Comparative Genomics of Pseudomonas aeruginosa Strains Isolated from Different Ecological Niches.

The Pseudomonas aeruginosa genome can change to adapt to different ecological niches. We compared four genomes from a Mexican hospital and 59 genomes from GenBank from different niches, such as urine, sputum, and environmental. The ST analysis showed that high-risk STs (ST235, ST773, and ST27) were present in the genomes of the three niches from GenBank, and the STs of Mexican genomes (ST167, ST2731, and ST549) differed from the GenBank genomes. Phylogenetic analysis showed that the genomes were clustering according to their ST and not their niche. When analyzing the genomic content, we observed that environmental genomes had genes involved in adapting to the environment not found in the clinics and that their mechanisms of resistance were mutations in antibiotic resistance-related genes. In contrast, clinical genomes from GenBank had resistance genes, in mobile/mobilizable genetic elements in the chromosome, except for the Mexican genomes that carried them mostly in plasmids. This was related to the presence of CRISPR-Cas and anti-CRISPR; however, Mexican strains only had plasmids and CRISPR-Cas. blaOXA-488 (a variant of blaOXA50) with higher activity against carbapenems was more prevalent in sputum genomes. The virulome analysis showed that exoS was most prevalent in the genomes of urinary samples and exoU and pldA in sputum samples. This study provides evidence regarding the genetic variability among P. aeruginosa isolated from different niches.

A Plasmid Carrying blaIMP-56 in Pseudomonas aeruginosa Belonging to a Novel Resistance Plasmid Family.

blaIMP and blaVIM are the most detected plasmid-encoded carbapenemase genes in Pseudomonas aeruginosa. Previous studies have reported plasmid sequences carrying blaIMP variants, except blaIMP-56. In this study, we aimed to characterize a plasmid carrying blaIMP-56 in a P. aeruginosa strain isolated from a Mexican hospital. The whole genome of P. aeruginosa strain PE52 was sequenced using Illumina Miseq 2 × 150 bp, with 5 million paired-end reads. We characterized a 27 kb plasmid (pPE52IMP) that carried blaIMP-56. The phylogenetic analysis of RepA in pPE52IMP and 33 P. aeruginosa plasmids carrying resistance genes reported in the GenBank revealed that pPE52IMP and four plasmids (pMATVIM-7, unnamed (FDAARGOS_570), pD5170990, and pMRVIM0713) were in the same clade. These closely related plasmids belonged to the MOBP11 subfamily and had similar backbones. Another plasmid (p4130-KPC) had a similar backbone to pPE52IMP; however, its RepA was truncated. In these plasmids, the resistance genes blaKPC-2, blaVIM variants, aac(6')-Ib4, blaOXA variants, and blaIMP-56 were inserted between phd and resolvase genes. This study describes a new family of plasmids carrying resistance genes, with a similar backbone, the same RepA, and belonging to the MOBP11 subfamily in P. aeruginosa. In addition, our characterized plasmid harboring blaIMP-56 (pPE52IMP) belongs to this family.

Characterization of antimicrobial resistance mechanisms in carbapenem-resistant Pseudomonas aeruginosa carrying IMP variants recovered from a Mexican Hospital.

PURPOSE: Pseudomonas aeruginosa infections in hospitals constitute an important problem due to the increasing multidrug resistance (MDR) and carbapenems resistance. The knowledge of resistance mechanisms in Pseudomonas strains is an important issue for an adequate antimicrobial treatment. Therefore, the objective was to investigate other antimicrobial resistance mechanisms in MDR P. aeruginosa strains carrying bla IMP, make a partial plasmids characterization, and determine if modifications in oprD gene affect the expression of the OprD protein. METHODOLOGY: Susceptibility testing was performed by Kirby Baüer and by Minimum Inhibitory Concentration (presence/absence of efflux pump inhibitor); molecular typing by Pulsed-field gel electrophoresis (PFGE), resistance genotyping and integrons by PCR and sequencing; OprD expression by Western blot; plasmid characterization by MOB Typing Technique, molecular size by PFGE-S1; and bla IMP location by Southern blot. RESULTS: Among the 59 studied P. aeruginosa isolates, 41 multidrug resistance and carbapenems resistance isolates were detected and classified in 38 different PFGE patterns. Thirteen strains carried bla IMP; 16 bla GES and four carried both genes. This study centered on the 17 strains har-boring bla IMP. New variants of ß-lactamases were identified (bla GES-32, bla IMP-56, bla IMP-62) inside of new arrangements of class 1 integrons. The presence of bla IMP gene was detected in two plasmids in the same strain. The participation of the OprD protein and efflux pumps in the resistance to carbapenems and quinolones is shown. No expression of the porin OprD due to stop codon or IS in the gene was found. CONCLUSIONS: This study shows the participation of different resistance mechanisms, which are reflected in the levels of MIC to carbapenems. This is the first report of the presence of three new variants of ß-lactamases inside of new arrangements of class 1 integrons, as well as the presence of two plasmids carrying bla IMP in the same P. aeruginosa strain isolated in a Mexican hospital.

Aspectos genéticos de los Feocromocitomas y Paragangliomas / Genetic aspects of Pheocromocytomas and Paragangliomas

Los Feocromocitomas (FCC) y Paragangliomas (PGG) son tumores derivados de células de la cresta neural, que secretan catecolaminas. El 80-85% de los FCC derivan de la médula adrenal, mientras el 15-20% de tejido cromafín extra adrenal. Avances en la investigación genética han permitido identificar múltiples genes implicados en la fisiopatogenia de estos tumores, de forma que podrían tener una mutación germinal subyacente. La existencia de mutaciones espontáneas, baja penetrancia, protección materna e interacciones entre genes o con el ambiente puede explicar en parte este hecho. Debe confirmarse, la existencia de una mutación en un paciente afecto antes de ofrecer estudio genético a sus familiares asintomáticos. El clínico debe considerar diversos factores como: la localización del tumor, producción hormonal, malignidad, multicentricidad e historia familiar antes de decidir que mutación debe estudiarse en primer lugar. Un diagnóstico precoz de estos tumores, acompañado de un correcto diagnóstico genético, debe ser una prioridad que permita un mejor tratamiento, la detección precoz de complicaciones, un correcto tamizaje de familiares y de otros tumores relacionados, así como una mejoría en el pronóstico global de estos pacientes. El brindar conocimiento de nuevos genes causantes de la enfermedad hereditaria ha supuesto un cambio en las recomendaciones sobre la necesidad de realizar estudio genético para brindar el tratamiento adecuado a tiempo.(AU)

Pheochromocytomas (FCC) and Paragangliomas (PGG) are tumors derived from neural crest cells, which secrete catecholamines. 80-85% of FCCs derive from the adrenal medulla, while 15-20% from extra-adrenal chromaffin tissue. Advances in genetic research have made it possible to identify multiple genes involved in the physiopathogenesis of these tumors, such that they could have an underlying germline mutation. The existence of spontaneous mutations, low penetrance, maternal protection and interactions between genes or with the environment can partly explain this fact. The existence of a mutation in an affected patient must be confirmed before offering a genetic study to their asymptomatic relatives. The clinician must consider several factors such as: tumor location, hormonal production, malignancy, multicentricity, and family history before deciding which mutation should be studied first. An early diagnosis of these tumors, accompanied by a correct genetic diagnosis, should be a priority that allows better treatment, the early detection of complications, a correct screening of relatives and other related tumors, as well as an improvement in the overall prognosis of these patients. Providing knowledge of new genes that cause hereditary disease has led to a change in the recommendations regarding the need for a genetic study to provide the appropriate treatment in time.(AU)