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1.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34864885

RESUMO

To better understand the potential of drug repurposing in COVID-19, we analyzed control strategies over essential host factors for SARS-CoV-2 infection. We constructed comprehensive directed protein-protein interaction (PPI) networks integrating the top-ranked host factors, the drug target proteins and directed PPI data. We analyzed the networks to identify drug targets and combinations thereof that offer efficient control over the host factors. We validated our findings against clinical studies data and bioinformatics studies. Our method offers a new insight into the molecular details of the disease and into potentially new therapy targets for it. Our approach for drug repurposing is significant beyond COVID-19 and may be applied also to other diseases.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Biologia Computacional , Reposicionamento de Medicamentos , Mapas de Interação de Proteínas , SARS-CoV-2 , Antivirais/química , Antivirais/farmacocinética , COVID-19/genética , COVID-19/metabolismo , Humanos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
2.
Int J Mol Sci ; 25(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38928058

RESUMO

Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients suffering from SSD are at risk of developing life-threatening complications. Pharmacogenetic studies have shown promising results on personalized treatment of psychosis. In the current study, 103 patients diagnosed with SSD treated with risperidone as antipsychotic monotherapy were enrolled. Socio-demographics and clinical data were recorded, and laboratory tests and genotyping standard procedure for cytochrome P450 (CYP) 2D6*4 were performed. Patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) on admission and at discharge. Based on the reduction in the PANSS total score, subjects were divided into non-responders, partial responders and full responders. Only 11 subjects had a full response to risperidone (10.67%), 53 subjects (51.45%) had a partial response, and 39 participants (37.86%) were non-responders. Patients at first episode psychosis showed significantly higher levels of blood glucose and prolactin levels, while chronic patients showed significantly higher LDL levels. Adverse drug reactions (ADR) such as tremor and stiffness significantly correlated with genetic phenotypes (p = 0.0145). While CYP2D6 showed no impact on treatment response, ADR were significantly more frequent among poor and intermediate metabolizers.


Assuntos
Antipsicóticos , Citocromo P-450 CYP2D6 , Risperidona , Esquizofrenia , Humanos , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Masculino , Feminino , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Pessoa de Meia-Idade , Genótipo , Adulto Jovem
3.
Medicina (Kaunas) ; 60(6)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38929507

RESUMO

Background: Preeclampsia (PE) is a critical condition affecting pregnancies worldwide. Understanding its etiology, particularly the genetic factors, is vital. This study aims to investigate the association between ACE gene polymorphisms, specifically the ACE G2350A (rs4343) variant, and the predisposition to PE, offering insights into the genetic predisposition towards this complex condition. Methods: A case-control study was conducted with 140 participants without PE (Control Group) and 128 participants diagnosed with PE (PE Group). The study focused on comparing the prevalence of the rs4343 polymorphism between the groups. Results: The analysis identified a significantly reduced risk associated with the AG genotype and an insignificant increase in risk with the AA genotype. Statistically significant differences in demographic and clinical characteristics, such as BMI and marital status, were observed between the groups, suggesting a multifaceted risk profile for PE that includes genetic, environmental, and socio-economic factors. Conclusions: The study highlight the significant role of genetic variations, specifically the ACE G2350A (rs4343) polymorphism, in influencing PE predisposition. It highlights the intricate interplay between genetic predispositions and other risk factors in the development of PE. Further research is encouraged to expand on these findings and explore a wider range of genetic polymorphisms and their interactions with environmental factors.


