Complete mitochondrial genome of Gnathostoma binucleatum.

This report describes the mitochondrial genome of the parasite Gnathostoma binucleatum (G. binucleatum), which was obtained from naturally infected freshwater fish in Sinaloa, Mexico (22°46'00.1″N 105°40'21.8″W). G. binucleatum is responsible for human gnathostomiasis and is endemic to Mexico. It belongs to the Spirurida order of the Secernentea class of Nematoda.

Correction: Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

[This corrects the article DOI: 10.1371/journal.pntd.0009145.].

Cu,Zn superoxide dismutase: cloning and analysis of the Taenia solium gene and Taenia crassiceps cDNA.

Cytosolic Cu,Zn superoxide dismutase (Cu,Zn-SOD) catalyzes the dismutation of superoxide (O(2)(-)) to oxygen and hydrogen peroxide (H(2)O(2)) and plays an important role in the establishment and survival of helminthes in their hosts. In this work, we describe the Taenia solium Cu,Zn-SOD gene (TsCu,Zn-SOD) and a Taenia crassiceps (TcCu,Zn-SOD) cDNA. TsCu,Zn-SOD gene that spans 2.841 kb, and has three exons and two introns; the splicing junctions follow the GT-AG rule. Analysis in silico of the gene revealed that the 5'-flanking region has three putative TATA and CCAAT boxes, and transcription factor binding sites for NF1 and AP1. The transcription start site was a C, located at 22 nucleotides upstream of the translation start codon (ATG). Southern blot analysis showed that TcCu,Zn-SOD and TsCu,Zn-SOD genes are encoded by a single copy. The deduced amino acid sequences of TsCu,Zn-SOD gene and TcCu,Zn-SOD cDNA reveal 98.47% of identity, and the characteristic motives, including the catalytic site and ß-barrel structure of the Cu,Zn-SOD. Proteomic and immunohistochemical analysis indicated that Cu,Zn-SOD does not have isoforms, is distributed throughout the bladder wall and is concentrated in the tegument of T. solium and T. crassiceps cysticerci. Expression analysis revealed that TcCu,Zn-SOD mRNA and protein expression levels do not change in cysticerci, even upon exposure to O(2)(-) (0-3.8 nmol/min) and H(2)O(2) (0-2mM), suggesting that this gene is constitutively expressed in these parasites.

Intra-host genetic population diversity: Role in emergence and persistence of drug resistance among Mycobacterium tuberculosis complex minor variants.

Drug resistant tuberculosis (DR-TB) is an important public health issue in different parts of the world. Mycobacterium tuberculosis complex variants (MTBC vars) preferentially infect certain hosts, limiting their distribution to different ecosystems. However, MTBC vars can infect other hosts beyond their preferred target potentially contributing to persistence of drug resistance (DR) in other niches. Here, we performed a comprehensive intra-host genetic analysis for the identification of DR-related mutations among all MTBC minor vars whole genome sequences (8,095 strains) publicly available worldwide. High confidence drug-resistance mutations in katG (isoniazid), rpsL (streptomycin), pncA (pyrazinamide), rpoB (rifampicin) and gyrA (fluoroquinolones) genes were identified among intrahost minor sub-populations in 197 different strains (2.43%) belonging to vars africanum, bovis, caprae, microti, orygis and pinnipedii. In addition, a three-dimensional structure modeling analysis to assess the role of novel mutations was also performed. Our findings highlight the importance of detecting discrete intra-host populations carrying DR mutations.

Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

Identifying the Mycobacterium tuberculosis resistance mutation patterns is of the utmost importance to assure proper patient's management and devising of control programs aimed to limit spread of disease. Zoonotic Mycobacterium bovis infection still represents a threat to human health, particularly in dairy production regions. Routinary, molecular characterization of M. bovis is performed primarily by spoligotyping and mycobacterial interspersed repetitive units (MIRU) while next generation sequencing (NGS) approaches are often performed by reference laboratories. However, spoligotyping and MIRU methodologies lack the resolution required for the fine characterization of tuberculosis isolates, particularly in outbreak settings. In conjunction with sophisticated bioinformatic algorithms, whole genome sequencing (WGS) analysis is becoming the method of choice for advanced genetic characterization of tuberculosis isolates. WGS provides valuable information on drug resistance and compensatory mutations that other technologies cannot assess. Here, we performed an analysis of the most frequently identified mutations associated with tuberculosis drug resistance and their genetic relationship among 2,074 Mycobacterium bovis WGS recovered primarily from non-human hosts. Full-length gene sequences harboring drug resistant associated mutations and their phylogenetic relationships were analyzed. The results showed that M. bovis isolates harbor mutations conferring resistance to both first- and second-line antibiotics. Mutations conferring resistance for isoniazid, fluoroquinolones, streptomycin, and aminoglycosides were identified among animal strains. Our findings highlight the importance of molecular surveillance to monitor the emergence of mutations associated with multi and extensive drug resistance in livestock and other non-human mammals.

