Differential expression of biomarkers in saliva related to SARS-CoV-2 infection in patients with mild, moderate and severe COVID-19.

BACKGROUND: Severe COVID-19 is a disease characterized by profound dysregulation of the innate immune system. There is a need to identify highly reliable prognostic biomarkers that can be rapidly assessed in body fluids for early identification of patients at higher risk for hospitalization and/or death. This study aimed to assess whether differential gene expression of immune response molecules and cellular enzymes, detected in saliva samples of COVID-19 patients, occurs according to disease severity staging. METHODS: In this cross-sectional study, subjects with a COVID-19 diagnosis were classified as having mild, moderate, or severe disease based on clinical features. Transcripts of genes encoding 6 biomarkers, IL-1ß, IL-6, IL-10, C-reactive protein, IDO1 and ACE2, were measured by RT‒qPCR in saliva samples of patients and COVID-19-free individuals. RESULTS: The gene expression levels of all 6 biomarkers in saliva were significantly increased in severe disease patients compared to mild/moderate disease patients and healthy controls. A significant strong inverse relationship between oxemia and the level of expression of the 6 biomarkers (Spearman's correlation coefficient between -0.692 and -0.757; p < 0.001) was found. CONCLUSIONS: Biomarker gene expression determined in saliva samples still needs to be validated as a potentially valuable predictor of severe clinical outcomes early at the onset of COVID-19 symptoms.

Metallo-beta-lactamase-producing Escherichia coli in the sewage of Mexico City: where do they come from?

While monitoring the presence of antibiotic resistance in municipal wastewater bacteria from Mexico City, five Escherichia coli isolates were found to be resistant to carbapenems, antibiotics of "last resort" used mostly in hospitals. Further analysis revealed that these carbapenem-resistant isolates carried the gene encoding a metallo-beta-lactamase, NDM-5. The gene was found to be beared by a large, ∼145 kb conjugative plasmid, which also carries putative genes encoding resistance to sulfonamides, trimethoprim, tetracycline, ciprofloxacin, and chloramphenicol (although no phenotypic chloramphenicol resistance was detected) and quaternary-ammonium compounds. The plasmid also carried gene mobility determinants, such as integron integrase and two transposases. In addition to the direct public health threat posed by the presence of such multi-resistant organisms in wastewater released into the environment and used for crop irrigation; it is particularly concerning that carbapenem-resistant E. coli is rather rare in Mexican hospitals (<1%), but was found in small, 100 mL samples of municipal wastewater. This suggests that these organisms are under-reported by clinical microbiology laboratories, underlining the usefulness of wastewater monitoring, or that there is an unknown source of such carbapenem-resistant organisms that are being dumped into the wastewater. The source of these bacteria must be assessed and controlled to prevent further spread of this multi-resistance plasmid among other environmental and clinical microorganisms.

RNA Microarray-Based Comparison of Innate Immune Phenotypes between Human THP-1 Macrophages Stimulated with Two BCG Strains.

Currently, the only available vaccine against tuberculosis is Mycobacterium bovis Bacille Calmette-Guérin (BCG). Pulmonary tuberculosis protection provided by the vaccine varies depending on the strain, the patient's age and the evaluated population. Although the adaptive immune responses induced by different BCG strains have been widely studied, little conclusive data is available regarding innate immune responses, especially in macrophages. Here, we aimed to characterize the innate immune responses of human THP-1-derived macrophages at the transcriptional level following a challenge with either the BCG Mexico (M.BCG) or Phipps (P.BCG) strains. After a brief in vitro characterization of the bacterial strains and the innate immune responses, including nitric oxide production and cytokine profiles, we analyzed the mRNA expression patterns and performed pathway enrichment analysis using RNA microarrays. Our results showed that multiple biological processes were enriched, especially those associated with innate inflammatory and antimicrobial responses, including tumor necrosis factor (TNF)-α, type I interferon (IFN-I) and IFN-γ. However, four DEGs were identified in macrophages infected with M.BCG compared to P. BCG. These findings indicated the proinflammatory stimulation of macrophages induced by both BCG strains, at the cytokine level and in terms of gene expression, suggesting a differential expression pattern of innate immune transcripts depending on the mycobacterial strain.

