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1.
bioRxiv ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617277

RESUMO

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTN∆C) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C-terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

2.
Cancers (Basel) ; 15(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37958315

RESUMO

Here, we investigate the correlation and statistical analyses between histological staging and molecular alterations in tumor-derived (tdDNA) and cell-free DNA (cfDNA) obtained from early-stage primary cutaneous melanoma (PCM) patients using digital PCR (dPCR) for the detection of the BRAF p.V600E somatic pathogenic variant. In the prospective study, a total of 68 plasma and paired tdDNA samples, and in the retrospective cohort, a total of 100 tdDNA samples were analyzed using dPCR and reverse hybridization StripAssay. The Breslow depth (BD) and Clark level were applied to categorize the study population. Our results demonstrate that dPCR is a highly sensitive and specific method for the detection of BRAF p.V600E somatic variants in cfDNA samples from PCM patients. A strong correlation was detected between BD and cfDNA concentration in all mutant and negative cases, between the tdDNA concentration and the tumor-derived variant allele frequency (VAF) of BRAF p.V600E, between the tdVAF and the cfVAF in all cases, and between the cfDNA and cfVAF in mutant cases. The tdVAF and cfVAF of BRAF p.V600E and cfDNA concentration were the highest in Clark's V category. The cfDNA concentration was statistically significantly higher in Clark's III, IV, and V groups compared to cases with a better prognosis. It can also be explained by the fact that cases with a more advanced stage classification release more cfDNA into the peripheral circulation.

3.
Cancers (Basel) ; 15(3)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36765856

RESUMO

BCOR (BCL6 corepressor)-rearranged sarcomas (BRSs) are a heterogeneous group of sarcomas previously classified as part of the group of "atypical Ewing" or "Ewing-like" sarcomas, without the prototypical ESWR1 gene translocation. Due to their similar morphology and histopathological features, diagnosis is challenging. The most common genetic aberrations are BCOR-CCNB3 fusion and BCOR internal tandem duplication (ITD). Recently, various new fusion partners of BCOR have been documented, such as MAML3, ZC3H7B, RGAG1, and KMT2D, further increasing the complexity of such tumor entities, although the molecular pathogenetic mechanism remains to be elucidated. Here, we present an index case of intrathoracic BRS that carried a novel BCOR-CLGN (calmegin) gene fusion, exhibited by a 52-year-old female diagnosed initially by immunohistochemistry due to the positivity of a BCOR stain; the fusion was identified by next-generation sequencing and was confirmed by Sanger sequencing. In silico protein analysis was performed to demonstrate the 3D structure of the chimera protein. The physicochemical properties of the fusion protein sequence were calculated using the ProtParam web-server tool. Our finding further broadens the fusion partner gene spectrum of BRS. Due to the heterogeneity, molecular ancillary tests serve as powerful tools to discover these unusual variants, and an in silico analysis of the fusion protein offers an appropriate approach toward understanding the exact pathogenesis of such a rare variant.

4.
Sci Adv ; 9(4): eadd7474, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36696507

RESUMO

Innovative approaches to prevent catheter-associated urinary tract infections (CAUTIs) are urgently required. Here, we describe the discovery of an acrylate copolymer capable of resisting single- and multispecies bacterial biofilm formation, swarming, encrustation, and host protein deposition, which are major challenges associated with preventing CAUTIs. After screening ~400 acrylate polymers, poly(tert-butyl cyclohexyl acrylate) was selected for its biofilm- and encrustation-resistant properties. When combined with the swarming inhibitory poly(2-hydroxy-3-phenoxypropyl acrylate), the copolymer retained the bioinstructive properties of the respective homopolymers when challenged with Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Urinary tract catheterization causes the release of host proteins that are exploited by pathogens to colonize catheters. After preconditioning the copolymer with urine collected from patients before and after catheterization, reduced host fibrinogen deposition was observed, and resistance to diverse uropathogens was maintained. These data highlight the potential of the copolymer as a urinary catheter coating for preventing CAUTIs.


Assuntos
Polímeros , Infecções Urinárias , Humanos , Cateterismo Urinário , Biofilmes , Cateteres Urinários/microbiologia , Infecções Urinárias/prevenção & controle , Infecções Urinárias/microbiologia , Bactérias , Escherichia coli
5.
Pathogens ; 11(11)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36422606

