Biology subjects

Gonzalez, G. M.

Publications and source records attributed to Gonzalez, G. M..

6 recordsLinked to original sources

bioRxiv2025

Antifungal susceptibility profile of clinically relevant species of the genus Sporothrix: establishment of Epidemiological Cutoff Values (ECVs) according to CLSI broth microdilution methodology

Sporotrichosis is a globally distributed subcutaneous mycosis caused mainly by Sporothrix brasiliensis, S. schenckii, and S. globosa. Cat-transmitted sporotrichosis, primarily caused by S. brasiliensis in South America and to a lesser extent by S. schenckii in Southeast Asia, is emerging as a significant public health concern, due its outbreak potential. Itraconazole is the first-choice drug for treatment of human and cats, but reduced susceptibility has been reported based on previously proposed epidemiological cut-off values (ECVs). To support resistance surveillance, we aimed to establish CLSI-endorsed ECVs for these clinically relevant Sporothrix species. A total of 3,588 minimum inhibitory concentration (MIC) values for seven antifungal agents (amphotericin B, itraconazole, posaconazole, voriconazole, isavuconazole, olorofim, and terbinafine) were obtained from 19 international laboratories. Four of seven antifungals met the CLSI M57 guidelines criteria to determine the ECV. Established ECVs for amphotericin B were found to be high with 8 {micro}g/mL for S. brasiliensis and S. globosa, and 4 {micro}g/mL for S. schenckii. Itraconazole ECVs were 4 {micro}g/mL for S. brasiliensis and S. schenckii. Posaconazole ECVs were 4 {micro}g/mL for all three species (tentative for S. globosa), while the terbinafine ECV for S. brasiliensis was 0.12 {micro}g/mL. Olorofim demonstrated good in vitro activity, particularly against S. brasiliensis. Overall, this study establishes validated ECVs for key antifungals against Sporothrix species and identifies a low prevalence of non-wild type (NWT) isolates, supporting ongoing antifungal resistance monitoring.

microbiology↗

bioRxiv2025

Enduring Autism-like Phenotypes and Deregulated Hypothalamic Prosocial Peptides After Early-Life Exposure to Indoor Flame Retardants in Male C57BL/6 Mice

BackgroundPolybrominated diphenyl ethers (PBDEs) are neuroendocrine disrupting chemicals that produce adverse neurodevelopmental effects. PBDEs have been implicated as risk factors for autism spectrum disorder (ASD), which is characterized by abnormal psychosocial functioning and is commonly accompanied by co-morbidities such as cognitive and attentional deficits. Here, we used a mouse model with translationally relevant exposure to establish direct causal evidence that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in male offspring. MethodsC57Bl6/N mouse dams were exposed to a commercial PBDE mixture, DE-71, via oral administration of 0 (vehicle control, VEH/CON), 0.1 (L-DE-71), or 0.4 (H-DE-71) mg/kg bw/d for 10 weeks, spanning three weeks prior to gestation through the end of lactation at postnatal day (PND) 21. ResultsMass spectrometric analysis indicated dose-dependent transfer of PBDEs (in ppb) to brains of F1 male offspring at PND 30, with reduction in levels by PND 110. Adult F1 male offspring displayed ASD-relevant neurobehavioral phenotypes, including impaired short- and long-term social recognition memory (SRM), despite intact general sociability, and exaggerated repetitive behavior. Exposed mice also displayed altered olfactory discrimination of social odors, impaired novel object recognition memory, and reduced open field habituation. However, no changes were observed in anxiety-like, sensorimotor, or depressive-like behaviors relative to VEH/CON. At the molecular level, DE-71 exposed males displayed deregulated gene markers of prosocial neuropeptides. Oxt was upregulated in the paraventricular nucleus (PVN); Avp was upregulated in the PVN and bed nucleus of the stria terminalis (BNST) but downregulated in the lateral septum (LS); Avp1ar and Adcyap1 were upregulated in the BNST; and Adcyap1r1 was upregulated in the PVN, supraoptic nucleus (SON), and BNST. ConclusionsThese findings demonstrate that developmental PBDE exposure produces enduring behavioral and neurochemical phenotypes that resemble core domains of ASD, which may result from early neurodevelopmental reprogramming within central social and memory networks.

