RESUMO
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. However, basal cell carcinomas also showed distinct C>A mutation spectra reflecting a mutational signature possibly related to sunlight-induced oxidative stress. Moreover, four samples carry different mutational signatures, with C>A mutations associated with tobacco chewing or smoking usage. Thus, XP-V patients should be warned of the risk of these habits. Surprisingly, higher levels of retrotransposon somatic insertions were also detected when the tumors were compared with non-XP skin tumors, revealing other possible causes for XP-V tumors and novel functions for the TLS polymerase eta in suppressing retrotransposition. Finally, the expected high mutation burden found in most of these tumors renders these XP patients good candidates for checkpoint blockade immunotherapy.
Assuntos
Neoplasias Cutâneas , Xeroderma Pigmentoso , Humanos , Xeroderma Pigmentoso/genética , Retroelementos/genética , Mutação , Reparo do DNA , Neoplasias Cutâneas/genética , Raios Ultravioleta/efeitos adversosRESUMO
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 Thr1289 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). Phenotypic characterization of the bapa mutant was performed using a behavioral test battery to evaluate the parameters related to general activity, the sensory nervous system, the psychomotor system, and the autonomous nervous system, as well as to measure motor function and spatial memory. Relative to BALB/cJ mice, the bapa mutant showed sensory and psychomotor impairments, such as hypotonia denoted by a surface righting reflex impairment and hindquarter fall, and a reduction in the auricular reflex, suggesting hearing impairment. Additionally, the enhanced general activity showed by the increased rearing and grooming frequency, distance traveled and average speed possibly presupposes the presence of hyperactivity of bapa mice compared with the control group. A slight motor coordination dysfunction was showed in bapa mice, which had a longer crossing time on the balance beam compared with BALB/cJ controls. Male bapa mice also showed spatial gait pattern changes, such as a shorter stride length and shorter step length. In conclusion, the bapa mouse may be a valuable animal model to study the mechanisms involved in psychomotor and behavior impairments, such as hypotonia, fine motor coordination and hyperactivity linked to the Kmt2d mutation.
Assuntos
Anormalidades Múltiplas/genética , Comportamento Animal , Face/anormalidades , Doenças Hematológicas/genética , Histona-Lisina N-Metiltransferase/genética , Mutação com Perda de Função , Proteína de Leucina Linfoide-Mieloide/genética , Doenças Vestibulares/genética , Anormalidades Múltiplas/fisiopatologia , Animais , Modelos Animais de Doenças , Face/fisiopatologia , Marcha , Audição , Doenças Hematológicas/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Movimento , Hipotonia Muscular/genética , Reflexo , Doenças Vestibulares/fisiopatologiaRESUMO
OBJECTIVES: KPC-producing Klebsiella pneumoniae is considered one of the most worrisome multidrug-resistant micro-organisms in nosocomial infections. It has also been reported in wastewater and urban rivers in the city of Sao Paulo, Brazil. Here we report the draft genome sequences of three KPC-2- and CTX-M-15-producing K. pneumoniae sequence type 437 (ST437) isolates obtained from two urban rivers and from a clinical sample of a patient in Sao Paulo. METHODS: A genomic library was constructed using a Nextera XT Kit. An Illumina platform was used to perform whole-genome sequencing (WGS). RESULTS: WGS of environmental isolates Kp148/PINH-4900 and Kp196/TIET-4200 and clinical isolate Kp314/11 resulted in estimated genome sizes of 5464058, 5437723 and 5319218bp, respectively. Resistome analysis of the environmental and clinical strains revealed the presence of resistance genes to the following antimicrobials in all strains: aminoglycosides [aac(6')-Ib-cr]; ß-lactams (blaOXA-1, blaSHV-11, blaCTX-M-15 and blaKPC-2); fluoroquinolones [aac(6')-Ib-cr, oqxA and oqxB]; fosfomycin (fosAKP); macrolides [mph(A)]; phenicols (catB4); sulfonamides (sul1); and trimethoprim (dfrA30). The tetracycline resistance gene tetA was identified in Kp148/PINH-4900 and Kp314/11 only; the aminoglycoside resistance gene aph(3')-Ia was found only in environmental isolates, and aadA2 only in Kp314/11; and the phenicol resistance gene catA1 was identified only in Kp148/PINH-4900. CONCLUSIONS: The draft genome sequences of these strains help us to elucidate the dissemination of resistance genes in micro-organisms inside and outside the hospital and are useful for further comparisons between clinical and environmental strains.
Assuntos
Genoma Bacteriano , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Parques Recreativos , Rios/microbiologia , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Brasil , Farmacorresistência Bacteriana Múltipla , Humanos , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Análise de Sequência de DNA , Sequenciamento Completo do Genoma , beta-Lactamases/genéticaRESUMO
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.1.2.10. Data analysis was carried out using tools available from the Center of Genomic Epidemiology and Geneious R10 software. RESULTS: The genome size was calculated at 5198055bp, comprising a total of 5316 protein-coding sequences. The strain was assigned to ST457 and presented the blaCMY-2 pAmpC gene. In addition, the strain was clustered into the pathogenic phylogenetic group D. CONCLUSION: The release of this draft genome sequence can provide valuable information to better understand the dissemination of MDR enteric bacteria in marine environments.