RESUMO

Background: Streptococcus agalactiae (Group B Streptococcus, GBS) is the most common cause of serious infections in the first 3 months of life worldwide. The pathogenicity of GBS is closely related to serotypes, surface proteins and virulence factors, and the distribution of them may vary temporally and geographically. However, data related to GBS surface proteins and virulence determinants in China are very few. The aim of this study is to investigate the genetic characteristics of clinical GBS isolates from infected infants. Methods: We recovered GBS isolates from infected infants younger than 3 months during 2017−2021 at Maternal and Child Health Hospital of Hubei Province in China. We assessed the GBS serotypes, surface proteins, virulence determinants and antibiotic resistance genes distribution, by Multilocus sequence typing (MLST) and whole-genome sequencing analysis. Results: Among 97 isolates (81 EOD and 16 LOD), 5 serotypes were detected. Serotype III was the most represented (49.5%), followed by type Ib (20.6%). The isolates belonged to 17 different sequence types (STs) that grouped into the 8 clonal complexes (CCs). The most frequently identified ST was ST17 (23.7%). The most predominant surface protein of alpha-protein-like (alp) family (one of the protein components of the GBS surface antigen, resistant to trypsin) present was Rib (41.2%), which was mainly detected in serotype III. The srr1, which encodes Srr1 protein, was identified in 54.6% of isolates. The hvgA encoding for hypervirulent GBS adhesin can be detected in all 24 serotype III GBS. Among the pilus islands genes, 50% and 58.8% of the isolates were positive for pi-1 and pi-2a genes, respectively. The presence of pi-2b was mainly associated with serotype III/CC17 strains; 56.7% of isolates carried tetM, tetO/tetL, ermB antibiotic resistant genes. Among all the virulence genes detected, the cfb-cylE-lmb-pavA pattern was the main virulence gene profile (81.4%), mainly in serotype III/CC17. Conclusions: The whole genomic sequencing data revealed the high variation in surface proteins, determining virulence and antibiotic resistance in clinical isolates from 97 GBS infected infants. These data provide insightful characteristics of genetic features of GBS. Constant epidemiological surveillance is warranted to provide information on the GBS pathogenic dynamics and antibiotic resistance profiles in the surveyed areas for improving therapeutic outcomes.

6.
Cancers (Basel) ; 14(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36428747

RESUMO

PURPOSE: Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies, with less than 10% of patients surviving more than 5 years. Existing biomarkers for reliable survival rate prediction need to be enhanced. As a result, the objective of this study was to create a novel immune-related gene prognostic index (IRGPI) for estimating overall survival (OS) and to analyze the molecular subtypes based on this index. Materials and procedures: RNA sequencing and clinical data were retrieved from publicly available sources and analyzed using several R software packages. A unique IRGPI and optimum risk model were developed using a machine learning algorithm. The prediction capability of our model was then compared to that of previously proposed models. A correlation study was also conducted between the immunological tumor microenvironment, risk groups, and IRGPI genes. Furthermore, we classified PAAD into different molecular subtypes based on the expression of IRGPI genes and investigated their features in tumor immunology using the K-means clustering technique. RESULTS: A 12-gene IRGPI (FYN, MET, LRSAM1, PSPN, ERAP2, S100A1, IL20RB, MAP3K14, SEMA6C, PRKCG, CXCL11, and GH1) was established, and verified along with a risk model. OS prediction by our model outperformed previous gene signatures. According to the findings of our correlation studies, different risk groups and IRGPI genes were found to be tightly related to tumor microenvironments, and PAAD could be further subdivided into immunologically distinct molecular subtypes based on the expression of IRGPI genes. CONCLUSION: The current study constructed and verified a unique IRGPI. Furthermore, our findings revealed a connection between the IRGPI and the immunological microenvironment of tumors. PAAD was differentiated into several molecular subtypes that might react differently to immunotherapy. These findings could provide new insights for precision and translational medicine for more innovative immunotherapy strategies.

7.
Microbiol Resour Announc ; 11(9): e0044822, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35997498

RESUMO

We report the draft genome sequence of the laboratory strain Staphylococcus aureus NCTC 6571-UB, a strain that was derived from S. aureus NCTC 6571. This strain was selected for sequencing in order to provide information on the genome dynamics and the acquired resistance genes for penicillin G, trimethoprim, and sulfamethoxazole resistance.

8.
Microbiol Resour Announc ; 11(9): e0064622, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35993720

RESUMO

We report the draft genome sequence and antibiotic susceptibility of Pseudomonas aeruginosa strain PAO1-UB, a subline of the common reference strain PAO1. This strain was sequenced in order to provide information on the genome dynamics of PAO1 sublines and their genes conferring resistance to multiple antibiotics.