neuroscience↗

bioRxiv2024

Effect of curcumin and 5-bromoindole-3-carboxyaldehyde on the inhibition of Quorum sensig-dependent virulence factors in Pseudomonas aeruginosa

Curcumin and 5-bromoindole-3-carboxaldehyde were tested for their ability to inhibit quorum sensing-dependent virulence factors in Pseudomonas aeruginosa strains Pa01, Pa14, and ATCC 27853. The compounds were evaluated at curcumin (1, 5 g/ml) and 5-bromoindole-3-carboxaldehyde (30, 50, 100 g/ml). Virulence factors--exoprotease, elastase, pyocyanin, and alginate --were measured. Chemoinformatics properties were analyzed using Molinspiration, Molsoft, Osiris Property Explorer, pkCSM, and SwissADME. Results showed 5-bromoindole-3-carboxaldehyde significantly reduced pyocyanin in Pa01 (92.5% at 100 g/ml), elastase (79.85% at 100 g/ml), exoprotease (92.8% at 50 g/ml), and alginate in ATCC 27853 (76.16% at 100 g/ml). Curcumin effectively inhibited pyocyanin in ATCC 27853 (100% at 5 g/ml), elastase in Pa14 (56.19% at 5 g/ml), exoprotease in Pa01 (87.04% at 5 g/ml), and alginate (48.26% at 5 g/ml). Both compounds demonstrated strong inhibition of virulence factors, suggesting their potential as anti-virulence agents against P. aeruginosa, a highly resistant bacterium prevalent in nosocomial infections.

microbiology↗

bioRxiv2023

Evaluation of antimicrobial activity of Kefir drink against Escherichia coli, Salmonella typhimurium and Shigella flexneri.

ObjectiveEvaluate the antimicrobial activity of the Kefir drink against Escherichia coli, Salmonella typhimurium and Shigella flexneri MethodThe Kefir used in the investigation was acquired in Toluca, State of Mexico. We performed a reactivation of Kefir with pasteurized milk and analyzed 3 carbohydrates (honey, sugar and piloncillo) at different concentrations and times, 80, 100, 120% and 24, 48 and 72 hours respectively. Isolated cultivable microorganisms were characterized by phenotypic, biochemical and mass spectroscopy techniques. The initial and final pH were determined during the study time. The antimicrobial activity was carried out by extracting the metabolites present in the ferment with the Kirby-Bauer method, in addition the direct ferment was evaluated, to determine if there was inhibition with the Escherichia coli (ATCC 11229) strains, Salmonella typhimurium (ATCC 14028) and Shigella flexneri (ATCC 12022). ResultsIt was observed that in the three carbohydrates used at a concentration of 120% and at a time of 72 h, a lower pH was obtained (3.51 to 3.64) compared to their initial concentration (6.50 to 6.64). From the metabolites extracted in the different ferments, no inhibition halo was obtained with the strains analyzed. However, when using direct ferments, it was observed that in the carbohydrates used (sugar, honey, piloncillo) there was the presence of an inhibiting halo or the growth of colonies other than those evaluated. The isolated cultivable microorganisms were: Pichia kudriavzevii (yeast); Enterococcus sp (gram-positive coconut) and Lactobacillus sp (gram-positive bacillus). ConclusionsKefir ferments made with different carbohydrates, came to present a degree of inhibition only as a consortium against Gram-negative microorganisms analyzed.

microbiology↗

bioRxiv2021

Persistent autism-relevant phenotype produced by in utero and lactational exposure of female mice to the commercial PBDE mixture, DE-71

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display altered short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.

neuroscience↗

bioRxiv2020

Maternal Transfer of Environmentally Relevant Polybrominated Diphenyl Ethers (PBDEs) Produces a Diabetic Phenotype and Disrupts Glucoregulatory Hormones and Hepatic Endocannabinoids in Adult Mouse Female Offspring

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucose regulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses showed that DE-71 produced fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occur more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity, decreased thermogenic brown adipose tissue mass and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and -153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.

physiology↗