Unmasking the Molecular Battle: How Coinfection with Lyme Disease and Babesiosis Reshapes Our Bodies

Tick-borne illnesses are a growing global concern, and in regions like the northeastern U.S., it's increasingly common for ticks to transmit more than one pathogen in a single bite. Two such culprits are Babesia microti (Bm), which causes a malaria-like illness called babesiosis, and Borrelia burgdorferi, the spirochete responsible for Lyme disease. While individually problematic, coinfection with these two pathogens often leads to more severe Lyme disease symptoms than B. burgdorferi infection alone. Despite this, how our bodies respond at a molecular level during these coinfections has largely remained a mystery.

            The Parveen Lab, New Jersey Medical School, sheds light on this complex interplay by investigating the temporal dynamics of the host proteome—the entire set of proteins expressed by an organism—in mice infected with Bm, B. burgdorferi, or both.

            The lab used a susceptible C3H mouse model, monitoring B. burgdorferi infection through live imaging and Bm parasitemia via blood smears. They then performed comprehensive proteomic analyses of blood samples at 2, 4, and 16 weeks post-infection to capture the acute, resolving, and persistent stages of the diseases.

The findings revealed distinct changes in the mouse proteome over time:

• Early Phase (2 weeks):

  • The coinfected group (B. burgdorferi +Bm) showed the most pronounced differences in protein profiles compared to uninfected mice, highlighting a unique host response to the dual infection.

  • Proteins associated with cellular and metabolic processes were significantly upregulated, particularly in coinfected mice, demonstrating a rapid increase (more than 2-fold higher than Bm alone) in these vital functions.

  • A significant number of proteins related to immune system processes were also altered in the coinfection group, underscoring the complex immune responses at play.

  • In Bm-infected mice, researchers observed elevated levels of hemoglobin-related proteins, suggesting acute hemolysis—a hallmark of Babesia infection. In contrast, coinfected mice showed an early increase in T-cell markers and immunoglobulins, indicating accelerated adaptive immune recruitment.

• Mid-Phase (4 weeks):

  • A significant convergence in host responses between the Bm and coinfected groups was observed, with a much higher overlap of proteins compared to the 2-week mark. This suggests that after the peak of Bm parasitemia, the host's protein expression starts to equilibrate.

  • Cellular and metabolic processes remained highly active in both infected groups, with the Bm-only group showing a greater increase.

  • Immune system proteins were notably higher in the Bm group compared to the coinfection group at this stage, more than double the levels seen at 2 weeks post-infection.

  • Splenomegaly (enlarged spleen) was pronounced in both Bm and coinfected mice, especially at 4 weeks, correlating with high parasitemia and the spleen's role in clearing infected red blood cells.

• Persistent Phase (16 weeks):

  • Despite diminished pathogen levels, a profound shift in the host proteome persisted, significantly departing from the naive group. This highlights the enduring impact of these infections on the host's biological processes.

  • The overlap between Bm and coinfected mice's proteomes reduced significantly, suggesting divergent trajectories in host responses and a resolution of some early-stage gene expression.

  • While cellular and metabolic proteins remained upregulated compared to naive mice, their numbers were significantly lower than at 4 weeks, indicating a partial return to equilibrium as pathogen levels decreased.

  • Notably, in coinfected mice, elevated levels of immunoglobulins and complement factors remained, pointing towards chronic immune stimulation, a pattern also seen in persistent Lyme disease.

            Beyond tracking host responses, the study also successfully identified and tracked limited numbers of Bm proteins at all stages of infection. The detection of Bm proteins, even at 16 weeks (the persistent phase), underscores the parasite's sustained presence. This finding confirms the known fact that asymptomatic parasite human carriers can transmit this infection through blood transfusion, causing havoc in unsuspecting, hospitalized patients if donor’s blood is not tested for Babesia.

            This study provides insights into the molecular interplay between host and microbes during Babesia microti and Borrelia burgdorferi coinfection. By illustrating the dynamic shifts in the host proteome over time, it offers a platform for future research aimed at developing targeted diagnostics and therapeutic interventions for these challenging tick-borne diseases. While the pooled sample strategy allowed for the detection of low-abundance proteins, future studies incorporating biological replicates will be essential for the statistical validation of these findings.

Moustafa MAM, Rocha SC, Velásquez CV, Parveen N. Temporal Dynamic Interplay of Mouse Proteome during Protozoan Babesia microti Infection Alone or with Borrelia burgdorferi Coinfection. J Proteome Res. 2025 Jul 4;24(7):3286-3299. doi: 10.1021/acs.jproteome.5c00015. Epub 2025 Jun 20. PMID: 40541258; PMCID: PMC12235692.

https://pubs.acs.org/doi/10.1021/acs.jproteome.5c00015