9.
Pathol Oncol Res ; 28: 1610498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979530

RESUMO

Anastomosing haemangioma (AH) is a newly described distinct vascular neoplasm that histologically may confuse with well-differentiated angiosarcoma (AS) for those who are unfamiliar with this rare entity. We aimed to identify molecular genetic differences between AHs and ASs by carrying out immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Immunohistochemically, all six cases showed positivity for cyclinD1 and pERK. All cases of AH showed focal weak positive reaction for p53 and MIB-1, and the IHCs for HIF-1α were all negative for all three cases. Those three cases of angiosarcoma revealed strong, diffuse positivity for p53, 50%-70% MIB-1 labelling, and multifocal, moderate to strong HIF-1α expression. To further clarify the difference in p53 expression, we carried out a FISH which revealed 17p polysomy in all three ASs whereas copy number aberration was absent in the AH group. In one AH case, the GNA11 c.627G > T nucleotide variant was detected. Due to the rarity and overlapping morphological features, AH might be difficult to separate from other vascular tumours, in particular from well-differentiated AS also featured by mild hyperchromatic, hobnail-like endothelial cells. The potential molecular differences between these two entities presented here may be used in support of the correct diagnosis.


Assuntos
Hemangioma , Hemangiossarcoma , Células Endoteliais/patologia , Hemangioma/genética , Hemangioma/patologia , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Humanos , Hibridização in Situ Fluorescente , Proteína Supressora de Tumor p53/genética
10.
BMC Res Notes ; 15(1): 107, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35303951

RESUMO

OBJECTIVE: The naked mole rats (NMRs, Heterocephalus glaber) are subterranean rodents that belong to the family Bathyergidae. They gained the attention of the scientific community for their exceptionally long lifespan of up to 30 years and have become an animal model of biomedical research on neurodegenerative diseases, aging and cancer. NMRs dig and survive in a maze of underground tunnels and chambers and demarcate toilet chambers for defecation and urination. Due to their coprophagic behaviours, we believed that the toilet chamber might play a role in maintaining optimal health of the NMRs. A 16S rRNA gene amplicon sequencing was performed to characterize the bacterial microbiome of faecal samples collected from the toilet chamber of a laboratory NMR colony. RESULTS: Four faecal samples were collected at different time points from the same toilet chamber of a laboratory NMR colony for analysis. The 16S rRNA gene amplicon sequencing revealed that bacterial phyla Firmicutes and Bacteroidetes were the dominant taxa in the bacterial microbiome of NMRs. The relative abundance of the bacterial taxa shifted substantially between time points, indicating a dynamic microbiome in the toilet chamber. The data provided an insight to the faecal microbiome of NMRs in the toilet chamber.


Assuntos
Aparelho Sanitário , Microbiota , Animais , Modelos Animais de Doenças , Ratos-Toupeira/genética , RNA Ribossômico 16S/genética
11.
Front Cell Infect Microbiol ; 11: 651968, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34109134

RESUMO

Maternal vaginal/rectal colonization of group B streptococcus (GBS) is a main risk for neonatal invasive infection. Efficient determination of GBS colonization in pregnant women is crucial. This study aimed to investigate the prevalence of GBS carriage and evaluate the diagnostic performance of six methodologies for GBS screening conducted in China, including blood agar plate, liquid chromogenic medium, and loop-mediated isothermal amplification (LAMP) without pre-enrichment, chromogenic agar plate with pre-enrichment, and GBS antigen detection without and with pre-enrichment in comparison with the standard reference method (Lim broth-enriched subculture with plating on 5% sheep blood agar). Vaginal/rectal swabs were collected from 1,281 pregnant women at 35-37 weeks of gestation. Of them, 309 were taken in triplicate, one for Lim broth-enriched subculture, one for blood agar plate, and the third for GBS antigen detection (Reagent W); 177 were acquired in duplicate, one for Lim broth-enriched subculture and the other for GBS antigen detection (Reagent H); 502 were obtained in duplicate, one for Lim broth-enriched subculture and the other for liquid chromogenic medium; 158 were collected in duplicate, one for Lim broth-enriched subculture and the other for LAMP; and 135 were inoculated in Lim broth-enriched for GBS antigen detection (Reagent W) and subculture with chromogenic agar plate and 5% blood agar plate. The overall prevalence of GBS carriage was 10.1% (130/1,281, 95% CI: 8.5-12.1%) according to the standard reference method. Compared with the standard reference method, the LAMP had excellent performance of sensitivity (100%, 95%CI: 83.4-100%), specificity (94%, 95%CI: 88.1-97.1%), and Yoden index (0.940); as well as the blood agar plate with sensitivity (81.5%, 95%CI: 61.3-93.0%), specificity (100%, 95%CI: 98.3-100.0%), and Yoden index (0.815). The other four methods were not sufficient to reach the threshold in terms of sensitivity or specificity compared to the standard reference method. Furthermore, for LAMP, results can be obtained within 0.5-1 h, while for blood agar plate, which needed 24-48 h, and further identification was required. Our data suggested that the performance of LAMP was highly comparable to the standard Lim broth-enriched subculture and LAMP is considered as an alternative for fast and accurate GBS screening.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , China , Meios de Cultura , Feminino , Humanos , Recém-Nascido , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Gravidez , Gestantes , Sensibilidade e Especificidade , Streptococcus agalactiae , Vagina
12.
Diagnostics (Basel) ; 11(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535453