Assuntos
Predisposição Genética para Doença , Pré-Eclâmpsia , Humanos , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/epidemiologia , Feminino , Gravidez , Estudos de Casos e Controles , Adulto , Fatores de Risco , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Fatores Socioeconômicos , Genótipo , Polimorfismo de Nucleotídeo Único
4.
Chirurgia (Bucur) ; 116(4): 424-430, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34498562

RESUMO

Introduction: We present our 6-year experience with liver surgery and ablative techniques. Method: An observational retrospective analysis from a prospectively maintained database was performed in our department. All the patients with liver resection, liver resection combined with intraoperative ablative techniques and percutaneous ablative techniques were included from January 1st 2014 to December 31st 2020. Results: There were 249 patients analyzed: 273 patients with liver resection, 12 patients with liver resection combined with intraoperative MWA, 9 patients with open surgery MWA, 12 patients with percutaneous MWA, 1 patient with TACE and MWA, 1 patient with TACE and PEI, 10 patients with TACE, and 2 patients with PEI. Conclusion: Liver disease should be managed in specialized centers which can offer a wide range of therapeutic options. With the improvement of the surgical technique and perioperative care, including optimized postoperative complication management, and carried out by well-trained surgeons, liver surgery can be performed with low mortality and acceptable morbidity.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
5.
Chirurgia (Bucur) ; 115(6): 735-746, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33378632

RESUMO

Introduction: We present our department experience in pancreatic surgery over the last 6 years. From its inception the number of pancreatic resections has been continuously growing each year. Method: We performed a retrospective analysis of a prospectively maintained database where we included all the patients with pancreatic resections over the last 6 years. We present the main indication and the different types of pancreatic resections, postoperative morbidity, intrahospital and 90-day mortality and an analysis of survival for the patients with pancreatic ductal adenocarcinoma. Results: We analyzed 198 patients, 193 with pancreatic resections and 5 patients with open surgery microwave ablation. There were 145 pancreaticoduodenectomies, 37 distal pancreatectomies, one total pancreatectomy, 3 distal pancreatectomies with celiac axis resection and 7 surgical interventions for chronic pancreatitis. Conclusion: We presented our center's experience in pancreatic surgery with good overall results, however, there is still room for continuous improvement and refinements to achieve better shortterm outcomes, regarding postoperative morbidity and mortality.


Assuntos
Carcinoma Ductal Pancreático , Pancreatectomia , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Técnicas de Ablação , Carcinoma Ductal Pancreático/cirurgia , Humanos , Micro-Ondas/uso terapêutico , Neoplasias Pancreáticas/cirurgia , Pancreatite Crônica/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Chirurgia (Bucur) ; 112(3): 229-243, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28675359

RESUMO

Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list.


Assuntos
Hepatopatias/cirurgia , Transplante de Fígado , Doadores Vivos , Listas de Espera , Adolescente , Adulto , Idoso , Cadáver , Criança , Pré-Escolar , Doença Hepática Terminal/cirurgia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Lactente , Comunicação Interdisciplinar , Hepatopatias/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Romênia , Resultado do Tratamento
7.
Immun Inflamm Dis ; 11(8): e930, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37647436

RESUMO

BACKGROUND: The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease resulting from loss-of-function mutations in ADA2, formerly named CECR1 (cat eye syndrome chromosome region, candidate 1) gene. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory, and hematologic; however, most patients presented with significant overlap between these three phenotype groups. CASE PRESENTATION: We present a case of DADA2 deficiency with disease onset at 3 years old, not recognized till the age of 18 with severe gastrointestinal vasculitis and recurrent episodes of neutropenia associated with a new CECR1 mutation.


Assuntos
Adenosina Desaminase , Peptídeos e Proteínas de Sinalização Intercelular , Adenosina Desaminase/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação
8.
J Clin Med ; 11(11)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35683539

RESUMO

Saliva is in the first line of the body's defense mechanism. In order to better understand how liver transplantation impacts salivary biochemistry, the aim of this cross-sectional study was to explore variations of salivary markers for oral health in post-liver transplantation patients, as compared with systemically healthy dental outpatients (controls). In this case, 26 patients were enrolled in each group, with similar socio-demographic characteristics. Unstimulated whole saliva was collected; total protease activity and total protein content were measured. The oral health in both groups was assessed using a self-report oral health questionnaire. Data were analyzed using parametric and nonparametric tests. Comparable results were recorded in terms of salivary protein and protease activity assessments. In post-liver transplantation group, positive correlation was found between the salivary pH level and the salivary secretion rate (r = 0.39; p = 0.04). With respect to self-reported oral health, there were no significant differences between the two groups, except for dental and oral care habits, the controls reporting more frequently use of dental floss and mouthwash (p = 0.02, and p = 0.003, respectively). Considering the high risk for developing systemic complications after liver transplantation, oral health care is an important issue to be addressed, salivary investigations representing powerful tool for disease changes monitoring.

