Stuck on You: How Bacteria Migrate and Adhere to Their Hosts
Imagine you’re a bacterial cell living on the skin of a human. It’s not an easy life, with the constant sweating and sloughing and rubbing that threaten to dislodge you from your home. Your friends in the gut don’t have it much easier—all that food passing through, not to mention the fierce competition. Microbial relatives clinging to the leaves of plants or pebbles in the soil face similar pressures that make the act of staying put something of an accomplishment. You quickly realize that to be a bacterium is to hold on for dear life—until, of course, it’s time to let go.
Host Colonization and Adherence Go Hand in Hand
Scientists have long been interested in how microbes adhere to the surfaces and beings of the world. This interest stems, in part, from the understanding that colonization is intricately linked to bacterial adhesion. One cannot colonize if one cannot stay.
Over the years, researchers have identified a throng of mechanisms that stick bacteria to hard (and not-so-hard) places. A classic example: pili. These hair-like appendages—of which the ubiquitous type IV variety is a key representative—bind specific receptors on host cell surfaces. Other protrusions like flagella modulate adhesion, too, as do tacky sugar matrices (e.g., the holdfast in Caulobacter crescentus) or extracellular polymeric substances that attach bacteria to surfaces and each other.
While the mechanics of these and other adhesive tools are relatively well-defined, how they are deployed across the vast microbial world is less clear. This is especially true in the context of complex communities like the gut microbiome, where a large fraction of microbial physiology is unknown.
“I think that, from the perspective of the microbiome, we don't really understand a lot about how beneficial or commensal bacteria can colonize the animal gut,” said Robert Luallen, Ph.D., an associate professor of biology at San Diego State University. His lab studies the natural microbiota of Caenorhabditis elegans, a nematode whose transparent body, quick generation time and microbiome assembly/dynamics make it a prime model organism for exploring host-microbe interactions.
Recently, the Luallen Lab and their collaborators identified several bacteria clinging to the guts of C. elegans collected from the wild. When researchers prompted 2 of the newly identified strains belonging to the Enterobacterales order to compete against each other (i.e., they colonized nematode larva lacking a microbiome with both Enterobacterales strains at the same time), the bacteria “sort of carved out a niche,” Luallen said. “One of them seemed to prefer the anterior end [of the gut], and then the other one just colonized everything else after the anterior end. It was really quite fascinating.”
The details of how and why the strains attach to the gut in the orientation they do are still under investigation. But subsequent experiments have shown that several isolates of one of the species (Lelliottia jeotgali) harbor large, natural plasmids in their genomes. Notably, the team determined that the plasmids encode type IV pili; knocking out pili gene expression reduces the bacteria’s ability to attach by 50-60%. Other environmental isolates of the same species do not have the plasmids and do not attach to C. elegans.
The presence of type IV pili is not surprising in and of itself, given how widely expressed they are. But the idea that commensal bacteria can potentially exchange adherence factors for host colonization via transmissible plasmids is a fairly new concept.
“The research that we're doing is finding these core paradigms that may or may not be conserved across organisms,” Luallen said. “And so, maybe the core paradigm that a microbe must evolve with its host is not necessarily true. Maybe you need DNA segments that evolve with the host, and then bacteria can just transmit that DNA back and forth from each other. I doubt it's true for all the microbiome, but it might be true for some of it.”
Stuck on You Like Super Glue
One thing that is true for microbes far and wide is that adherence is tricky. Whether bacteria are colonizing a rock in a stream or somebody’s gut, factors like surface charge, hydrophobicity, the presence of necessary receptors and shear force dictate success. The latter is especially important, as biological systems are rife with flows and forces that can dislodge tiny life.
And yet, bacteria persist. Many have evolved ways to latch onto surfaces with an iron grip. Some interactions, known as catch bonds, become stronger under mechanical stress. In these cases, force causes structural changes in interacting molecules on the bacteria and/or the host to fortify the hold. For example, catch bonds between the FimH adhesin protein on uropathogenic Escherichia coli and mannose on host bladder cells allow the bacterium to resist shear forces during urination, leading to urinary tract infections. Staphylococcus aureus also leverages catch bonds to stick to skin.
