Intracellular activity of PBTZ169 against <i>Nocardia brasiliensis</i> HUJEG-1 after 8 h of replication inside THP-1 macrophages.

<p>The measurements were performed in triplicate. Each point represents the mean of the assays and error bars represent the standard deviations. There were significant differences at all concentrations for PBTZ169 (open diamonds) (<i>P</i>  =  0.021) (MIC = 0.0037 μg/mL). As a control, we used tedizolid (closed circles) (MIC = 8 μg/mL).</p

Alignment of <i>M</i>. <i>tuberculosis</i> DprE1 ortholog proteins in <i>Nocardia spp</i>. We observe that all species have orthologs with the susceptible genotype, a cysteine at position 368.

<p>This analysis included common <i>Nocardia</i> pathogens, such as <i>N</i>. <i>brasiliensis</i>, <i>N</i>. <i>cyryiacigeorgica</i>, <i>N</i>. <i>farcinica</i>, <i>N</i>. <i>transvalensis</i>, and <i>N</i>. <i>otitidiscaviarum</i>. We also included rarely pathogenic species, such as <i>N</i>. <i>tenerifensis</i>, <i>N</i>. <i>terpenica</i>, and <i>N</i>. <i>carnea</i>.</p

Plasma levels observed in BALB/c mice after applying, by gavage, PBTZ169 (left) and trimethoprim-sulfomethoxazole (right), both at 100 mg/kg.

<p>Three mice were bled and sacrificed at each point. Bars represent the standard deviation.</p

Effect of PBTZ169, BTZ043, and SXT on the development of mycetoma lesions in BALB/c mice infected with <i>N</i>. <i>brasiliensis</i> HUJEG-1.

<p>The Y axis is an arbitrary scale we developed to measure the degree of infection (14) and goes from the total absence of lesions (0.0 +) to the presence of abundant inflammation, abscesses and fistulae. Each dot represents the reading of one animal; all the groups were compared statistically against the saline control group by using the Variance test,. According to this analysis, significant differences were found for treatment with PBTZ169 (<i>P</i> = 0.017) but not BTZ043 (<i>P</i> = 0.667). The positive control group treated with SXT yielded a statistically significant value (<i>P</i> = 0.007).</p

Protein sequence alignment of <i>M</i>. <i>tuberculosis</i> H37Rv DprE1 (A) and two orthologs in the genome of <i>N</i>. <i>brasiliensis</i> HUJEG-1.

<p>In red, we show Cys387. B: <i>N</i>. <i>brasilie</i>nsis YP_006807368 has 97% query cover and 62% identity to MTB DprE1. C: <i>N</i>. <i>brasiliensis</i> YP_006805098, presents a 99% query cover and 74% identity to MTB DprE1.</p

Plasma levels of BTZ043 observed in BALB/c mice.

<p>Animals were given SXT at 100 mg/kg by gavage. Each point represent the mean of three mice with bars representing the standard deviation obtained.</p

ELISA detection of anti-HspX IgM and IgG in serum of re-classified individuals.

<p>Optical densities (492 nm) of IgM (A) or IgG antibodies (B) against recombinant HspX in persons classified as active TB, unknown, uninfected, LTBI or rLTBI.</p

Detection of anti- HspX IgM and IgG in human sera by ELISA.

<p>Optical densities (492 nm) of IgM (A) or IgG antibodies (B) against recombinant HspX protein in individuals classified as active TB, unknown, uninfected and LTBI.</p