9.
Antimicrob Resist Infect Control ; 11(1): 115, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104761

RESUMO

BACKGROUND: Romania is one of the European countries reporting very high antimicrobial resistance (AMR) rates and consumption of antimicrobials. We aimed to characterize the AMR profiles and clonality of 304 multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) strains isolated during two consecutive years (2018 and 2019) from hospital settings, hospital collecting sewage tanks and the receiving wastewater treatment plants (WWTPs) located in the main geographical regions of Romania. METHODS: The strains were isolated on chromogenic media and identified by MALDI-TOF-MS. Antibiotic susceptibility testing and confirmation of ESBL- and CP- producing phenotypes and genotypes were performed. The genetic characterization also included horizontal gene transfer experiments, whole-genome sequencing (WGS), assembling, annotation and characterization. RESULTS: Both clinical and aquatic isolates exhibited high MDR rates, especially the Ab strains isolated from nosocomial infections and hospital effluents. The phenotypic resistance profiles and MDR rates have largely varied by sampling point and geographic location. The highest MDR rates in the aquatic isolates were recorded in Galați WWTP, followed by Bucharest. The Ab strains harbored mostly blaOXA-23, blaOXA-24, blaSHV, blaTEM and blaGES, while Pa strains blaIMP, blaVIM, blaNDM, blaVEB, blaGES and blaTEM, with high variations depending on the geographical zone and the sampling point. The WGS analysis revealed the presence of antibiotic resistance genes (ARGs) to other antibiotic classes, such as aminoglycosides, tetracyclines, sulphonamides, fosfomycin, phenicols, trimethoprim-sulfamethoxazole as well as class 1 integrons. The molecular analyses highlighted: (i) The presence of epidemic clones such as ST2 for Ab and ST233 and ST357 for Pa; (ii) The relatedness between clinical and hospital wastewater strains and (iii) The possible dissemination of clinical Ab belonging to ST2 (also proved in the conjugation assays for blaOXA-23 or blaOXA-72 genes), ST79 and ST492 and of Pa strains belonging to ST357, ST640 and ST621 in the wastewaters. CONCLUSION: Our study reveals the presence of CP-producing Ab and Pa in all sampling points and the clonal dissemination of clinical Ab ST2 strains in the wastewaters. The prevalent clones were correlated with the presence of class 1 integrons, suggesting that these isolates could be a significant reservoir of ARGs, being able to persist in the environment.


Assuntos
Acinetobacter baumannii , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Hospitais , Proteína 1 Semelhante a Receptor de Interleucina-1 , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , Romênia/epidemiologia , Águas Residuárias/microbiologia , Vigilância Epidemiológica Baseada em Águas Residuárias , beta-Lactamases/genética
10.
Pharmaceutics ; 13(2)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540560

RESUMO

Decades of antibiotic misuse in clinical settings, animal feed, and within the food industry have led to a concerning rise in antibiotic-resistant bacteria. Every year, antimicrobial-resistant infections cause 700,000 deaths, with 10 million casualties expected by 2050, if this trend continues. Hence, innovative solutions are imperative to curb antibiotic resistance. Bacteria produce a potent arsenal of drugs with remarkable diversity that are all distinct from those of current antibiotics. Bacteriocins are potent small antimicrobial peptides synthetized by certain bacteria that may be appointed as alternatives to traditional antibiotics. These molecules are strategically employed by commensals, mostly Firmicutes, to colonize and persist in the human gut. Bacteriocins form channels in the target cell membrane, leading to leakage of low-molecular-weight, causing the disruption of the proton motive force. The objective of this review was to list and discuss the potential of bacteriocins as antimicrobial therapeutics for infections produced mainly by resistant pathogens.

