Fig 1.
Disconnect between sites of parasite persistence and metabolic alterations in chronic cardiac CD.
(A) Median cardiac parasite burden, as determined by qPCR. Parasite burden was highest at the heart base (position A) for strain CL and central heart segments (position C) for strain Sylvio X10/4, indicating parasite strain-specific differences in parasite tropism. (B) Statistically significant perturbations in the overall metabolite profile between uninfected and strain CL-infected mice (left), and between uninfected and strain Sylvio X10/4-infected mice (right). The highest significant metabolite perturbation was at central heart segments (position C) for strain CL (***, p < 0.001 by PERMANOVA) and at the heart apex (position D) for strain Sylvio X10/4 (**, p < 0.01 by PERMANOVA).
Fig 2.
Limited overlap of specific differential metabolites between strains.
Yellow and red circles represent differential metabolites between strain Sylvio X10/4-infected and matched uninfected controls, and between strain CL-infected and matched uninfected controls, respectively. Intersect are metabolites impacted by infection in both strains. (A-D) Differential metabolites for each strain, at given heart positions, as determined by random forest classifier, with variable importance score cutoff as described in Methods. (E) Metabolites impacted by infection with each strain, irrespective of position, as determined by random forest classifier, with variable importance score cutoff as described in Methods. (F) Metabolites impacted by infection with each strain, irrespective of heart position, using FDR-corrected Mann Whitney p<0.05 cutoff.
Fig 3.
Spatial impact of chronic T. cruzi infection on cardiac acylcarnitines.
Normal levels and distribution of acylcarnitines are represented by uninfected samples. (A, B) Differential total acylcarnitine distribution between uninfected and infected heart sections for both CL and Sylvio X10/4 strains. CL-infected mice showed statistically significant decreases in total acylcarnitine levels at heart base when compared to uninfected mice (*, p<0.05 by Mann-Whitney test). (C, D) CL-infected mice showed statistically significant decreases (*, p<0.05, by Mann-Whitney test) in short-chain acylcarnitine (≤ C4) at heart base. (E, F) Sylvio X10/4-infected mice showed statistically significant decreases in mid-chain acylcarnitines at all positions compared to uninfected mice. (*, p<0.05 by Mann-Whitney test). (G, H) Sylvio X10/4-infected mice showed statistically significant decreases in long-chain acylcarnitines (≥C12) at most heart positions compared to uninfected mice (*, p<0.05 by Mann-Whitney test).
Fig 4.
Spatial impact of chronic T. cruzi infection on cardiac glycerophosphocholines.
(A, B) Differential total glycerophosphocholine distribution between uninfected and infected heart sections for both CL and Sylvio X10/4 strains. CL-infected mice showed statistically significant increases in total glycerophosphocholine levels at central heart positions when compared to uninfected mice (*, p<0.05 by Mann-Whitney test). (C,D) Both infected strains showed statistically significant increases (*, p<0.05, by Mann-Whitney test) for short glycerophosphocholines (m/z 400–599.99) at central and apical positions for strain CL and apical positions for strain Sylvio X10/4. (E, F) Mid-sized glycerophosphocholines (m/z 600–799.99) were not significantly affected by infection for both strains. (G, H) Sylvio X10/4-infected mice showed a statistically significant increase (*, p<0.05 by Mann-Whitney test) in long glycerophosphocholines (m/z> 800) at apical positions.