In fact, when it comes to strong bacterial binders, Staphylococcus spp. are near the top of the list. Andrew Herr, Ph.D., a professor at Cincinnati Children’s Hospital Medical Center, studies adherence mechanisms of the skin-colonizing species S. epidermidis (a commensal) and S. aureus (a bacterium that contributes to diseases like atopic dermatitis). His lab is interested in 2 large cell wall-associated proteins: accumulation associated protein (Aap) in S. epidermidis and its ortholog SasG in S. aureus. They’ve specifically homed in on the proteins’ lectin domains—regions that bind glycans on host cell surfaces.
“The lectin domains from Aap and SasG mediate adhesion to healthy corneocytes. This can be distinct from what you see, for example, in atopic dermatitis, because the skin in that case is damaged,” revealing different ligands and receptors, explained Herr, who will be presenting at the Mechanism Discovery Meeting at ASM Microbe 2026. “So, there are different sets of adhesions that recognize different corneocyte proteins. But in the case of healthy skin, it's Aap and SasG that are important.”
Using single-cell force spectroscopy—a method in which a bacterium expressing proteins of interest is attached to a probe, touched down onto a host cell and pulled back up again to measure its adhesiveness—Herr and his collaborators have shown that Aap and SasG are especially grabby. “Aap and SasG have a surprisingly strong adhesive force … at least an order of magnitude stronger than you normally would see for a lectin binding to a glycan,” he said, likely due to protein-protein interactions with the receptor mediated by structural features at the distal end of the lectin domain. For context, the force that binds Aap and SasG to corneocytes is roughly 10-100x that required to unfold a protein.
While the identities of the corneocyte receptors of Aap and SasG are still unknown, researchers have discovered other Staphylococcal adhesins with similarly powerful grips in the context of both healthy and diseased skin. Herr highlighted that zooming in on these molecular interactions paves the way for therapeutic applications, such as topical creams containing small molecular inhibitors that prevent S. aureus colonization but leave S. epidermidis unharmed.
Keep Your Friends Close
But the story is bigger than extreme host binding. Bacteria don’t just stick to surfaces; they also stick to each other, which, in turn, helps them stick to surfaces. In a way, biofilm formation is an adhesive mechanism in and of itself. How bacteria form these hardy cellular conglomerations is as integral to the adhesion conversation as direct bacteria-surface interactions.
Herr’s work covers both sides of the discussion. “What’s fascinating to me is that ... in many species, you'll have entire multi-protein organelles, like pili and fimbriae, that mediate either host adhesion or biofilm formation. And yet, [with Aap and SasG], you have a single protein that can accomplish all those functions,” he said.
The lectin domains of Aap and SasG can be enzymatically processed and removed, which promotes biofilm formation. Herr’s team found that what’s left of the proteins on the bacterial cell surface—long strings of amino acids—extend out as long filaments. In the presence of zinc (a trace element found in the skin), filaments from neighboring Staphylococcus cells interact to form twisted ropes, holding the cells together and anchoring them into place. Combine that mechanism with their ultrastrong attachment to host tissues and it is little wonder Staphylococcus bacteria are adhesion superstars.
They are not alone, though. Biofilms are the bread and butter of the bacterial world; there are countless molecular interactions that dictate their formation on everything from microplastics to catheters to the surface of teeth. For instance, the dental plaque-associated bacterium Veillonella parvula uses a set of large adhesins to co-aggregate with other plaque bacteria (namely Streptococcus oralis, S. gondii and Actinomyces oris). Co-aggregation reduces the distance between disparate bacterial species. When these species get together, they can metabolically support one another. Indeed, V. parvula relies on streptococci to supply the lactate needed for its growth.
In the mouth, on the skin and across the board, bacteria are stronger (and stickier) together.
The Mechanics of Moving On
It’s clear the forces and flows of a microbe’s environment, combined with interactions with its brethren, help lock it down. But here’s the thing: bacteria move. There comes a point when, individually or collectively, passively or actively, bacteria migrate from one place to another. Some of the same environmental and physiological factors that determine whether bacteria stay also influence why and how they go. But what exactly is responsible for the transition from sitting still to moving along?