11.
Healthcare (Basel) ; 9(6)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207703

RESUMO

Dementia is a general term for a series of medical conditions that affect the brain and evolve progressively. According to the literature, there are over 200 subtypes and causes of dementia, with Alzheimer's disease (AD) being the most common in elderly people. AD is an irreversible progressive neurodegenerative condition that leads to a decline in mental function, enough to disrupt daily life. Thinking skills slowly deteriorate, which, in advanced stages, makes it impossible to perform simple tasks. Besides the change in the quality of life of AD patients and their families, there is a considerable alteration in the quality of life of their caregivers, whose health can be negatively affected by the development of mental and somatic disorders. This article reviews the literature in order to reveal the benefits of applying non-pharmacological interventions such as music and art therapy to improve quality of life. This article also aims to shed light on the impact of this disease on the caregiver's life. Music and art therapy have produced reliable results in the treatment of patients with AD, and the best effects are related to increased socialization and the maintenance of social status.

12.
Sci Rep ; 11(1): 13288, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168184

RESUMO

Acinetobacter baumannii has emerged worldwide as a dominant pathogen in a broad range of severe infections, raising an acute need for efficient antibacterials. This is the first report on the resistome and virulome of 33 extended drug-resistant and carbapenem-resistant A. baumannii (XDR CRAB) strains isolated from hospitalized and ambulatory patients in Bucharest, Romania. A total of 33 isolates were collected and analyzed using phenotypic antibiotic susceptibility and conjugation assays, PCR, whole-genome sequencing (WGS), pulsed-field gel electrophoresis (PFGE) and MultiLocus Sequence Typing (MLST). All isolates were extensively drug-resistant (XDR), being susceptible only to colistin. The carbapenem resistance was attributed by PCR mainly to blaOXA-24 and blaOXA-23 genes. PFGE followed by MLST analysis demonstrated the presence of nine pulsotypes and six sequence types. WGS of seven XDR CRAB isolates from healthcare-associated infections demonstrated the high diversity of resistance genes repertoire, as well as of mobile genetic elements, carrying ARGs for aminoglycosides, sulphonamides and macrolides. Our data will facilitate the understanding of resistance, virulence and transmission features of XDR AB isolates from Romanian patients and might be able to contribute to the implementation of appropriate infection control measures and to develop new molecules with innovative mechanisms of action, able to fight effectively against these bugs, for limiting the spread and decreasing the infection rate and mortality.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/patogenicidade , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Eletroforese em Gel de Campo Pulsado , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Romênia/epidemiologia , Virulência , Sequenciamento Completo do Genoma
13.
PLoS One ; 16(2): e0246478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33529240

RESUMO

Chronic infections represent an important burden on the healthcare system and have a significant impact on the patients' quality of life. While Staphylococcus spp. are commensal bacteria, they can become pathogenic, leading to various types of infections. In this study we aimed to characterize the virulence profiles of staphylococcal strains involved in difficult-to-treat skin and soft tissue infections, from both phenotypic and genotypic points of view. Phenotypic ability of the strains to secrete soluble virulence factors was assessed by a culturing dependent assay and their capacity to develop biofilms on inert substrate was screened by an adapted crystal violet microtiter method. We also tested the presence of several virulence genes by PCR. Most of the studied strains were isolated from purulent secretions of acne lesions and frequently secreted two or three soluble virulence factors. Most frequently secreted soluble virulence factors were caseinase (89%), lipase (71%) and lecithinase (67%). Almost half of the strains produced a well-represented biofilm. The molecular characterization showed the presence of the genes cna, hlg, clfA, and clfB. Staphylococcal strains that produce difficult-to-treat skin and soft tissue infections seem to be characterized by an enhanced ability to produce different soluble virulence factors and to develop biofilms in vitro. Further studies need to be developed in other Staphylococcus spp. infections in order to confirm this hypothesis.


