. PMID: 21936634.

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