“My big picture goal is to try and make sense of how cells make decisions about their behavior,” said Navish Wadhwa, Ph.D., an assistant professor in the Department of Physics at Arizona State University. “This is a common theme among lots of microbiologists, but I think what distinguishes my lab is the approach that we take to study this, where we really emphasize interactions [with] physical forces [and] surrounding fluid or surfaces.”
In collaboration with David Blair, Ph.D., at the University of Utah, Wadhwa’s team uncovered a new way in which bacteria migrate across surfaces. The mechanism, called swashing, has been observed in vitro with Salmonella and E. coli and does not rely on active propulsion by flagella or other appendages that drive some forms of motility. Rather, fermentation by-products produced at the colony edge, including acetate and formate, draw water out of the agar, creating a bulge of fluid. Bacteria are lifted and surf the fluid wave outward. The phenomenon is akin to waves on a beach pushing debris onto the shore.
Swashing has only been observed on agar plates. But Wadhwa thinks that “given the right set of conditions, this kind of interplay between the physics and the biology of the cell could drive expansion through similar mechanisms,” including potentially in vivo. In any case, the work “brings into question everything that we understand about bacterial surface motility,” he said. “Because I think the paradigm really has been that flagella are essential for expanding on top of surfaces, and we are seeing more examples in which that is not the case.”
The idea that metabolism shapes environmental conditions to facilitate migration has been observed in other contexts, too, including those that directly involve adhesion factors. A recent pre-print (which, as of this writing, has not been peer-reviewed) showed that the human pathogen Neisseria gonorrhoeae strongly expresses type IV pili and exhibits tight cell–cell binding during early colony formation. As colonies mature, respiration lowers oxygen levels in the colony center, reducing type IV pili expression and weakening cohesion among cells. This looser structure enables colony eversion, allowing live and dead central cells to flow outward—a process that clears nonviable members and aids dispersal of live cells.
As such, adhesion, both to a surface and/or to other cells, may “make sense” until metabolic processes, interbacterial interactions and other internal and external factors alter the environment to a point where it no longer does.
Keeping Up the Momentum
What continues to make sense is sustained scientific investigation into the molecular machinations of bacterial adhesion, migration and every behavior in between. Some of these insights have clear potential applications. For example, Luallen highlighted that his lab’s work could someday help scientists better engineer bacteria to become part of the microbiome. Meanwhile, Herr’s research could help keep skin healthy.
But the benefits of such fundamental discoveries extend beyond clear translational impact. Wadhwa noted that swashing may not be immediately useful. However, that doesn’t mean it never will be. “I think that we simply never know where a critical finding is going to come from that is going to solve a major problem for humanity,” he said. “If we are to find new approaches, I think we have to do this kind of curiosity-based research, where people are studying things without an agenda.”
Luallen also emphasized that there is inherent value to discovery. His lab works with undergraduates and high school students to collect C. elegans from the wild. Often, the students have “visceral reactions” to seeing microscopy images of the bacteria sheltered within the guts of their specimens. “That discovery arm is really fun,” he said. “I think sometimes that gets forgotten in science. [But] that’s how a lot of us got into science. Some aspect of it was fun to us.”
Studying the molecular mechanisms that govern microbial life is a lot of fun—and so is sharing your discoveries with your peers. If you research microbial mechanisms, connect with your community and join us at the ASM Mechanism Discovery Meeting at ASM Microbe 2026 in Washington, D.C., June 4-7.
Author: Madeline Barron, Ph.D.
In This Issue
- Why Does Basic Science Research Matter?
- The Value of Curiosity-Driven Research: Mechanism Discovery With Glen McGugan
- Stuck on You: How Bacteria Migrate and Adhere to Their Hosts
- Cable Bacteria: Electric Marvels of the Microbial World
- Can't Sleep? Your Microbiome May Play a Role
- How Spatial Structure Shapes Microbial Communities
- Plasmids and the Spread of Antibiotic Resistance Genes
- From Mpox to Measles: Why Viruses Cause Lesions and Rashes
- Bringing Microbial Dark Matter Into the Light