Assuntos
Staphylococcus/patogenicidade , Biofilmes , Genótipo , Humanos , Lipase/genética , Lipase/metabolismo , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Fosfolipases/genética , Fosfolipases/metabolismo , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus/genética , Staphylococcus/metabolismo , Virulência , Fatores de Virulência
14.
Solid State Nucl Magn Reson ; 38(1): 31-5, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20605083

RESUMO

We have measured the solid state nuclear magnetic resonance (NMR) 1H spin-lattice relaxation rate from 93 to 340 K at NMR frequencies of 8.5 and 53 MHz in 5-t-butyl-4-hydroxy-2-methylphenyl sulfide. We have also determined the molecular and crystal structures from X-ray diffraction experiments. The relaxation is caused by methyl and t-butyl group rotation modulating the spin-spin interactions and we relate the NMR dynamical parameters to the structure. A successful fit of the data requires that the 2-methyl groups are rotating fast (on the NMR time scale) even at the lowest temperatures employed. The rotational barrier for the two out-of-plane methyl groups in the t-butyl groups is 14.3+/-2.7 kJ mol(-1) and the rotational barrier for the t-butyl groups and their in-plane methyl groups is 24.0+/-4.6 kJ mol(-1). The uncertainties account for the uncertainties associated with the relationship between the observed NMR activation energy and a model-independent barrier, as well as the experimental uncertainties.


Assuntos
Butanos/química , Espectroscopia de Ressonância Magnética/métodos , Metano/química , Prótons , Modelos Moleculares , Conformação Molecular , Temperatura
15.
Front Microbiol ; 11: 761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32435238

RESUMO

Antimicrobial resistance (AMR) is a significant global threat to both public health and the environment. The emergence and expansion of AMR is sustained by the enormous diversity and mobility of antimicrobial resistance genes (ARGs). Different mechanisms of horizontal gene transfer (HGT), including conjugation, transduction, and transformation, have facilitated the accumulation and dissemination of ARGs in Gram-negative and Gram-positive bacteria. This has resulted in the development of multidrug resistance in some bacteria. The most clinically significant ARGs are usually located on different mobile genetic elements (MGEs) that can move intracellularly (between the bacterial chromosome and plasmids) or intercellularly (within the same species or between different species or genera). Resistance plasmids play a central role both in HGT and as support elements for other MGEs, in which ARGs are assembled by transposition and recombination mechanisms. Considering the crucial role of MGEs in the acquisition and transmission of ARGs, a potential strategy to control AMR is to eliminate MGEs. This review discusses current progress on the development of chemical and biological approaches for the elimination of ARG carriers.

16.
Front Microbiol ; 11: 610296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33584574

RESUMO

In this paper we describe the transmission of a multi-drug resistant Klebsiella pneumoniae ST101 clone from hospital to wastewater and its persistence after chlorine treatment. Water samples from influents and effluents of the sewage tank of an infectious diseases hospital and clinical strains collected from the intra-hospital infections, during a period of 10 days prior to wastewater sampling were analyzed. Antibiotic resistant K. pneumoniae strains from wastewaters were recovered on selective media. Based on antibiotic susceptibility profiles and PCR analyses of antibiotic resistance (AR) genetic background, as well as whole-genome sequencing (Illumina MiSeq) and subsequent bioinformatic analyses, 11 ST101 K. pneumoniae strains isolated from hospital wastewater influent, wastewater effluent and clinical sector were identified as clonally related. The SNP and core genome analyses pointed out that five strains were found to be closely related (with ≤18 SNPs and identical cgMLST profile). The strains belonging to this clone harbored multiple acquired AR genes [bla CTX-M- 15, bla OXA- 48, bla OXA- 1, bla SHV- 106, bla TEM- 150, aac(3)-IIa, aac(6')-Ib-cr, oqxA10, oqxB17, fosA, catB3, dfrA14, tet(D)] and chromosomal mutations involved in AR (ΔmgrB, ΔompK35, amino acid substitutions in GyrA Ser83Tyr, Asp87Asn, ParC Ser80Tyr). Twenty-nine virulence genes involved in iron acquisition, biofilm and pili formation, adherence, and the type six secretion system - T6SS-III were identified. Our study proves the transmission of MDR K. pneumoniae from hospital to the hospital effluent and its persistence after the chlorine treatment, raising the risk of surface water contamination and further dissemination to different components of the trophic chain, including humans.

