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Mar 23

Round bodies, blebs and biofilms in Lyme disease

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Can Borrelia burgdorferi Form Biofilms? New Research on Lyme Bacterial Forms

Borrelia biofilms and other bacterial forms have been identified in laboratory studies
Researchers are investigating whether they contribute to bacterial persistence
Their role in human Lyme disease remains under investigation

Borrelia burgdorferi, the bacterium that causes Lyme disease, is best known for its spiral (spirochete) shape. However, laboratory studies have shown that it can also adopt other forms, including round bodies, membrane blebs, and biofilm-like communities. Researchers continue to investigate whether these alternative forms help the bacteria survive environmental stress, persist within the host, or influence treatment response.

In an effort to better understand these bacterial forms, Corak and colleagues grew B. burgdorferi under different laboratory conditions and analyzed gene expression using RNA sequencing (RNA-seq). By simply altering culture conditions, the investigators generated spirochetes, round bodies, blebs, and biofilm-dominated cultures and compared how each form expressed its genes.

These different bacterial forms represent examples of Borrelia morphology, or the organism’s ability to change its physical structure under different environmental conditions. The morphologic forms described in this study were generated under laboratory culture conditions, and researchers continue to investigate whether similar forms develop during human infection.

What are the different Borrelia burgdorferi forms?

The investigators described three non-spirochetal forms commonly observed in laboratory cultures.

  1. Round bodies. These spherical forms retain an intact and flexible cell envelope enclosing multiple flagella. They are often referred to as “round bodies.”
  2. Blebs. This form is characterized by the production of outer membrane vesicles (OMVs) that bud from the bacterial surface.
  3. Biofilms. Biofilms are multicellular communities containing spirochetes, round bodies, and bleb forms embedded within a self-produced extracellular matrix.

What did the researchers discover?

Round bodies showed gene expression patterns that were remarkably similar to the familiar spirochete form. In contrast, blebs and biofilms demonstrated substantially different transcriptomic profiles, suggesting that these forms may have distinct biological functions.

The authors proposed that these differences could reflect specialized adaptations that help B. burgdorferi respond to environmental stress. They also suggested that blebs and biofilms deserve additional study because they may play a role in bacterial dissemination or persistence within mammalian hosts.

Corak and colleagues concluded:

“These regularities point to the possibility that bleb and biofilm morphotypes might be important in the dissemination and persistence of B. burgdorferi inside the mammalian host.”

These findings naturally raise an important clinical question: could Borrelia biofilms contribute to persistent Lyme disease in humans?

Do Borrelia biofilms explain persistent Lyme disease?

Laboratory studies have demonstrated that Borrelia burgdorferi can form biofilm-like communities under experimental conditions. Whether these structures contribute to persistent infection or ongoing symptoms in humans remains uncertain. Investigators continue to study their biological significance, but additional animal and human research is needed before firm clinical conclusions can be drawn.

These laboratory findings have generated considerable scientific interest because they may improve our understanding of how Borrelia burgdorferi adapts to environmental stress and survives under adverse conditions. However, the clinical significance of these morphologic forms remains an active area of investigation.

Why this research matters

Understanding how Borrelia burgdorferi adapts to different environments may help explain why Lyme disease can present so differently among patients. Future studies may clarify whether these bacterial forms contribute to persistence, immune evasion, treatment response, or other aspects of Lyme disease pathogenesis and could identify new therapeutic targets.

The investigators summarized the broader implications of their work:

“Taken together, we believe that many of the ongoing controversies related to Lyme disease pathogenesis and treatment strategies could be resolved by improving our understanding of B. burgdorferi biology and evolution.”

Frequently Asked Questions

Can Borrelia burgdorferi form biofilms?

Yes. Laboratory studies have shown that Borrelia burgdorferi can form biofilm-like communities under experimental conditions. Researchers continue to investigate whether similar structures develop during human infection and what role they may play in Lyme disease.

What are Borrelia round bodies?

Round bodies are spherical forms of Borrelia burgdorferi that retain an intact cell envelope and internal flagella. In this study, they displayed gene expression patterns that were similar to the classic spirochete form.

Do Borrelia biofilms explain chronic Lyme disease?

Not yet. Laboratory research suggests that biofilms may help bacteria adapt to stressful conditions, but there is currently insufficient evidence to conclude that biofilms are responsible for persistent symptoms in patients with Lyme disease.

Should patients follow a Lyme biofilm protocol?

Although biofilm-targeting therapies are widely discussed, there are currently no evidence-based clinical guidelines recommending routine “biofilm protocols” for Lyme disease. Treatment decisions should be individualized based on the patient’s clinical presentation and the best available scientific evidence.

Clinical Takeaway

Laboratory evidence supports the existence of multiple Borrelia burgdorferi morphologic forms, including biofilms, round bodies, and blebs. These findings have expanded our understanding of Lyme disease biology and have prompted further investigation into bacterial persistence.

There is currently no validated clinical test to identify Borrelia biofilms in patients, and treatment decisions should be guided by the patient’s overall clinical presentation rather than the presumed presence of biofilms.

Although laboratory studies have identified several Borrelia morphologic forms, their precise role in human Lyme disease remains an active area of investigation.

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References
  1. Corak A, et al. Pleomorphic Variants of Borreliella (syn. Borrelia) burgdorferi Express Evolutionary Distinct Transcriptomes. Int J Mol Sci. 2023;24(6):5594.
  2. Sapi E, Bastian SL, Mpoy CM, et al. Characterization of biofilm formation by Borrelia burgdorferi in vitro. PLoS One. 2012;7:e48277.
  3. Verschoor YL, Vrijlandt A, Spijker R, van Hest RM, ter Hofstede HJM, Hovius JW. Persistent Borrelia burgdorferi sensu lato Infection after Antibiotic Treatment: Systematic Overview and Appraisal of the Current Evidence from Experimental Animal Models. Clin Microbiol Rev. 2022;35(4):e00074-22.

Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

SymptomsTestingCoinfectionsRecoveryPediatricPrevention

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2 thoughts on “Round bodies, blebs and biofilms in Lyme disease”

  1. I was the first to describe Round body form borrelia( cystic form)
    in 1988. I am delighted to read your update from researchers in Croatia and Germany who describe on detail the molecular basis of cystic borrelia, and blebs of borrelia and biofilm borrelia communities.
    Each “ variant” non spiral form of borrelia carry a molecular signature which differs from the “spiral “ form Gene expressions. These molecular signatures influence the synthesis of key “ variant” proteins
    and provide an explanation for the failure of current serology test kits to detect these “ variant “ proteins.

    Alan B MacDonald MD

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