Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors.

Xeroderma pigmentosum variant (XP-V) is an autosomal recessive disease with an increased risk of developing cutaneous neoplasms in sunlight-exposed regions. These cells are deficient in the translesion synthesis (TLS) DNA polymerase eta, responsible for bypassing different types of DNA lesions. From the exome sequencing of 11 skin tumors of a genetic XP-V patients' cluster, classical mutational signatures related to sunlight exposure, such as C>T transitions targeted to pyrimidine dimers, were identified.

XPC and POLH/XPV Genes Mutated in a Genetic Cluster of Xeroderma Pigmentosum Patients in Northeast Brazil.

Xeroderma pigmentosum (XP) is a rare genetic condition in which exposure to sunlight leads to a high tumor incidence due to defective DNA repair machinery. Herein, we investigated seven patients clinically diagnosed with XP living in a small city, Montanhas (Rio Grande do Norte), in the Northeast region of Brazil. We performed high-throughput sequencing and, surprisingly, identified two different mutated genes.

Naked (N) mutant mice carry a nonsense mutation in the homeobox of Hoxc13.

Loss of function mutations in HOXC13 have been associated with Ectodermal Dysplasia-9, Hair/Nail Type (ECTD9) in consanguineous families, characterized by sparse to complete absence of hair and nail dystrophy. Here we characterize the spontaneous mouse mutation Naked (N) as a terminal truncation in the Hoxc13 (homeobox C13) gene. Similar to previous reports for homozygous Hoxc13 knock-out (KO) mice, homozygous N/N mice exhibit generalized alopecia with abnormal nails and a short lifespan.

Sensing soluble uric acid by Naip1-Nlrp3 platform.

Uric acid (UA), a product of purine nucleotide degradation able to initiate an immune response, represents a breakpoint in the evolutionary history of humans, when uricase, the enzyme required for UA cleavage, was lost. Despite being inert in human cells, UA in its soluble form (sUA) can increase the level of interleukin-1β (IL-1β) in murine macrophages. We, therefore, hypothesized that the recognition of sUA is achieved by the Naip1-Nlrp3 inflammasome platform.

Open gaps in the evolution of the eukaryotic nucleotide excision repair.

Nucleotide excision repair (NER) is the most versatile DNA repair pathway as it removes different kinds of bulky lesions. Due to its essential role for genome integrity, it has appeared early in the evolution of species. However, most published studies are focused on humans, mice, yeast or bacteria.

Behavioral and neurochemical characterization of the spontaneous mutation tremor, a new mouse model of audiogenic seizures.

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss-Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile.

Chemogenomic study of gemcitabine using Saccharomyces cerevisiae as model cell-molecular insights about chemoresistance.

Gemcitabine (GEM) is the drug used as first line to treat pancreatic cancer, one of the most devastating human tumors. This peculiar type of tumor develops resistance to several drugs, including GEM, due to its desmoplastic reaction and other features. The GEM chemoresistance has been investigated at molecular level aiming to find a pathway whose inhibition or activation should overcome it.

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome.

The recessive mutant mice bate palmas (bapa) - claps in Portuguese arose from N-ethyl-N-nitrosourea mutagenesis. A single nucleotide, T > C, change in exon 13, leading to a Thr Ala substitution, was identified in the lysine (K)-specific methyltransferase 2D gene (Kmt2d) located on chromosome 15. Mutations with a loss-of-function in the KMT2D gene on chromosome 12 in humans are responsible for Kabuki syndrome (KS).

Draft genome sequence of a bla/IncI1-harbouring Escherichia coli D:ST457 isolated from coastal benthic organisms.

Objectives: Marine bivalves can act as bioindicators of marine environment pollution by multidrug-resistant (MDR) enteric bacteria of medical interest. The aim of this study was to report the draft genome sequence of a plasmid-encoded AmpC (pAmpC) (CMY-2)-carrying Escherichia coli isolate recovered from a marine bivalve sample in the coastal shore of Southeast Brazil.

Methods: The whole genome was sequenced on an Illumina NextSeq platform and was assembled using Velvet v.

Draft genome sequence of a CTX-M-8, CTX-M-55 and FosA3 co-producing Escherichia coli ST117/B2 isolated from an asymptomatic carrier.

Objectives: Asymptomatic carriers can act as reservoirs of multidrug-resistant (MDR) bacteria. The aim of this study was to describe the draft genome sequence of a MDR Escherichia coli lineage recovered from a faecal sample of a healthy carrier.

Methods: Genomic DNA was sequenced on an Illumina NextSeq platform.

Draft genome sequence of an extensively drug-resistant Pseudomonas aeruginosa isolate belonging to ST644 isolated from a footpad infection in a Magellanic penguin (Spheniscus magellanicus).

Objectives: The incidence of multidrug-resistant bacteria in wildlife animals has been investigated to improve our knowledge of the spread of clinically relevant antimicrobial resistance genes. The aim of this study was to report the first draft genome sequence of an extensively drug-resistant (XDR) Pseudomonas aeruginosa ST644 isolate recovered from a Magellanic penguin with a footpad infection (bumblefoot) undergoing rehabilitation process.

Methods: The genome was sequenced on an Illumina NextSeq platform using 150-bp paired-end reads.