17.
PLoS One ; 15(1): e0228079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31999747

RESUMO

We report on the genomic characterization of 47 multi-drug resistant, carbapenem resistant and ESBL-producing K. pneumoniae isolates from the influent (I) and effluent (E) of three wastewater treatment plants (WWTPs) and from Romanian hospital units which are discharging the wastewater in the sampled WWTPs. The K. pneumoniae whole genome sequences were analyzed for antibiotic resistance genes (ARGs), virulence genes and sequence types (STs) in order to compare their distribution in C, I and E samples. Both clinical and environmental samples harbored prevalent and widely distributed ESBL genes, i.e. blaSHV, blaOXA, blaTEM and blaCTX M. The most prevalent carbapenemase genes were blaNDM-1, blaOXA-48 and blaKPC-2. They were found in all types of isolates, while blaOXA-162, a rare blaOXA-48 variant, was found exclusively in water samples. A higher diversity of carbapenemases genes was seen in wastewater isolates. The aminoglycoside modifying enzymes (AME) genes found in all types of samples were aac(6'), ant(2'')Ia, aph(3'), aaD, aac(3) and aph(6). Quinolone resistance gene qnrS1 and the multi-drug resistance oqxA/B pump gene were found in all samples, while qnrD and qnrB were associated to aquatic isolates. The antiseptics resistance gene qacEdelta1 was found in all samples, while qacE was detected exclusively in the clinical ones. Trimethroprim-sulfamethoxazole (dfrA, sul1 and sul2), tetracyclines (tetA and tetD) and fosfomycin (fosA6, known to be located on a transpozon) resistance genes were found in all samples, while for choramphenicol and macrolides some ARGs were detected in all samples (catA1 and catB3 / mphA), while other (catA2, cmIA5 and aac(6')Ib / mphE and msrE) only in wastewater samples. The rifampin resistance genes arr2 and 3 (both carried by class I integrons) were detected only in water samples. The highly prevalent ARGs preferentially associating with aquatic versus clinical samples could ascribe potential markers for the aquatic (blaSHV-145, qacEdelta1, sul1, aadA1, aadA2) and clinical (blaOXA-1, blaSHV-106,blaTEM-150, aac(3)Iia, dfrA14, oqxA10; oqxB17,catB3, tetD) reservoirs of AR. Moreover, some ARGs (oqxA10; blaSHV-145; blaSHV-100, aac(6')Il, aph(3')VI, armA, arr2, cmlA5, blaCMY-4, mphE, msrE, oqxB13, blaOXA-10) showing decreased prevalence in influent versus effluent wastewater samples could be used as markers for the efficiency of the WWTPs in eliminating AR bacteria and ARGs. The highest number of virulence genes (75) was recorded for the I samples, while for E and C samples it was reduced to half. The most prevalent belong to three functional groups: adherence (fim genes), iron acquisition (ent, fep, fyu, irp and ybt genes) and the secretion system (omp genes). However, none of the genes associated with hypervirulent K. pneumoniae have been found. A total of 14 STs were identified. The most prevalent clones were ST101, ST219 in clinical samples and ST258, ST395 in aquatic isolates. These STs were also the most frequently associated with integrons. ST45 and ST485 were exclusively associated with I samples, ST11, ST35, ST364 with E and ST1564 with C samples. The less frequent ST17 and ST307 aquatic isolates harbored blaOXA-162, which was co-expressed in our strains with blaCTX-M-15 and blaOXA-1.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Hospitais , Klebsiella pneumoniae/genética , Águas Residuárias/microbiologia , Purificação da Água , Sequenciamento Completo do Genoma , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Genes Bacterianos , Humanos , Integrons/genética , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Quinolonas/farmacologia , Romênia , Virulência/genética , beta-Lactamas/metabolismo
18.
Biomed Res Int ; 2019: 5712371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236408

