“Microbes in Space: Outer Space and Killer Bacteria” by Elisabeth Wachter

Microbes in Space: Outer Space and Killer Bacteria

Elisabeth Wachter, Frederick Community College

Abstract

In a study by Wilson et al., researchers noted that a sample of Salmonella that had spent time in space had a noticeably increased virulence and mortality rate when used to infect mice back on Earth. After preliminary research, it was noted that the host factor for bacteriophage Qβ (Hfq) and the altered fluid dynamics of microgravity play a pivotal role in the altered cell function observed by Wilson et al. Through a review of the literature, this research project sought to explain the mechanisms and functions of Hfq and how the fluid dynamics in microgravity alter the function of Hfq and cause increased virulence. With support from existing research, I suggest that Hfq could be the target of treatments to reduce biofilm formation, making it more difficult for bacteria to survive antibiotics, and as a target to alter the function of proteins that contribute to the invasive capabilities of bacteria. Future research can focus on cultivating these innovative ideas through the experimental research environment to determine their viability as a way to protect astronauts’ health during long-term space travel. 

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Wilson et al.’s 2006 study

In 2006, a research study conducted on space shuttle Atlantis made a startling discovery. When a strain of Salmonella grown on the International Space Station (ISS) was brought back to Earth and used to infect mice, it had a significantly higher infection rate and lethality among the experimental mouse population than the control group that was infected with Salmonella cultured on Earth. The salmonella grown on the ISS started showing mortalities in the mice at a dosage of 10⁵ colony forming units as opposed to the appearance of mortalities at 10⁷ colony forming units for the Earth samples, demonstrating that the spaceflight salmonella needed 2 million less bacteria to create a viable colony (Fig. 1a). While the lowest survival rate 25 days after infection for the Earth cultures was 40%, the spaceflight samples had a 10% survival rate after the same amount of time elapsed (Fig. 1b). Additionally, the Salmonella cultures on Earth had a much higher LD₅₀ value (a measure of the dosage of a specific compound necessary to result in death of half the population) of 13 million cells, while the spaceflight group had an LD₅₀ of less than half that (5 million). The spaceflight Salmonella additionally demonstrated an increased ability to survive in the presence of macrophage immune cells. The study’s results also noted that the regulator protein Hfq, a host factor for bacteriophage Qβ, experienced a .298 fold-change (or almost a 30% decrease in genetic expression). These findings show that spaceflight conditions activated mechanisms that made the bacteria more virulent and indicate a link between Hfq and the increased virulence. Additionally, the study noted an aggregation of the spaceflight cells in the extracellular mix, indicative of biofilm formation, which the Earth cultures did not have (Wilson et al., 2007). 

Figure 1a: mortality rates of ground control group of mice (grey) vs. experimental spaceflight group (purple) at different dosages throughout the duration of Wilson et al.’s study (Wilson et al., 2007).

Figure 1b: survival rates between control group of mice (grey squares) and spaceflight experimental group (black diamonds) over the 25 days of Wilson et al.’s study (Wilson et al., 2007). 

Hfq function

Hfq is a regulatory protein with a hexameric ring structure found in prokaryotic cells (Wilson et al., 2007; Cech et al., 2016). Wilson et al. note Hfq’s status as a highly conserved protein across multiple different species, indicating that it has a critical role for cellular survival and thus has been selected for by evolution repeatedly (Wilson et al., 2007). Hfq influences a wide array of cellular functions, including growth rate, UV and osmo-sensitivity, and biofilm formation through its interactions with small regulatory RNAs (or sRNAs) (Malabirade et al., 2018b). Hfq is also responsible for the cellular stress response and regulates a variety of virulence factors, including negatively regulating biofilm formation. Hfq also regulates the tra operon, a series of genes that encode the F plasmid transfer apparatus, which facilitates lateral gene transfer and is a major mechanism bacteria use to form antibiotic resistance (Wilson et al., 2007; McLean, 2025). Hfq influences cellular growth rate by influencing plasmid supercoiling through its interactions with sRNAs, and studies have noted that when expression of Hfq is interrupted, supercoiling increases. Plasmid supercoiling can increase replication efficiency during reproduction (Sahoo & Bardwell, 2025; McLean, 2025). Additionally, Hfq more directly influences the virulence of bacteria through its regulation of the sipC cell invasion protein, a protein that assists bacteria in the infection of cells and was noted to be upregulated in Wilson et al.’s Salmonella experiment (Wilson et al., 2007; Vogel & Luisi, 2011). In L. monocytogenes, Hfq plays a role in resisting osmotic and ethanol stress due to its role in biofilm formation; when expression of hfq is reduced, biofilm formation increases (Wilson et al., 2007). This explains the observed cellular aggregation in Wilson et al.’s study. Through the creation of an extracellular mix, biofilm protects bacteria from environmental threats, including antibiotic and host immune responses (Bloch et al., 2025; Abebe, 2020). In space, hfq’s decreased expression allows biofilm formation to protect cells from environmental stressors, and this confirms previous observations that noted the consistent occurrence of biofilm formation in microgravity samples and directly relates to Hfq’s role in virulence (Malabirade et al., 2018b). Expression of hfq is decreased in response to the stressful conditions of space to help bacteria survive the altered conditions of microgravity through the previously described functions and mechanisms regulated by Hfq (Milojevic & Weckwerth, 2020).