Characterization of one typical 2-Cys peroxiredoxin gene of Taenia solium and Taenia crassiceps.

The Taenia genus is capable of living for long periods within its hosts. Reports have shown that this successful establishment is related to its efficient defense mechanisms against host immune response and its high tolerance to oxidative stress. In this work, we describe the genomic sequences of one Taenia solium and Taenia crassiceps typical 2-Cys peroxiredoxins (Ts2-CysPrx, Tc2-CysPrx) genes, which are 94% identical in primary sequence with the typical 2-Cys Prxs catalytic motifs. Both genes have the same genomic architecture, showing a TATA box and Initiator (Inr) sequence in their proximal promoter, two exons split by a 67-bp type III intron and one unique transcription start site located inside the Inr. We show that T. crassiceps cysticerci are highly tolerant to H(2)O(2) presenting a lethal concentration 50 of 3.0 mM and demonstrate that the typical Tc2-CysPrx gene is not induced by H(2)O(2), showing a behavior of an antioxidant housekeeping gene. This study describes for first time the gene structure of a typical 2-Cys Prx in the Taenia genus.

Crystal structure of Cu / Zn superoxide dismutase from Taenia solium reveals metal-mediated self-assembly.

Taenia solium is the cestode responsible for porcine and human cysticercosis. The ability of this parasite to establish itself in the host is related to its evasion of the immune response and its antioxidant defence system. The latter includes enzymes such as cytosolic Cu/Zn superoxide dismutase. In this article, we describe the crystal structure of a recombinant T. solium Cu/Zn superoxide dismutase, representing the first structure of a protein from this organism. This enzyme shows a different charge distribution at the entrance of the active channel when compared with human Cu/Zn superoxide dismutase, giving it interesting properties that may allow the design of specific inhibitors against this cestode. The overall topology is similar to other superoxide dismutase structures; however, there are several His and Glu residues on the surface of the protein that coordinate metal ions both intra- and intermolecularly. Interestingly, one of these ions, located on the ß2 strand, establishes a metal-mediated intermolecular ß-ß interaction, including a symmetry-related molecule. The factors responsible for the abnormal protein-protein interactions that lead to oligomerization are still unknown; however, high metal levels have been implicated in these phenomena, but exactly how they are involved remains unclear. The present results suggest that this structure could be useful as a model to explain an alternative mechanism of protein aggregation commonly observed in insoluble fibrillar deposits.

Evaluación del antibiótico miocamicina en niños con infecciones bacterianas cutáneas / Evaluation of the miocarmycin antibiotic in children with bacterial skin infecctions

Se llevó a cabo un ensayo clínico prospectivo abierto con 42 niños que sufrían de enfermedades de la piel, para verificar la eficacia y tolerancia de la Miocamicina, un nuevo antibiótico-macrólido. Se incluyeron 31 casos con impétigo, 5 forunculosis y 6 foliculitis con edades comprendidas entre 1 mes hasta 12 años de edad. De éstos, 27 fueron niñas y 15 niños, promedio de edad 3,3 años. La duración del tratamiento fue de 10 días, a una dosis oral de 30-50 mg/Kg/día. la suspensión de Miocamicina contenía 200 mg/5 ml. Se encontraron 30 aislados bacterianos con alta sensibilidad a la Miocamicina, 2 casos de sensibilidad intermedia y 10 casos con mediana resistencia, la mayoría de los cuales fueron Staphylococcus aureus. Los resultados clínicos mostraron porcentaje de éxito terapéutico equivalente a 90,32 por ciento dentro del grupo de 31 pacientes con impétigo. Asi mismo curaron completamente 3 forunculosis de un grupo de 6 casos, en tanto que 2 mejoraron parcialmente. Por su parte, se logró exito terapéutico total en 50 por ciento de los casos de foliculitis. Del grupo total de 42 pacientes, en 2 no se modificó la patología y 4 empeoraron. Estos datos totalizan un promedio de curación completa, para las 3 piodermias indicadas, equivalente a 85,71 por ciento. Los efectos secundarios se presentaron sólo en 2 casos y consistieron en diarrea ligera y pérdida de apetito, hecho que nos da una tolerancia del 95,23 por ciento