Genome sequence analysis of a hypermucoviscous/hypervirulent and MDR CTX-M-15/K19/ST29 Klebsiella pneumoniae isolated from human infection.

The emergence of hypervirulent Klebsiella pneumoniae (hvKP) with multidrug resistance (MDR) profile is a worrisome public health issue. We report the first draft genome sequence of a hypermucoviscous (positive string test) and MDR K. pneumoniae serotype K19, belonging to ST29, isolated from human infection.

Draft genome sequences of two fluoroquinolone-resistant CTX-M-15-producing Escherichia coli ST90 (ST23 complex) isolated from a calf and a dairy cow in South America.

Objectives: Farm animals have been recognised as important carriers and reservoirs of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. The aim of this study was to report the draft genome sequences of two multidrug-resistant (MDR) CTX-M-15-producing E. coli strains (47VL and 13B) isolated from different bovine hosts (a calf and a dairy cow), housed separately in a commercial dairy farm in Brazil.

Draft genome sequence of Enterobacter cloacae ST520 harbouring bla, bla and bla isolated from coastal waters of the South Atlantic Ocean.

Objectives: Aquatic environments have contributed to the dissemination of multidrug-resistant (MDR) bacteria, representing a risk for humans and animals. The aim of this study was to report the first draft genome sequence of a MDR Enterobacter cloacae strain recovered from seawater in a public beach in Brazil.

Methods: The genome was sequenced on an Illumina MiSeq platform.

Draft genome sequence of a multidrug-resistant KPC-2-producing Enterobacter aerogenes isolated from a hospitalised patient in Brazil.

Objectives: Multidrug-resistant (MDR) Enterobacter aerogenes strains are frequently associated with nosocomial infections and high mortality rates, representing a serious public health problem. The aim of this study was to present the draft genome sequence of a MDR KPC-2-producing E. aerogenes isolated from a perineal swab of a hospitalised patient in Brazil.

Draft genome sequence of a multidrug-resistant Aeromonas hydrophila ST508 strain carrying rmtD and bla isolated from a bloodstream infection.

Here we report the draft genome sequence of a multidrug-resistant (MDR) Aeromonas hydrophila strain belonging to sequence type 508 (ST508) isolated from a human bloodstream infection. Assembly and annotation of this draft genome resulted in 5028498bp and revealed the presence of 16S rRNA methylase rmtD and bla genes encoding high-level resistance to aminoglycosides and cephalosporins, respectively, as well as multiple virulence genes. This draft genome can provide significant information for understanding mechanisms on the establishment and treatment of infections caused by this pathogen.

Draft genome sequence of a CTX-M-15-producing Escherichia coli ST345 from commercial chicken meat in Brazil.

Escherichia coli, the main host of the CTX-M-15 extended-spectrum β-lactamase (ESBL) enzyme, is widely distributed and exchanged between the environment, animals and humans. Therefore, identification of bla-positive lineages in food has a significant impact on public health. In this regard, until the end of 1990s, ESBL-producing isolates were mainly associated with hospital-acquired infections, with a predominance of SHV- and TEM-type enzymes.

Draft Genome Sequences of Colistin-Resistant MCR-1-Producing ST1850 and ST74 Strains Isolated from Commercial Chicken Meat.

We present here the draft genome sequences of two colistin-resistant -carrying strains belonging to sequence type 74 (ST74) and ST1850, isolated from commercial chicken meat in Brazil. Assembly of this draft genome resulted in 5,022,083 and 4,950,681 bp, respectively, revealing the presence of the IncX4 plasmid-mediated gene responsible for resistance to colistin.

Draft genome sequence of an aminoglycoside-resistant RmtG-producing Pseudomonas aeruginosa ST235 isolated from a cystic fibrosis patient.

Cystic fibrosis (CF) patients are often chronically colonised or infected by non-fermenting Gram-negative bacilli, with Pseudomonas aeruginosa being the most prevalent. In this study, we report the draft genome sequence of a multidrug-resistant P. aeruginosa strain belonging to sequence type ST235, isolated from the respiratory tract of a CF patient with chronic colonisation.

Draft genome sequence of an environmental multidrug-resistant Klebsiella pneumoniae ST340/CC258 harbouring bla and bla genes.

Anthropogenic activities, including the release of wastewater and sewage from hospitals, have contributed to the contamination of aquatic environments, raising a concern to public health. In this study, we present the first draft genome sequence of a Klebsiella pneumoniae strain (Kp171, TIET-4200) belonging to the high-risk hospital-associated clonal lineage ST340/CC258, which was recovered from a water sample collected in an urban river in Brazil.

Draft Genome Sequence of a Hospital-Associated Clone of Klebsiella pneumoniae ST340/CC258 Coproducing RmtG and KPC-2 Isolated from a Pediatric Patient.

We report here the draft genome sequence of a Klebsiella pneumoniae strain 1194/11, belonging to the hospital-associated sequence type 340 (ST340; clonal complex CC258), isolated from a catheter tip culture from a pediatric patient. The multidrug-resistant strain coproduced the 16S rRNA methyltransferase rRNA RmtG and β-lactamases KPC-2 and CTX-M-15.