Resistance to fosfomycin is increasing and is significantly associated with extended-spectrum β-lactamase-production in urinary isolates of Escherichia coli

Fosfomycin has become a therapeutic option in urinary tract infections. Our objective was to evaluate the in vitro activity of fosfomycin against Escherichia coli isolated from urine samples in 2013, 2018 and 2021. We also determined a putative association between fosfomycin resistance and extended-spectrum β-lactamases (ESBL) production. Fosfomycin activity was evaluated against 7367, 8128 and 5072 Escherichia coli urinary isolates in 2013, 2018 and 2021, respectively. We compare the prevalence of fosfomycin-resistant strains among the ESBL- and non-ESBL-producing isolates. MICs of fosfomycin, cefotaxime, and cefotaxime-clavulanate were determined by a microdilution method. 302 ESBL-producers were selected to determine MICs of fosfomycin by agar dilution and genes encoding ESBLs were detected by PCR. Among the total of ESBL-producing strains, 14.3%, 20.8% and 20% were resistant to fosfomycin in 2013, 2018 and 2021, respectively, whereas fosfomycin resistance in non-ESBL producers was 3.5%, 4.05% and 5.53% for each year (P ≤ 0.001). In the 302 selected ESBL-producing isolates, CTX-M was the main ESBL (228 isolates), being 50.7% CTX-M-15. Resistance to fosfomycin among these ESBL-producing strains was associated (P = 0.049) with isolates that produced the CTX-M type. Our data show that fosfomycin resistance is increasing in Escherichia coli urinary isolates and it is related to ESBL-production. A follow-up of fosfomycin resistance is required

Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain

In Western Europe, the HIV-1 epidemic among men who have sex with men (MSM) is dominated by subtype B. However, recently, other genetic forms have been reported to circulate in this population, as evidenced by their grouping in clusters predominantly comprising European individuals. Here we describe four large HIV-1 non-subtype B clusters spreading among MSM in Spain. Samples were collected in 9 regions. A pol fragment was amplified from plasma RNA or blood-extracted DNA. Phylogenetic analyses were performed via maximum likelihood, including database sequences of the same genetic forms as the identified clusters. Times and locations of the most recent common ancestors (MRCA) of clusters were estimated with a Bayesian method. Five large non-subtype B clusters associated with MSM were identified. The largest one, of F1 subtype, was reported previously. The other four were of CRF02_AG (CRF02_1; n = 115) and subtypes A1 (A1_1; n = 66), F1 (F1_3; n = 36), and C (C_7; n = 17). Most individuals belonging to them had been diagnosed of HIV-1 infection in the last 10 years. Each cluster comprised viruses from 3 to 8 Spanish regions and also comprised or was related to viruses from other countries: CRF02_1 comprised a Japanese subcluster and viruses from 8 other countries from Western Europe, Asia, and South America; A1_1 comprised viruses from Portugal, United Kingom, and United States, and was related to the A1 strain circulating in Greece, Albania and Cyprus; F1_3 was related to viruses from Romania; and C_7 comprised viruses from Portugal and was related to a virus from Mozambique. A subcluster within CRF02_1 was associated with heterosexual transmission. Near full-length genomes of each cluster were of uniform genetic form. Times of MRCAs of CRF02_1, A1_1, F1_3, and C_7 were estimated around 1986, 1989, 2013, and 1983, respectively. MRCA locations for CRF02_1 and A1_1 were uncertain (however initial expansions in Spain in Madrid and Vigo, respectively, were estimated) and were most probable in Bilbao, Spain, for F1_3 and Portugal for C_7. These results show that the HIV-1 epidemic among MSM in Spain is becoming increasingly diverse through the expansion of diverse non-subtype B clusters, comprising or related to viruses circulating in other countries

Resistencia a aminoglicósidos|bestudios bioquímicos y genéticos en el género "Staphylococcus"

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 29-11-199

ACE2 is on the X chromosome: could this explain COVID-19 gender differences?

