Sideromimic Modification of Lactivicin Dramatically Increases Potency against Extensively Drug-Resistant <i>Stenotrophomonas maltophilia </i>Clinical Isolates

Acetamido derivatives of the naturally antibacterial non-β-lactam lactivicin (LTV) have improved activity against their penicillin binding protein targets and reduced hydrolysis by β-lactamases, but penetration into Gram-negative bacteria is still relatively poor. Here we report that modification of the LTV lactone with a catechol-type siderophore increases potency 1,000-fold against Stenotrophomonas maltophilia, a species renowned for its insusceptibility to antimicrobials. The MIC90 of modified lactone compound 17 (LTV17) against a global collection of extensively drug-resistant clinical S. maltophilia isolates was 0.063 μg · ml(-1) Sideromimic modification does not reduce the ability of LTVs to induce production of the L1 and L2 β-lactamases in S. maltophilia and does not reduce the rate at which LTVs are hydrolyzed by L1 or L2. We conclude, therefore, that lactivicin modification with a siderophore known to be preferentially used by S. maltophilia substantially increases penetration via siderophore uptake. LTV17 has the potential to be developed as a novel antimicrobial for treatment of infections by S. maltophilia More generally, our work shows that sideromimic modification in a species-targeted manner might prove useful for the development of narrow-spectrum antimicrobials that have reduced collateral effects

Case report: First report on human infection by tick-borne Babesia bigemina in the Amazon region of Ecuador.

Babesiosis is a protozoan disease acquired by the bite of different species of ticks. More than 100 Babesia spp. infect wild and domestic animals worldwide, but only a few have been documented to infect humans. Generally, babesiosis is asymptomatic in immunocompetent persons; however, in immunocompromised can be life-threatening. A 13-year-old boy from the Amazon region presented with a 3-month evolution of fever, chills, general malaise, and arthralgia accompanied by anemia and jaundice. In the last 4 years was diagnosed with chronic kidney failure. By nested-PCR using 18S RNA ribosomal gene as target and DNA sequencing, the phylogenetic analysis showed Babesia bigemina as the causative agent in the blood. Treatment with oral quinine plus clindamycin for six continuous weeks was effective with no relapse occurring during 12 months of follow-up. This is the second human case in Ecuador but the first caused by the zoonotic B. bigemina which confirms the existence of active transmission that should alert public health decision-making authorities on the emergence of this zoonosis and the need for research to determine strategies to reduce tick exposure

Epidemiology of giardiasis and assemblages A and B and effects on diarrhea and growth trajectories during the first 8 years of life: Analysis of a birth cohort in a rural district in tropical Ecuador.

BACKGROUND: There are limited longitudinal data on the acquisition of Giardia lamblia infections in childhood using molecular assays to detect and type assemblages, and measure effects of infections on diarrhea risk and childhood growth. METHODS: We analysed stool samples from a surveillance sample within a birth cohort in a rural district in tropical Ecuador. The cohort was followed to 8 years of age for the presence of G. lamblia in stools by quantitative PCR and A and B assemblages by Taqman assay or Sanger sequencing. We explored risk factors associated with infection using generalized estimating equations applied to longitudinal binary outcomes, and longitudinal panel data analysis to estimate effects of infection on diarrhea and growth trajectories. RESULTS: 2,812 stool samples collected between 1 month and 8 years of age from 498 children were analyzed and showed high rates of infection: 79.7% were infected at least once with peak prevalence (53.9%) at 5 years. Assemblage B was accounted for 56.8% of genotyped infections. Risk factors for infection included male sex (P = 0.001), daycare attendance (P<0.001), having a household latrine (P = 0.04), childhood (P<0.001) and maternal soil-transmitted helminth (P = 0.029) infections, and exposures to donkeys (age interaction P = 0.034). G. lamblia was associated with increased risk of diarrhea (per episode, RR 1.03, 95% CI 1.01-1.06, P = 0.011) during the first 3 years of life and a transient impairment of weight (age interaction P = 0.017) and height-for-age (age interaction P = 0.025) trajectories between 1 and 4 years of age. There was no increased risk of either assemblage being associated with outcomes. CONCLUSION: Our data show a relatively high edemicity of G. lamblia transmission during childhood in coastal Ecuador, and evidence that infection is associated with a transiently increased risk of diarrhea during the first 3 years of life and impairment of weight and height between 1 and 4 years

Geographic Distribution of Human Infections with Zoonotic Ancylostoma ceylanicum and Anthropophilic Hookworms in Ecuador: A Retrospective Analysis of Archived Stool Samples.

Zoonotic human infections with Ancylostoma ceylanicum have recently been reported in the Americas. We used archived human stool samples to study the geographic distribution of human infections with A. ceylanicum and anthropophilic hookworms in different geoclimatic regions (coastal, Andean, and Amazon) of Ecuador. We analyzed retrospectively archived human stool samples from five studies previously screened for hookworm infection by microscopy, of which four included hookworm-positive samples only and one involved hookworm-negative samples to increase geographic distribution of sampling. Stools were analyzed using multi-parallel quantitative polymerase chain reaction (qPCR) assays to detect Necator americanus, Ancylostoma duodenale, A. ceylanicum, Ascaris lumbricoides, Trichuris trichiura, and Strongyloides stercoralis. Sequencing was done for the A. ceylanicum cox1 gene. A total of 132 samples were analyzed, of which 69 (52.3%) were from hookworm-positive and 63 (47.7%) from hookworm-negative individuals by microscopy. Overall, 82.6% of microscopy-positive samples and 33.3% of microscopy-negative samples were positive for hookworm by qPCR. Of microscopy-positive samples, 36.2% were A. ceylanicum, 37.7% A. duodenale, and 33.3% N. americanus, whereas equivalent proportions for microscopy-negative samples were 1.6%, 31.7%, and 1.6%, respectively. Ancylostoma duodenale was the most widely dispersed geographically, followed by N. americanus. Ancylostoma ceylanicum was least dispersed but was detected in coastal and Amazon regions. In conclusion, human infections with A. ceylanicum, A. duodenale, and N. americanus were detected in different geoclimatic regions of Ecuador. Additional studies are required to further define the epidemiology of human A. ceylanicum infections, but the potentially widespread presence of this helminth in human populations in Ecuador has implications for hookworm control strategies