Assuntos
Bivalves/microbiologia , Farmacorresistência Bacteriana Múltipla , Escherichia coli/genética , Genoma Bacteriano , Animais , Proteínas de Bactérias/genética , Brasil , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Filogenia , Plasmídeos/genética , Análise de Sequência de DNA , Sequenciamento Completo do Genoma , beta-Lactamases/genéticaRESUMO
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. This strain harboured multiple antimicrobial resistance genes, including blaCTX-M-15, besides yersiniabactin and type 3 fimbriae virulence genes. In vivo experiments carried out with the Galleria mellonella infection model revealed that K. pneumoniae K19/ST29 killed 100% of the larvae at 24 h post-infection, in a similar way to the known hypermucoviscous hvKP K1/ST23 lineage.
Assuntos
Genoma Bacteriano , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Análise de Sequência de DNA , beta-Lactamases/metabolismo , Animais , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla , Humanos , Klebsiella pneumoniae/isolamento & purificação , Larva/microbiologia , Larva/fisiologia , Lepidópteros/microbiologia , Lepidópteros/fisiologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Virulência , Fatores de Virulência/genéticaRESUMO
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. METHODS: Genomic DNA was sequenced using an Illumina MiSeq platform. De novo genome assembly was carried out using the A5-Miseq pipeline, and whole-genome sequence analysis was performed using tools from the Center for Genomic Epidemiology. RESULTS: The strain harboured resistance genes to ß-lactams, aminoglycosides, sulphonamides and trimethoprim in addition to genes encoding multidrug efflux system proteins, a quaternary ammonium transporter and heavy metal efflux system proteins. In addition, the strain harboured genes encoding diverse virulence factors. CONCLUSION: These data might allow a better understanding of the genetic basis of antimicrobial resistance and virulence in E. aerogenes strains.
Assuntos
Farmacorresistência Bacteriana Múltipla , Enterobacter aerogenes/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Sequenciamento Completo do Genoma/métodos , Brasil , Enterobacter aerogenes/genética , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Hospitalização , Humanos , Fatores de Virulência/genéticaRESUMO
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. De novo genome assembly was performed using SPAdes 3.10.1 and the whole genome sequence was analysed using bioinformatics tools from the Center of Genomic Epidemiology. RESULTS: This draft genome resulted in 5 228 857bp with 5331 protein-coding sequences, revealing the presence of blaKPC-2, blaCTX-M-15 and blaOXA-17 genes, responsible for resistance to all ß-lactam antibiotics. In addition, the strain was assigned to sequenced type 520 (ST520). CONCLUSION: These data provide useful information for comparative genomic analysis regarding the dissemination of antibiotic resistance genes.
Assuntos
Farmacorresistência Bacteriana Múltipla , Enterobacter cloacae/classificação , Sequenciamento Completo do Genoma/métodos , beta-Lactamases/genética , Oceano Atlântico , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Praias , Brasil , Enterobacter cloacae/genética , Genoma Bacteriano , Tipagem de Sequências Multilocus , Microbiologia da ÁguaRESUMO
Escherichia coli, the main host of the CTX-M-15 extended-spectrum ß-lactamase (ESBL) enzyme, is widely distributed and exchanged between the environment, animals and humans. Therefore, identification of blaCTX-M-15-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. In recent years, a new trend has been observed among ESBL-producers, where most isolates now harbour CTX-M-type, being further isolated from community-acquired infections. Nowadays, CTX-M-15 has been recognised as the most important ESBL variant, invading virtually all human and animal compartments, leading to a global pandemic. Thus, whilst the rapid emergence and dissemination of CTX-M-15 among E. coli isolates has generated a large genetic reservoir from which other members of the Enterobacteriaceae family can easily acquire this resistance gene, there are an increasing number of new reservoirs and transmission mechanisms that must be investigated. In this study, we present the draft genome sequence of a CTX-M-15-producing E. coli ST345 isolated from commercial chicken meat in Brazil. This draft genome can be used as a reference sequence for comparative analysis among CTX-M-15-producers.
Assuntos
Escherichia coli/genética , Escherichia coli/isolamento & purificação , Genoma Bacteriano , Carne/microbiologia , Análise de Sequência de DNA , Sequenciamento Completo do Genoma , beta-Lactamases/metabolismo , Animais , Brasil , Galinhas , Farmacorresistência Bacteriana , Escherichia coli/enzimologia , Genes Bacterianos , Anotação de Sequência MolecularRESUMO
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.
Assuntos
Farmacorresistência Bacteriana Múltipla , Genoma Bacteriano , Klebsiella pneumoniae/genética , Rios/microbiologia , Análise de Sequência de DNA , Brasil , Cidades , Genótipo , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/isolamento & purificação , Tipagem MolecularRESUMO
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. Whole-genome sequencing analysis revealed a 6.7Mb genome size and the presence of 12 antibiotic resistance genes, including the rmtG gene conferring high-level aminoglycoside resistance, located on the chromosome.