RESUMO

BACKGROUND: Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) are among the most common infections worldwide, including Romania. To the best of our knowledge, this is the first study performed on a significant number of community-acquired (CA) UPEC strains isolated from Romanian outpatients, aiming to evaluate and establish potential correlations among the phylogenetic groups (PG), resistance profiles, and the virulence factors (VF) genes of the CA-UPEC isolates. MATERIALS/METHODS: The present study was performed on a total of 787 UPEC nonrepetitive isolates consecutively isolated during one month from outpatients with CA-UTIs, visiting one of the biggest laboratories in Bucharest, Romania, receiving patients from all over the country. The strains identification was performed by MALDI TOF and the susceptibility patterns were tested using Microscan according to CLSI guidelines. PCR assays were performed to detect the presence of different VFs (fimH gene encoding for type 1 fimbriae, afaBC for A fimbriae, sfaDE for S fimbriae, KpsMTII for capsule, hlyA for haemolysin A, hlyD for haemolysin D, and cnf-1 for tumor necrosis factor), the phylogenetic groups (PG) A, B1, B2, and D, and the extended spectrum beta-lactamases (ESBLs) genes. RESULTS: The 787 CA-UPEC strains were isolated predominantly from female patients (90.95%) of >30 years (~74%). The resistance rates were 47.52% for ampicillin, 41.16% for tetracycline, 24.39% for cotrimoxazole, 19.18% for amoxicillin-clavulanic acid, 15.50% for cefazolin, 14.99% for ciprofloxacin, and 14.86% for levofloxacin; 35.19% of the investigated strains were MDR and 9.03% ESBL producers (from which 42.25% were positive for blaCTX-M, 38.02% for blaTEM, and 19.71% for blaSHV). FimH was the most frequent virulence gene (93.90%) followed by hlyD (44.34%); afaBC (38.24%); KpsMTII (32.65%); sfaDE (23.88%); hlyA (12.45%); and cnf-1 (7.75%). The distribution of the analyzed UPEC strains in phylogenetic groups was different for non-MDR and MDR strains. Overall, 35% of the strains belonged to the phylogenetic group B2 (harboring the yjaA gene); 27% to group B1 (confirmed by the presence of the TspE4C2 fragment); 16% to group D; and 22% to group A. The CA-UPEC strains included in PG B1 and PG B2 proved to be the most virulent ones, the number of strains carrying multiple VFs (>3) being significantly larger as compared to strains belonging to PG A and PG D) (p<0,0001). The presence of one or two ESBL genes was significantly associated (p =0.0024) with PGs A and D. CONCLUSIONS: Our findings showed that the community UPEC strains circulating in Bucharest, Romania, belong predominantly to group B2 and >90% harbored the fimH gene. High MDR resistance rates were observed, as well as extended VF profiles, highlighting the importance of this type of studies for improving the epidemiological surveillance and the therapeutic or prophylactic management of the respective infections, in the context of antibiotic resistance emergence.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Filogenia , Infecções Urinárias/genética , Escherichia coli Uropatogênica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Ciprofloxacina/efeitos adversos , Ciprofloxacina/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Romênia/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/isolamento & purificação , Escherichia coli Uropatogênica/patogenicidade , Fatores de Virulência/genética , Adulto Jovem , beta-Lactamases/genética
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