The Cysteine Protease Giardipain-1 from Giardia duodenalis Contributes to a Disruption of Intestinal Homeostasis.

In giardiasis, diarrhoea, dehydration, malabsorption, weight loss and/or chronic inflammation are indicative of epithelial barrier dysfunction. However, the pathogenesis of giardiasis is still enigmatic in many aspects. Here, we show evidence that a cysteine protease of Giardia duodenalis called giardipain-1, contributes to the pathogenesis of giardiasis induced by trophozoites of the WB strain. In an experimental system, we demonstrate that purified giardipain-1 induces apoptosis and extrusion of epithelial cells at the tips of the villi in infected jirds (Meriones unguiculatus). Moreover, jird infection with trophozoites expressing giardipain-1 resulted in intestinal epithelial damage, cellular infiltration, crypt hyperplasia, goblet cell hypertrophy and oedema. Pathological alterations were more pronounced when jirds were infected intragastrically with Giardia trophozoites that stably overexpress giardipain-1. Furthermore, Giardia colonization in jirds results in a chronic inflammation that could relate to the dysbiosis triggered by the protist. Taken together, these results reveal that giardipain-1 plays a key role in the pathogenesis of giardiasis.

Non-tuberculous mycobacteria immunopathogenesis: Closer than they appear. a prime of innate immunity trade-off and NTM ways into virulence.

INTRODUCTION: The growing incidence of non-tuberculous mycobacteria (NTM) and changes in epidemiological factors have indicated that immune dysregulation may be associated with the emergence of NTM. Minireview entails to acknowledge complex interaction and new ways NTM are evolving around diverse immune status. METHODS: In order to perform this review, we selected peer reviewed, NLM database articles under the terms NTM, mycobacterium complex 'AND' -Host- immune response, immunity regulation, Disease, Single Nucleotide Polymorphism (SNP´s), and -pathogen- followed by a snow ball rolling basis search on immune components and NTM related with diseases distribution. RESULTS: The universal exposure and diversity of NTM are well-documented; however, hospitals seldom establish vigilant control of water quality or immunodeficiencies for patients with NTM infections. Depending on the chemical structures and immune mechanisms presented by various NTM varieties, they can trigger different effects in dendritic and natural killer cells, which release interleukin (IL)-17, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and rIL-1B. The T helper (Th)2-acquired immune response is responsible for autoimmune responses in patients with NTM infections, and, quite disturbingly, immunocompetent patients have been reported to suffer from NTM infections. CONCLUSION: New technologies and a comprehensive view has taught us; to acknowledge metabolic/immune determinants and trade-offs along transit through mutualism-parasite continuous.

More fuel to the fire: some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa.

BACKGROUND: In contrast to the well-characterized Celiac Disease (CD), the clinical scenarios encompassed by the non-celiac self-reported wheat sensitivity (NCSRWS) might be related to different antigens that trigger distinct immune-inflammatory reactions. Although an increased number of intestinal intraepithelial lymphocytes is observed at the inception of both diseases, the subsequent immunopathogenic pathways seem to be different. We aimed to describe the cytokine profile observed in the duodenal mucosa of patients with NCSRWS. METHODS: In a blind, cross-sectional study, we included duodenal biopsies from 15 consecutive untreated patients with active CD, 9 individuals with NCSRWS and 10 subjects with dyspepsia without CD and food intolerances. Immunohistochemistry and flow-cytometry were used to determine the presence of pro-inflammatory cytokine expressing monocytes and monocyte-derived dendritic cells involved in innate immune activation, cytokine-driven polarization and maintenance of Th1 and Th17/Th 22, and anti-inflammatory/profibrogenic cytokines. RESULTS: The percentage of cells expressing all tested cytokines in the lamina propria and the epithelium was higher in CD patients than in the control group. Cytokines that induce and maintain Th1 and Th17 polarization were higher in CD than in NCSRWS and controls, also were higher in NCSRWS compared to controls. Similar differences were detected in the expression of IL-4 and TGF-1, while IL-10-expressing cells were lower in NCSRWS patients than in controls and CD subjects. CONCLUSIONS: NCSRWS patients exhibit components of both, innate and adaptive immune mechanisms but to a lesser extent compared to CD.