This commentary refers to ‘Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors’, by I.E. Sama et al., 2020;41:1810–1817. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease termed coronavirus disease 2019 (COVID-19) shows a fatality rate greater in men compared with women.1 To explain this, some hypotheses have been raised, from genes that regulate the immune system encoded on the X chromosome to smoking behaviour,2 to expression levels1 or variants for angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2.3However, we would like to point out that the ACE2 gene is located on the X chromosome (location: Xp22.2; nucleotides 15 494 402–15 602 148, GRCh38.hg38 version). To our knowledge, the importance of ACE2 localization on the X chromosome has not been explored previously. Often, to have two copies ameliorates the deleterious effects of X-linked diseases and, as a consequence, most X-linked syndromes produce male diseases.Funded by Autonoma University and Hospital Clínico San Carlos (employer).Peer reviewe

Crystal structure of Hcp from Acinetobacter baumannii: a component of the type VI secretion system

16 p.-6 fig.-1 tab.The type VI secretion system (T6SS) is a bacterial macromolecular machine widely distributed in Gram-negative bacteria, which transports effector proteins into eukaryotic host cells or other bacteria. Membrane complexes and a central tubular structure, which resembles the tail of contractile bacteriophages, compose the T6SS. One of the proteins forming this tube is the hemolysin co-regulated protein (Hcp), which acts as virulence factor, as transporter of effectors and as a chaperone. In this study, we present the structure of Hcp from Acinetobacter baumannii, together with functional and oligomerization studies. The structure of this protein exhibits a tight β barrel formed by two β sheets and flanked at one side by a short α-helix. Six Hcp molecules associate to form a donut-shaped hexamer, as observed in both the crystal structure and solution. These results emphasize the importance of this oligomerization state in this family of proteins, despite the low similarity of sequence among them. The structure presented in this study is the first one for a protein forming part of a functional T6SS from A. baumannii. These results will help us to understand the mechanism and function of this secretion system in this opportunistic nosocomial pathogen.Peer reviewe

Analysis of Adverse Effects of COVID-19 Vaccines in Spain following Booster Dose

The present study evaluates the adverse effects of three vaccines: AstraZeneca (Vaxzevria), Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax) according to the dose. From 733 participants collected, the vaccine schedule was as follows: 330 (45%) received a double dose of the AstraZeneca vaccine, 382 (52.1%) received a double dose of Pfizer, 18 (2.5%) received a heterologous prime boost and 3 (0.4%) received a single dose. Pfizer and Moderna vaccines were administered as a third dose in 70 and 121 individuals, respectively. Local and systemic reactions observed in the three vaccines were mild to moderate in severity. Only one AstraZeneca recipient (0.3%) presented a serious adverse effect: blurred vision. Adverse events were more frequent after the first dose of AstraZeneca and after the second dose of Pfizer. As the third dose, Moderna causes more adverse effects than Pfizer regardless of the type of vaccine previously administered, whereas the reactogenicity of a third dose of Pfizer is slightly higher in the group previously vaccinated with Pfizer than in that group with AstraZeneca. In short, secondary effects of the third dose of COVID-19 vaccines were similar to those after dose 2, but their frequency depends on the type of vaccine and the combinations of vaccines

Transcriptional attenuation control of the tylosin‐resistance gene tlrA in Streptomyces fradiae

The tylosin producer Streptomyces fradiae contains four known resistance genes, two of which (tlrA and tlrD) encode methyltransferases that act on ribosomal RNA at a common site. Expression of tlrA is regulated via transcriptional attenuation. A short transcript, only 411 nucleotides long, terminates 27 nucleotides into the methylase‐coding sequence in the uninduced state. Induction of tlrA is proposed to involve a ribosome‐mediated conformational change within the mRNA leader that allows transcription to continue beyond the attenuation site, resulting in a transcript about 1450 nucleotides long. Transplantation of tlrD and/or tlrA into Streptomyces albus revealed that the induction specificity of tlrA depends upon the state of the ribosomes and is significantly altered in strains also expressing tlrD