Factors that could contribute to the increased virulence of bacteria in space

There are multiple potential stressors introduced by the spaceflight environment that affect bacterial behavior. Perhaps most notable are the cosmic, radiation, UV, and other electromagnetic (EM) waves present in space. However, decreased expression of hfq has been noted in low-shear modeled microgravity (LSMMG) experiments on Earth that simulated microgravity using a rotating wall vessel but did not expose bacteria to EM waves, indicating that they are not the main cause of increased virulence (Wilson et al., 2007). Another environmental stressor for bacteria in space is the altered fluid dynamics of space (and the resulting oxidative strain) (Li et al., 2024). 

Altered fluid dynamics of space

Due to their small size, microgravity should not have a significant effect on bacterial cellular functions. However, research has noted the significant effects of microgravity on bacterial cells (Wilson et al., 2007; Li et al., 2024). In space, the major stressors are heat, desiccation, UV, and oxidative stress, which could all potentially lead to an increased expression of hfq (Bloch et al., 2025; Li et al., 2024). One origin of oxidative stress in space is how fluid motion functions in microgravity. Specifically, the only way for microbes to move substances in and out of cells is by relying on passive diffusion (driven by Brownian motion) due to the lack of gravity-driven fluid motion (namely convection, buoyancy, and sedimentation). Buoyancy is the effect created when objects displace a liquid while they experience the pull of gravity. This means that denser objects will move more quickly through liquids when gravity pulls on them, as they can displace liquids more easily. The movement through fluid and the resultant displacement creates density-driven convection, which moves and mixes substances in the suspending fluid. However, in space, due to a lack of gravity, this mechanism does not function the same, and substances do not separate based on density. This makes it harder for cells to obtain fresh nutrients and move waste products away from themselves, increasing oxidative stress on the bacterium (Sharma & Curtis, 2022; Li et al., 2024). Li et al. show that this mechanism also causes growth factors to accumulate more readily outside cells, creating an autocrine signal that causes cells to start dividing earlier (causing a shorter lag phase) and to experience a notably longer exponential growth phase than usual (Li et al., 2024). This correlates with previous hypotheses that theorized altered cell function could be caused by the altered extracellular mix of cells. Hfq has been shown in previous research to be reduced when bacteria experience stressful environments to increase their survival (Sharma & Curtis, 2022; Bourzac, 2007; Milojevic & Weckwerth, 2020). 

Figure 2: fluid dynamics in a normal 1g environment (left), which allows products to cycle in the extracellular matrix vs. in the microgravity of spaceflight (right), where products accumulate around cells changing extracellular concentrations (Li et al., 2024).

Cause of increased virulence of bacteria in space

In Wilson et al.’s study, decreased expression of Hfq increased the virulence of S. typhimurium through two major mechanisms. First, the altered fluid dynamics of space increased the growth rate of Salmonella; a faster proliferation rate would make it harder for the mice's immune systems to destroy bacterial infections. Additionally, Hfq acts as a negative regulator for the tra operon that encodes the F plasmid apparatus (which allows bacteria to exchange genetic adaptations with each other) (Wilson et al., 2007). When a cell gains a genetic adaptation, for example, antibiotic resistance, it creates a small plasmid that contains the adaptation gene. Even though bacteria reproduce asexually, they can share these adaptations with each other through lateral gene transfer. When the bacterium with the adaptation plasmid comes near another bacterium that does not, it extends a pilus to anchor to another cell and widens the initial connection into a mating bridge, a passageway between the two bacteria. The cell then shares a copy of its plasmid, resulting in both cells having the antibiotic resistance gene. In this way, whole colonies of bacteria can gain antibiotic resistance (Hillis et al., 2014). Thus, when Hfq’s expression is reduced in space, bacteria can adapt to their environment and develop antibiotic resistance more efficiently and effectively. As this mechanism is negatively regulated by Hfq’s influence on the tra operon, reduced expression of hfq in space could lead to increased antibiotic resistance in microgravity through upregulated lateral gene transfer (Wilson et al., 2007; Virolle, 2020). Research by Horneck et al. seems to confirm this hypothesis, as their study notes that microbes in space can proliferate and survive in concentrations of antibiotics that are normally inhibitory (Horneck et al., 2010). 

Figure 3: Bacterial lateral gene transfer. In 1, cell A has a plasmid with an adaptation (in green) while cell B does not. In 2, the cells utilize a pilus to form a connection, that in 3, widens into a mating or conjugating bridge. Cell A duplicates its plasmid adaptation and sends a copy across the conjugating bridge to cell B. in 4, the cells separate and both now have the adaptation (drawn by E. Wachter from a description of lateral gene transfer from Hillis et al., 2014).