Antimicrobial resistance and antibiotic consumption in Mexican hospitals.

OBJECTIVE: To establish the current situation of antimicrobial resistance and antibiotic consumption in Mexican hospitals. MATERIALS AND METHODS: Antimicrobial susceptibility data from blood and urine isolates were collected. Defined daily dose (DDD) of antibiotic consumption/100 occupied beds (OBD) was calculated. RESULTS: Study period: 2016 and 2017. Of 4 382 blood isolates, E. coli and K. pneumoniae were most frequently reported, with antimicrobial resistance >30% for most drugs tested, only for carbapenems and amikacin resistance were <20%. A. baumannii had antimicrobial resistance >20% to all drugs. Resistance to oxacillin in S. aureus was 20%. From 12 151 urine isolates, 90% corresponded to E. coli; resistance to ciprofloxacin, cephalosporins and trimethoprim/sulfamethoxazole was >50%, with good susceptibility to nitrofurantoin, amikacin and carbapenems. Global median antimicrobial consumption was 57.2 DDD/100 OB. CONCLUSIONS: s. This report shows a high antimicrobial resistance level in Gram-negative bacilli and provides an insight into the seriousness of the problem of antibiotic consumption.

OBJETIVO: Establecer la situación actual de la resistencia antimicrobiana y el consumo de antibióticos en hospitales mexicanos. MATERIAL Y MÉTODOS: Se colectaron datos de susceptibilidad antimicrobiana de aislamientos de sangre y orina. Se calculó la dosis diaria definida (DDD) del consumo de antibióticos/100 estancias. RESULTADOS: Periodo de estudio de 2016 a 2017. De 4 382 aislamientos en sangre, E. coli y K. pneumoniae fueron las más frecuentes, con resistencia >30% a la mayoría de las drogas evaluadas; sólo para carbapenémicos y amikacina la resistencia fue <20%. A. baumannii tuvo resistencia >20% a todos los fármacos. La resistencia a oxacilina en S. aureus fue de 20%. De 12 151 aislamientos en urocultivos, 90% correspondió a E. coli; la resistencia a ciprofloxacina, cefalosporinas y trimetoprima/sulfametoxazol fue >50%, con buena susceptibilidad a nitrofurantoína, amikacina y carbapenémicos. La mediana del consumo global de antibióticos en DDD/100 estancias fue de 57.2. CONCLUSIONES: Este reporte muestra el nivel elevado de resistencia en bacilos Gram-negativos y brinda una perspectiva de la gravedad del problema del consumo de antibióticos.

Recombinant O-mannosylated protein production (PstS-1) from Mycobacterium tuberculosis in Pichia pastoris (Komagataella phaffii) as a tool to study tuberculosis infection.

