Spoligotype tree of <i>M. tuberculosis</i> isolates (n = 68).

<p>Lineage, Spoligotype International Type (SIT) as defined in the SITVITWEB proprietary database of the Pasteur Institute of Guadeloupe, and the strain identifications are shown.</p

IS6110-RFLP clustering patterns, spoligopatterns and drug resistance profiles of <i>M. tuberculosis</i> isolates.

<p>Drug resistance profile indicates resistance to I: isoniazid; R: rifampicin; S: streptomycin and E: ethambutol.</p

Description of shared types found in this study.

<p>^<i>a</i>In the SITVITWEB database, the spoligo (shared) international type (SIT) numbers designate spoligotypes shared by two or more patient isolates.</p><p>*SIT3434 is a newly created shared type due to two strains belonging to a new pattern within this study.</p><p>^<i>b</i>Clade designations according to the SITVITWEB database: Beijing clade, East African-Indian (EAI) clade and 9 sublineages, Haarlem (H) clade and 3 sublineages, Latin American-Mediterranean (LAM) clade and 12 sublineages, the ancestral “Manu” family and 3 sublineages, the S clade, the IS<i>6110</i>-low-banding X clade and 3 sublineages, and an ill-defined T clade with 5 sublineages. Unk, unknown patterns within any of the major clades described in the database.</p><p>Description of shared types found in this study.</p

Description of orphan strains found in this study.

<p>Orphan strains had spoligotype patterns that did not match a preexisting pattern in the SITVITWEB database.</p><p>Description of orphan strains found in this study.</p

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

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

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 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

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