Profiling interactions of vaborbactam with metallo-β-lactamases

β-Lactams are the most successful antibacterials, yet their use is threatened by resistance, importantly as caused by β-lactamases. β-Lactamases fall into two mechanistic groups: the serine β-lactamases that utilise a covalent acyl-enzyme mechanism and the metallo β-lactamases that utilise a zinc-bound water nucleophile. Achieving simultaneous inhibition of both β-lactamase classes remains a challenge in the field. Vaborbactam is a boronate-based inhibitor that reacts with serine-β-lactamases to form covalent complexes that mimic tetrahedral intermediates in catalysis. Vaborbactam has recently been approved for clinical use in combination with the carbapenem meropenem. Here we show that vaborbactam moderately inhibits metallo-β-lactamases from all 3 subclasses (B1, B2 and B3), with a potency of around 20–100 fold below that by which it inhibits its current clinical targets, the Class A serine β-lactamases. This result contrasts with recent investigations of bicyclic boronate inhibitors, which potently inhibit subclass B1 MBLs but which presently lack activity against B2 and B3 enzymes. These findings indicate that cyclic boronate scaffolds have the potential to inhibit the full range of β-lactamases and justify further work on the development of boronates as broad-spectrum β-lactamase inhibitors

Sistema de seguridad para un laboratorío

En este proyecto se ha diseñado una aplicación que permite tener un sistema de seguridad que aplica exclusivamente visión computarizada y se comunica vía ETHERNET. Para este fin se ha empleado el paquete IMAQ Vision del software Labview 8.5 que nos permite adquirir imágenes de las credenciales para extraer así el número de matrícula de la persona a ser validada. Para ello es necesario utilizar una imagen patrón o plantilla que nos ayudará a buscar el área de interés, en nuestro caso el código de barras.En este proyecto se ha diseñado una aplicación que permite tener un sistema de seguridad que aplica exclusivamente visión computarizada y se comunica vía ETHERNET. Para este fin se ha empleado el paquete IMAQ Vision del software Labview 8.5 que nos permite adquirir imágenes de las credenciales para extraer así el número de matrícula de la persona a ser validada. Para ello es necesario utilizar una imagen patrón o plantilla que nos ayudará a buscar el área de interés, en nuestro caso el código de barras

Antibody isotypes, including IgG subclasses, in Ecuadorian patients with pulmonary paragonimiasis.

An ELISA test was developed to detect Paragonimus-specific antibodies, including IgG subclasses, using P. mexicanus crude water-soluble antigens. The test was standardized to detect antibodies in sera of Ecuadorian patients with pulmonary paragonimiasis and negative controls from the endemic area. The detected mean levels of IgG (0.753, SEM: 0.074) and IgM (0.303, SEM: 0.033) were significantly elevated (P < 0.05). Within the IgG subclasses, IgG4 showed the highest detected mean level (0.365, SEM: 0.116) and the other three subclasses showed considerably lower mean levels (IgG1, 0.186 SEM: 0.06; IgG2, 0.046 SEM: 0.01; IgG3, 0.123 SEM: 0.047). The number of P. mexicanus eggs found in sputum of infected individuals showed a positive correlation with the level of antibodies detected for IgM, IgG and its subclasses (P < 0.001). The relevance of these findings in Ecuadorian patients suffering from pulmonary paragonimiasis is discussed.Journal Articleinfo:eu-repo/semantics/publishe

WIPO Re:Search—A Platform for Product-Centered Cross-Sector Partnerships for the Elimination of Schistosomiasis

Schistosomiasis is an acute and chronic disease that affects over 200 million people worldwide, and with over 700 million people estimated to be at risk of contracting this disease, it is a pressing issue in global health. However, research and development (R&amp;D) to develop new approaches to preventing, diagnosing, and treating schistosomiasis has been relatively limited. Praziquantel, a drug developed in the 1970s, is the only agent used in schistosomiasis mass drug administration (MDA) campaigns, indicating a critical need for a diversified therapeutic pipeline. Further, gaps in the vaccine and diagnostic pipelines demonstrate a need for early-stage innovation in all areas of schistosomiasis product R&amp;D. As a platform for public-private partnerships (PPPs), the WIPO Re:Search consortium engages the private sector in early-stage R&amp;D for neglected diseases by forging mutually beneficial collaborations and facilitating the sharing of intellectual property (IP) assets between the for-profit and academic/non-profit sectors. The Consortium connects people, resources, and ideas to fill gaps in neglected disease product development pipelines by leveraging the strengths of these two sectors. Using WIPO Re:Search as an example, this article highlights the opportunities for the PPP model to play a key role in the elimination of schistosomiasis