BACKGROUND: Pichia pastoris (syn. Komagataella phaffii) is one of the most highly utilized eukaryotic expression systems for the production of heterologous glycoproteins, being able to perform both N- and O-mannosylation. In this study, we present the expression in P. pastoris of an O-mannosylated recombinant version of the 38 kDa glycolipoprotein PstS-1 from Mycobacterium tuberculosis (Mtb), that is similar in primary structure to the native secreted protein. RESULTS: The recombinant PstS-1 (rPstS-1) was produced without the native lipidation signal. Glycoprotein expression was under the control of the methanol-inducible promoter pAOX1, with secretion being directed by the α-mating factor secretion signal. Production of rPstS-1 was carried out in baffled shake flasks (BSFs) and controlled bioreactors. A production up to ~ 46 mg/L of the recombinant protein was achieved in both the BSFs and the bioreactors. The recombinant protein was recovered from the supernatant and purified in three steps, achieving a preparation with 98% electrophoretic purity. The primary and secondary structures of the recombinant protein were characterized, as well as its O-mannosylation pattern. Furthermore, a cross-reactivity analysis using serum antibodies from patients with active tuberculosis demonstrated recognition of the recombinant glycoprotein, indirectly indicating the similarity between the recombinant PstS-1 and the native protein from Mtb. CONCLUSIONS: rPstS-1 (98.9% sequence identity, O-mannosylated, and without tags) was produced and secreted by P. pastoris, demonstrating that this yeast is a useful cell factory that could also be used to produce other glycosylated Mtb antigens. The rPstS-1 could be used as a tool for studying the role of this molecule during Mtb infection, and to develop and improve vaccines or kits based on the recombinant protein for serodiagnosis.

[Diagnóstico tardío de psoriasis: motivos y consecuencias]. / Late diagnosis of psoriasis: Reasons and consequences.

BACKGROUND: Psoriasis is an autoimmune skin disease that may be associated with articular manifestations, and the most common clinical presentation is the variety "in plaques". In Mexico, in the Centro Dermatológico Pascua, it is the eighth leading cause of consultation. The aim of this study was to determine the diagnostic process of patients in a reference center for diseases of the skin. METHODS: Performing an analytical cross-sectional study that included 100 patients where the diagnostic process was questioned, clinimetric scales were applied and evaluated anthropometric. RESULTS: It was found that 70% of patients had taken over a month to get medical care (median: 3 months; IQR: 11 months), having consulted in 61% to a general physician as a doctor of first contact and 89% being diagnosed by a dermatologist. Eighty-eight percent of the patients were overweight or obese. We found as a factor of delay, a partnership with the variable of having an Institutional Medical Service (p = 0.019; U = 695.5). CONCLUSION: it is necessary to design a system to shorten the diagnostic process, not only in psoriasis, in addition to emphasizing dermatological education.

[Resistance to antibiotic: A serious global problem]. / La resistencia a los antibióticos: Un grave problema global.

An important piece of improvement in public health standards, medicine achievements, and development is based on the impressive effect of vaccines and antibiotics on infectious diseases. However, the last three or so decades have witnessed how an unsound use of antibiotics has resulted in antibiotic multi-resistant clones in hospitals and community environments. It also has been said that antibiotic research and the development pipeline has crashed, leading to no new antibiotic molecules to be tested at a time of treatment failure, manifest with unacceptable frequency as an increased economic and human cost in lives. Like the name of the series, antibiotic resistance is a global problem with clear evolutionary roots and a broad local impact. In that sense, this review explores the interaction among resistant mechanisms, underlying motives of expansion and actual trends in antibiotic resistance upgrade to limit the problem. Conceivably, only the involvement of players at every level, and coordinated actions accordingly constitute the necessary elements for effectively intervention.

The detection of inherent homologous recombination between repeat sequences in H. pylori 26695 by the PCR-based method.

Helicobacter pylori infects more than half of the world's population, making it the most widespread infection of bacteria. It has high genetic diversity and has been considered as one of the most variable bacterial species. In the present study, a PCR-based method was used to detect the presence and the relative frequency of homologous recombination between repeat sequences (>500 bp) in H. pylori 26695. All the recombinant structures have been confirmed by sequencing. The inversion generated between inverted repeats showed distinct features from the recombination for duplication or deletion between direct repeats. Meanwhile, we gave the mathematic reasoning of a general formula for the calculation of relative recombination frequency and indicated the conditions for its application. This formula could be extensively applied to detect the frequency of homologous recombination, site-specific recombination, and other types of predictable recombination. Our results should be helpful for better understanding the genome evolution and adaptation of bacteria.

Catecholamine norepinephrine diminishes lung epithelial cell adhesion of Streptococcus pneumoniae by binding iron.

