Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Emerging infectious disease implications of invasive mammalian species : the greater white-toothed shrew (Crocidura russula) is associated with a novel serovar of pathogenic Leptospira in Ireland

The greater white-toothed shrew (Crocidura russula) is an invasive mammalian species that was first recorded in Ireland in 2007. It currently occupies an area of approximately 7,600 km2 on the island. C. russula is normally distributed in Northern Africa and Western Europe, and was previously absent from the British Isles. Whilst invasive species can have dramatic and rapid impacts on faunal and floral communities, they may also be carriers of pathogens facilitating disease transmission in potentially naive populations. Pathogenic leptospires are endemic in Ireland and a significant cause of human and animal disease. From 18 trapped C. russula, 3 isolates of Leptospira were cultured. However, typing of these isolates by standard serological reference methods was negative, and suggested an, as yet, unidentified serovar. Sequence analysis of 16S ribosomal RNA and secY indicated that these novel isolates belong to Leptospira alstonii, a unique pathogenic species of which only 7 isolates have been described to date. Earlier isolations were limited geographically to China, Japan and Malaysia, and this leptospiral species had not previously been cultured from mammals. Restriction enzyme analysis (REA) further confirms the novelty of these strains since no similar patterns were observed with a reference database of leptospires. As with other pathogenic Leptospira species, these isolates contain lipL32 and do not grow in the presence of 8-azagunaine; however no evidence of disease was apparent after experimental infection of hamsters. These isolates are genetically related to L. alstonii but have a novel REA pattern; they represent a new serovar which we designate as serovar Room22. This study demonstrates that invasive mammalian species act as bridge vectors of novel zoonotic pathogens such as Leptospira

An integrated cell atlas of the lung in health and disease

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP

An integrated cell atlas of the lung in health and disease

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Detección de los genes mecA, mecR1 y mecI en cepas de Staphylococcus aureus resistentes a meticilina de origen bovino aisladas en unidades de producción lechera familiar, México

En México como en otros países, Staphylococcus aureus es uno de los principales patógenos causantes de mastitis bovina. El tratamiento de esta enfermedad se realiza principalmente con antibióticos β -lactámicos; sin embargo, en México existen estudios de Staphylococcus aureus resistente a este tipo de antibióticos, actualmente los mecanismos moleculares de Staphylococcus aureus resistente a meticilina no han sido ampliamente estudiados. En este trabajo se identificó Staphylococcus aureus aislados de bovinos mediante la detección del gen femB , utilizando ambos métodos, microbiológicos convencionales y moleculares. La resistencia a los antibióticos β -lactámicos fue determinada por pruebas de susceptibilidad antimicrobiana in vitro y por PCR de los genes blaZ , mecA y los genes reguladores mecR1 y mecI . Los resultados mostraron una mayor resistencia de Staphylococcus aureus a los antibióticos β -lactámicos y a la eritromicina, solamente 38 (44,7%) de los aislamientos fueron positivos al gen blaZ . Por otro lado, cuatro Staphylococcus aureus fueron positivos al gen mecA considerados como SARM, los que por la detección de sus genes reguladores se agruparon de la siguiente forma: uno fue positivo a los genes mecI y mecR1 (grupo A), dos no presentaron el gen mecI ni el dominio PB del gen mecR1 (grupo C) y uno no mostró ningún gen regulador (grupo D). En conclusión, se identificó la presencia de Staphylococcus aureus resistente a la meticilina en unidades de producción lechera familiar en el estado de México, y su resistencia a los antibióticos β -lactámicos. Esta resistencia podría estar regulada por diferentes genotipos de los genes mecA , mecR1 y mecI presentes en Staphylococcus aureus resistente a la meticilina

Trichoderma harzianum in vitro mycoparasitism on Peronospora belbahrii in basil (Ocimum basilicum)

Mildew (Peronospora belbahrii) is the disease that, worldwide, causes the greatest loss in the production of basil (Ocimum basilicum). The objective of the present work was to describe the symptoms and identification the causal agents of the mildiu in basil, as well as the evaluation of the antagonism in vitro of Trichoderma harzianum-P. belbahrii. For this, samples of basil plants, cultivar Nufar, with natural infection by mildew were taken. P. belbahrii was isolated from basil plants and later antagonism tests were carried out in sterile PDA-based culture medium, in Petri dishes. The ability of T. harzianum to parasitize P. belbahrii in vitro, could be appreciated after 72 hours, when the antagonist conidium germinated, the hyphae directed their chemotrophic growth towards the conidiophores and mycelium of P. belbahrii. Subsequently, the Trichoderma hyphae began to coil, penetrate, vacuolate the conidiophores and mycelium of the pathogen.Objective: To describe the symptomatology and to identify the mildew causal agent in basil (Oscimum basilicum), as well as the Trichoderma harzianum-Peronospora belbahrii in vitro mycoparasitic activity. Design/methodology/approach: Samples were taken from Nufar basil cultivars that had been naturally infected by mildew and, afterwards, the causal agent was isolated in order to carry out a pathogenicity test. The T. harzianum-P. belbahrii parasitism stages were observed in samples from the area in which both microorganisms interact. Results: The disease symptoms that reveal the presence of a mildew causal agent on basil plants grown in pots and soil match Peronospora belbahrii. Subsequently, the Trichoderma hyphae rolled up and penetrated and vacuolated the conidiophores and the pathogen mycelium. Study limitations/implications: This study was carried out using only one variety of basil. Findings/conclusions: T. harzianum’s capacity to parasitize P. belbahrii in vitro was observed after 72 h. Once the conidium of the antagonist germinated, the hyphae directed their chemotropism growth towards P. belbahrii’s conidiophores and mycelium

Determination of extended spectrum β-lactamases/AmpC β-lactamases and plasmid-mediated quinolone resistance in Escherichia coli isolates obtained from bovine carcasses in Mexico

Food-borne bacterial infections have worldwide importance, and a great variety of antibiotic resistance mechanisms, mainly of the chromosome type, have rapidly developed. Antimicrobial resistance was determined in this study in terms of the presence of extended-spectrum β-lactamases (ESBLs), plasmid AmpC β-lactamases (pAmpC), and plasmid-mediated quinolone resistance (PMQR) from 155 Escherichia coli isolates obtained from bovine carcasses from two states in Mexico (states of Mexico and Jalisco). Isolates were challenged with β-lactam antimicrobials (ampicillin, ceftazidime, and cefotaxime) and quinolones (nalidixic acid and ciprofloxacin). The presence of the blaTEM, blaSHV, blaCTX-M, blaOXA, blaCMY, blaMOX, blaLAT, blaBIL, qnrA, qnrB, qnrS, aac(6′)-Ib-cr, and qepA genes was examined by PCR. Clonal relationship was determined using pulsed-field gel electrophoresis (PFGE). The highest resistance was found to be to nalidixic acid (64 %), followed by ampicillin (32 %), ciprofloxacin (10 %), and ceftazidime and cefotaxime (both 1.3 %). blaCMY (n = 1), blaTEM (n = 24), qnrB (n = 9), and qnrS (n = 7) genes were detected. PFGE analysis showed that the majority of isolates had a different genotypic profile. To our knowledge, this is the first report of the presence of the qnrB, qnrS, and blaCMY genes in E. coli isolated from bovine meat in Mexico. © 2015 Springer Science+Business Media Dordrech