Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

Significance and Impact of the Study: The continuous rise of antibiotic resistance in bacteria such as Pseudomonas aeruginosa is a serious threat to human health, hence it is mandatory to identify novel ways to combat its infections. In this work, silver nanoparticles were synthesized in a green way using leaves and fugal extracts and its antibacterial effects were tested against clinical strains. The nanoparticles killed the strains due severe cellular damage affecting the membranes, the DNA and generating reactive oxygen species, in addition they were nontoxic and displayed synergy with some antibiotics; therefore, being a promising alternative to treat MDR P. aeruginosa infections.

No abstract

Fosfomycin is currently a viable option against urinary tract infections, particularly against extended-spectrum β-lactamases (ESBL)-producing E. coli, due to its unique mechanism of action and its low resistance among bacteria. The objective of this study was to investigate two of the three most common mechanisms of resistance against this antibiotic among 350 ESBL-producing E. coli strains isolated from the urine of Mexican patients. The prevalence of fosfomycin resistance in our study was 10.9% (38/350). Of all resistant isolates analyzed, 23 (60.5%) were identified as fos-producing organisms, with 14 strains carrying fosA3 and 9, fosA1. Additionally, 11 (28.9%) fosfomycin-resistant isolates presented resistance due to impaired antibiotic transport and 8 (21.0%) both mechanisms. No resistance mechanism investigated in the study was found on 12 strains. All 38 confirmed ESBL-producing isolates carried a blaCTX-M subtype, 36 (94.5%) belonged to the O25b-ST131 clone, and all of them were able to transfer the fosfomycin resistance trait to recipient strains horizontally. This is the first study in Mexico demonstrating a plasmid-mediated fosfomycin resistance mechanism among clinical E. coli strains. Since our results suggest a strong association among fos and blaCTX-Mgenes and ST131 clones in uropathogenic E. coli, plasmid-mediated fosfomycin resistance should be closely monitored.