Systemic release of norepinephrine (NE) is a component of the acute host response to infection, and studies in the field of microbial endocrinology indicate generally that NE increases the bacterial growth rate and promotes invasive disease. However, NE attenuates experimental invasive pneumococcal disease. We determined that NE promoted pneumococcal growth but paradoxically decreased pneumococcal adhesion to host cells. This effect was independent of the classical adhesin CbpA. Microarray analysis indicated that the effect of NE involved two two-component regulatory systems that both regulate expression of the Piu iron uptake ABC transport operon. We propose that NE, a known siderophore, enhances iron availability to the bacteria, resulting in greater bacterial replication and decreased expression of Piu operon products. Downregulation of the operon includes decreased expression of the Piu-associated adhesin PiuD. Our results suggested that the iron-dependent inhibitory effect of NE on pneumococcal adherence is a mechanism underlying the amelioration of pneumococcal disease by NE.

Identification of peptides presented through the MHC-II of dendritic cells stimulated with Mycobacterium avium.

Mycobacterium avium (M. avium) represents a species of concern, because of its ability to modulate the host's innate immune response, and therefore influence trajectory of adaptative immunity. Since eradicative response against mycobacteria, and M. tuberculosis/M. avium, relies on peptides actively presented on a Major Histocompatibility complex-II (MHC-II) context, we assessed paradoxical stimulation of Dendritic Cell resulting on immature immunophenotype characterized by membrane minor increase of MHC-II and CD40 despite of high expression of the pro-inflammatory tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in supernatants. Identification of M. avium leucine rich peptides forming short α-helices shutting down Type 1T helper (Th1), contribute to the understanding of immune evasion of an increasingly prevalent pathogen, and may provide a basis for future immunotherapy to infectious and non-infectious disease.

Removal of bacterial pathogens and antibiotic resistance bacteria by anaerobic sludge digestion with thermal hydrolysis pre-treatment and alkaline stabilization post-treatment.

Primary sludge (PS) is associated with public health and environmental risks, so regulations focus on reducing the pathogenic and heavy metal contents of the treated material (biosolids), intended for soil amendments and land reclamation. The regulations set limits for Escherichia coli (or fecal coliforms), Salmonella spp., helminth eggs and enterovirus. However, the potential risk due to antibiotic resistant bacteria (ARB) and other human potential pathogenic bacteria (HPB) are not considered. In this work, three sludge treatment processes, having in common an anaerobic digestion step, were applied to assess the removal of regulated bacteria (fecal coliforms, Salmonella spp), ARB and HPB. The treatment arrangements, fed with PS from a full-scale wastewater treatment plant were: 1) Mesophilic anaerobic digestion followed by alkaline stabilization post-treatment (MAD-CaO); 2) Thermophilic anaerobic digestion (TAD) and, 3) Pre-treatment (mild thermo-hydrolysis) followed by TAD (PT-TAD). The results address the identification, quantification (colony forming units) and taxonomic characterization of ARB resistant to ß-lactams and vancomycin, as well as the taxonomic characterization of HPB by sequencing with PacBio. In addition, quantification based on culture media of fecal coliforms and Salmonella spp. is presented. The capabilities and limitations of microbiological and metataxonomomic analyses based on PacBio sequencing are discussed, emphasizing that they complement each other. Genus Aeromonas, Acinetobacter, Citrobacter, Enterobacter, Escherichia, Klebsiella, Ochrobactrum, Pseudomonas and Raoultella, among others, were found in the PS, which are of clinical or environmental importance, being either HPB, HPB-ARB, or non-pathogenic ARB with the potentiality of horizontal gene transfer. Based on the analysis of fecal coliforms and Salmonella spp., the three processes produced class A (highest) biosolids, suitable for unrestricted agriculture applications. Mild thermo-hydrolisis was effective in decreasing ARB cultivability, but it reappeared after the following TAD. O. intermedium (HPB-ARB) was enriched in MAD and TAD while Laribacter hongkongensis (HPB) did persist after the applied treatments.