Implications of increased virulence of bacteria in space

The increased virulence and antibiotic resistance of bacteria in microgravity raises concerns for the health of astronauts on long-term space travel (for example, a mission to Mars) where there would be ample opportunity for bacteria to mutate. A specific danger bacteria in microgravity can pose to crews in space, bacteria in biofilm colonies have been noted to contaminate water supplies on the International Space Station (ISS). The presence of biofilm gives bacterial colonies a mechanism to survive antimicrobial treatments in the water processing systems of the ISS (lowering the effectiveness of sanitary procedures for potable water). Coupled with the increased evolution of antimicrobial resistance through upregulated lateral gene transfer, bacteria in water supplies can evolve to gain antibiotic resistance and utilize biofilms as a mechanism to survive standard antimicrobial treatments. The crew of the ISS was forced to change the antibacterial chemicals they were using to sanitize their water to solve the problem. However, this highlights how crews in space are highly susceptible to bacterial infections from water supplies and water processing, especially on long-term missions where astronauts have a limited availability of different antimicrobial agents and cannot change chemicals every time bacteria gain antibiotic resistance to a specific chemical to prevent bacterial colonies from growing in water processing systems. Additionally, studies have noted that biofilm has a corrosive effect on the types of metals used to construct spacecraft. Coupled with the increased antibiotic resistance of bacteria in space, these findings raise major concerns for the safety of astronauts on long-term missions (McLean, 2025). 

Potential Solutions

However, a solution could lie in the problem. Utilizing Hfq as a target for treatment or prevention could prove to be a successful solution to the increased risk of infection and material corrosion during space travel. Multiple researchers suggest targeting post-transcriptional regulators like Hfq in the development of antimicrobial treatments (Wilson et al., 2007; Roncarati et al., 2022; Milojevic & Weckwerth, 2020). Roncarati et al. (2022) propose taking advantage of Hfq’s role as a posttranscriptional regulator to alter the function of virulence factors (for example, biofilm formation and invasion proteins) to reduce the invasive capabilities of microbes and make bacteria more susceptible to traditional antibiotics (Roncarati et al., 2022; Kasthuri et al., 2023). A treatment that targets Hfq could inhibit bacteria’s ability to perform lateral gene transfer, which would prevent bacterial colonies from sharing antibiotic resistance genes with each other. Treatments that prevent bacteria from forming biofilms could potentially make bacteria that have antibiotic resistance through biofilm mechanisms susceptible to traditional antibiotic therapies. Antimicrobial treatments that target Hfq could have applications in the medical field as well as in space to disinfect surfaces and to prevent the metallic corrosion caused by biofilms. Research to investigate the viability of these applications for Hfq as a drug target is already underway. For example, through its C-terminal region, Hfq can assemble amyloid protein structures, which is how it is able to promote biofilm formation in bacteria. As biofilms are one of the major mechanisms bacteria utilize to adapt to antibiotics and render their functions useless (by physically blocking the antibiotic agent from interacting with the bacterial cell), the C-terminal makes sense as a target to prevent bacteria from being able to develop antibiotic resistance (Turbant et al., 2021). Turbant et al. (2021) investigated this function of Hfq and note that the medication apomorphine can be used as an antibacterial agent to block bacterial antibiotic adaptability through its targeting of the Hfq amyloid region. 

Summary

In summary, research has indicated that when bacteria spend time in space, they become more virulent (Wilson et al., 2007). Research that utilizes simulations of microgravity on Earth in a lab environment has shown that the observed increase in virulence was largely due to the altered function of fluid dynamics in space and not the effects of radiation as previously hypothesized (Li et al., 2024). Li et al. (2024) explained that through the altered fluid dynamics of space, expression of hfq is downregulated, allowing cells to exchange genetic adaptations, reproduce more easily, and to more easily infect host cells through the decreased regulation of invasion proteins (Wilson et al., 2007). These mechanisms allow microbe populations to grow larger and more rapidly, making it easier for bacteria to overwhelm host immune responses and the upregulation of sipC makes it easier for bacteria to invade host cells. Additionally, due to the increased biofilm and heightened operation of the tra operon in microgravity, bacteria can more readily develop antibiotic resistance, raising concerns for human spaceflight and the potential for an increased evolution of bacteria into superbugs during long-term space missions. Coupled with increased virulence and the corrosive effect of biofilms in space, the altered behavior of bacteria in microgravity raises concerns for the safety of crews on long-duration space exploration missions. However, targeting Hfq for treatment options and virulence prevention could be not only a solution to protect crews in space but also a method to kill superbugs that have become resistant to antibiotics on Earth, as hypothesized by Wilson et al., Roncarati et al., Kasthuri et al., and experimentally verified by Turant et al. using the drug apomorphine. Future research into this subject could not only protect future astronauts in space, but it could also save lives here on Earth today.

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