Comparative characterization of inflammatory profile and oral microbiome according to an inflammation-based risk score in ST-segment elevation myocardial infarction.

Ischemic heart disease considers the myocardial infarction (MI), either non-ST-segment elevation (non-STEMI) or ST-segment elevation myocardial infarction (STEMI); this represents the main cause of mortality in Mexican population. Regarding to the inflammatory state, this is reported to be a major prognostic factor of mortality for patients with MI. One of the conditions capable of producing systemic inflammation is periodontal disease. It has been proposed that the oral microbiota is translocated through the bloodstream to the liver and intestine, generating intestinal dysbiosis. The aim of this protocol is to assess oral microbiota diversity and circulating inflammatory profile in STEMI patients stratified according to an inflammation-based risk scoring system. We found that Bacteriodetes phylum was the most abundant in STEMI patients, and Prevotella was the most abundant genus, with a higher proportion in periodontitis patients. In fact, Prevotella genus was found to correlate positively and significantly with elevated IL-6 concentration. Our study defined a non-causal association inferred between the cardiovascular risk of STEMI patients, determined by changes in the oral microbiota that influence the development of periodontal disease and its relationship with the exacerbation of the systemic inflammatory response.

Removal of intI1, ARGs, and SARS-CoV-2 and changes in bacterial communities in four sewage treatment facilities.

Currently, discharge regulations for wastewater treatment plants (WWTPs) are based on conventional parameters, but more is needed to ensure safe water reuse. In particular, emerging pollutants, as antimicrobials and antibiotic resistance genes (ARGs), are not considered. This research focuses on the fate of emerging biological contaminants during wastewater treatment in Mexico City. intI1 and the ARGs cphA-02, OXA-10 and sul1 were analyzed by qPCR; pathogenic bacteria species were characterized by high throughput sequencing of complete 16S rRNA gene, and fragments of SARS-CoV-2 were quantified by RT-qPCR. Conventional parameters (chemical oxygen demand and coliform bacteria) were also determined. Two sampling campaigns (rainy and dry seasons) were carried out in four municipal WWTPs in Mexico City, representing five biological treatment processes: conventional activated sludge, extended aeration activated sludge, membrane bioreactor, direct anaerobic digestion, and constructed wetland, followed by ultraviolet light or chlorine disinfection. In most cases, gene fragments of SARS-CoV-2 were eliminated below the detection limit of RT-qPCR. The abundance of intI1 positively correlated with the sul1, OXA-10, and cphA-02 abundances; intI1 and the ARGs here studied were partially removed in the WWTPs, and in most cases, the number of copies per second discarded in the sludge were higher those in the effluent. The treatment processes decreased the abundance of dominant bacterial groups in the raw wastewater, while enriching bacterial groups in the effluent and the biological sludge, with possible pollutant removal capabilities. Bacterial communities in the raw wastewater showed the predominance of the genus Arcobacter (from 62.4 to 86.0 %) containing potentially pathogenic species. Additionally, DNA of some species persisted after the treatment processes: A. johnsonii, A. junii, A. caviae, A. hydrophila, A. veronii, A. butzleri, A. cryaerophilus, Chryseobacterium indologenes, Hafnia paralvei, M. osloensis, Pseudomonas putida and Vibrio cholerae, which deserves special attention in future regulation for safe water reuse.

The Real Practice Prescribing Antibiotics in Outpatients: A Failed Control Case Assessed through the Simulated Patient Method.

The first level of medical care provides the largest number of consultations for the most frequent diseases at the community level, including acute pharyngitis (AP), acute diarrhoea (AD) and uncomplicated acute urinary tract infections (UAUTIs). The inappropriate use of antibiotics in these diseases represents a high risk for the generation of antimicrobial resistance (AMR) in bacteria causing community infections. To evaluate the patterns of medical prescription for these diseases in medical offices adjacent to pharmacies, we used an adult simulated patient (SP) method representing the three diseases, AP, AD and UAUTI. Each person played a role in one of the three diseases, with the signs and symptoms described in the national clinical practice guidelines (CPGs). Diagnostic accuracy and therapeutic management were assessed. Information from 280 consultations in the Mexico City area was obtained. For the 101 AP consultations, in 90 cases (89.1%), one or more antibiotics or antivirals were prescribed; for the 127 AD, in 104 cases (81.8%), one or more antiparasitic drugs or intestinal antiseptics were prescribed; for the scenarios involving UAUTIs in adult women, in 51 of 52 cases (98.1%) one antibiotic was prescribed. The antibiotic group with the highest prescription pattern for AP, AD and UAUTIs was aminopenicillins and benzylpenicillins [27/90 (30%)], co-trimoxazole [35/104 (27.6%)] and quinolones [38/51 (73.1%)], respectively. Our findings reveal the highly inappropriate use of antibiotics for AP and AD in a sector of the first level of health care, which could be a widespread phenomenon at the regional and national level and highlights the urgent need to update antibiotic prescriptions for UAUTIs according to local resistance patterns. Supervision of adherence to the CPGs is needed, as well as raising awareness about the rational use of antibiotics and the threat posed by AMR at the first level of care.

Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico.

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

Limited Therapeutic Options in Mexico for the Treatment of Urinary Tract Infections.

The rise in antimicrobial resistance (AMR) has complicated the management of urinary tract infections (UTIs). The objective of this study was to evaluate the antimicrobial susceptibility patterns of Escherichia coli and Klebsiella pneumoniae. Design: prospective observational study. Bacteria were classified as susceptible or resistant to ampicillin-sulbactam, amikacin, gentamicin, ciprofloxacin, norfloxacin, nitrofurantoin, trimethoprim-sulfamethoxazole (TMP/SMZ), ertapenem, meropenem, and fosfomycin. The sensitivity to fosfomycin and chloramphenicol was evaluated by the disk diffusion method. Statistical analysis: the chi-square test and Fisher's exact test were used to compare differences between categories. A p value < 0.05 was considered statistically significant. Isolates were collected from January 2019 to November 2020 from 21 hospitals and laboratories. A total of 238 isolates were received: a total of 156 E. coli isolates and 82 K. pneumoniae isolates. The majority were community-acquired infections (64.1%). Resistance was >20% for beta-lactams, aminoglycosides, fluoroquinolones, and TMP/SMZ. For E. coli isolates, resistance was <20% for amikacin, fosfomycin, and nitrofurantoin; for K. pneumoniae, amikacin, fosfomycin, chloramphenicol, and norfloxacin. All were susceptible to carbapenems. K. pneumoniae isolates registered a higher proportion of extensively drug-resistant bacteria in comparison with E. coli (p = 0.0004). In total, multidrug-resistant bacteria represented 61% of all isolates. Isolates demonstrated high resistance to beta-lactams, fluoro-quinolones, and TMP/SMZ.

Proteome Profile Changes Induced by Heterologous Overexpression of Mycobacterium tuberculosis-Derived Antigens PstS-1 (Rv0934) and Ag85B (Rv1886c) in Mycobacterium microti.

The development of new tuberculosis vaccines remains a global priority, and recombinant vaccines are a frequently investigated option. These vaccines follow a molecular strategy that may enhance protective efficacy. However, their functional differences, particularly with respect to glycosylation, remain unknown. Recent studies have shown that glycosylation plays a key role in the host-pathogen interactions during immune recognition. The aim of this study was to determine the differences in the glycosylation profiles of two recombinant strains of Mycobacterium microti, overexpressing Ag85B (Rv1886c) and PstS-1 (Rv0934) antigens of M. tuberculosis. For each strain, the glycosylation profile was determined by Western blotting with lectins. The results showed the presence of mannosylated proteins and evidence of linked sialic acid proteins. Interestingly, different proteome and glycoproteome profiles were observed between the two recombinant strains and the wild-type strain. We have shown here that the construction of the recombinant strains of M. microti has altered the proteome and glycosylation profiles of these strains, leading us to ask what impact these changes might have on the immune response.