RESUMO

Merkel cell carcinoma (MCC) is a rare, high-grade, aggressive cutaneous neuroendocrine malignancy most commonly associated with sun-exposed areas of older individuals. A relatively newly identified human virus, the Merkel cell polyomavirus (MCPyV) has been implicated in the pathogenesis of MCC. Our study aimed to examine nine MCC cases and randomly selected 60 melanoma cases to identify MCPyV status and to elucidate genetic differences between virus-positive and -negative cases. Altogether, seven MCPyV-positive MCC samples and four melanoma samples were analyzed. In MCPyV-positive MCC RB1, TP53, FBXW7, CTNNB1, and HNF1A pathogenic variants were identified, while in virus-negative cases only benign variants were found. In MCPyV-positive melanoma cases, besides BRAF mutations the following genes were also affected: PIK3CA, STK11, CDKN2A, SMAD4, and APC. In contrast to studies found in the literature, a higher tumor burden was detected in virus-associated MCC compared to MCPyV-negative cases. No association was identified between virus infection and tumor burden in melanoma samples. We concluded that analyzing the key morphologic and immunohistological features of MCC is critical to avoid confusion with other cutaneous malignancies. Molecular genetic investigations such as next-generation sequencing (NGS) enable molecular stratification, which may have future clinical impact.

13.
Diagnostics (Basel) ; 11(1)2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33375764

RESUMO

Retinoblastoma (Rb) is a malignant tumor of the developing retina that affects children before the age of five years in association with inherited or early germline mutations of the RB1 gene. The genetic predisposition is also a driver for other primary malignancies, which have become the leading cause of death in retinoblastoma survivors. Other malignancies can occur as a consequence of radiotherapy. We describe a patient with retinoblastoma in which we detected a novel RB1 c.2548C > T, p.(Gln850Ter) and a synchronous MET c.3029C > T, p.(Thr1010Ile) mutation as well. After presenting with bilateral retinoblastoma, the patient developed at least four different manifestations of two independent osteosarcomas. Our goal was to identify all germline and somatic genetic alterations in available tissue samples from different time periods and to reconstruct their clonal relations using next generation sequencing (NGS). We also used structural and functional prediction of the mutant RB and MET proteins to find interactions between the defected proteins with potential causative role in the development of this unique form of retinoblastoma. Both histopathology and NGS findings supported the independent nature of a chondroblastic osteosarcoma of the irradiated facial bone followed by an osteoblastic sarcoma of the leg (tibia).

15.
Front Microbiol ; 11: 609526, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33569045

RESUMO

Fluoroquinolone (FQ)-resistant Group B Streptococcus (GBS) has been reported with considerable cross-resistance, worsening the crisis of multidrug-resistant (MDR) GBS in clinical settings. However, national epidemiological data on FQ-resistant GBS in mainland China have not been well-characterized. This study aimed to determine the prevalence of FQ resistance among GBS from neonatal invasive infections and maternal colonization in northern and southern China, to investigate the serotyping, multilocus sequence typing, and antibiotic cross-resistance, and to characterize the mutations in gyrA and parC genes in quinolone resistance-determining region (QRDR). In order to provide a comprehensive view of the location and structure of resistance genes, whole-genome sequencing on III/ST19 MDR isolates were performed. Among 426 GBS, 138 (32.4%) were FQ resistant, with higher prevalence in northern China than in southern China in both neonates (57.8%, 37/64 vs. 21.7%, 39/180) and pregnant women (50.9%, 29/57 vs. 26.4%, 33/125). Serotypes were distributed as III (48.5%), Ib (39.9%), V (6.5%), and Ia (5.1%). Sequence types were mainly ST19 (53.6%) and ST10 (39.1%), followed by ST12 (1.4%), ST17 (1.4%), ST23 (1.4%), and 0.7% each of ST27, ST188, ST197, and ST597. ST19 isolates were more prevalent in southern China than in northern China in both neonates (64.1%, 25/39 vs. 27.0%, 10/37) and pregnant women (81.8%, 27/33 vs. 41.4%, 12/29), whereas ST10 isolates were more common in northern China than in southern China in both neonates (64.9%, 24/37 vs. 20.5%, 8/39) and pregnant women (58.6%, 17/29 vs. 15.2%, 5/33). Serotype III isolates were mainly ST19 (89.6%, 60/67), while Ib isolates were largely ST10 (94.5%, 52/55). Sequencing data revealed several mutations in QRDR, including Ser81Leu in gyrA (99.2%, 130/131), Ser79Phe or Tyr in parC (76.2%, 48/63), and a previously unreported Ile218Thr and Ile219Phe double mutation pattern (49.2%, 31/63) in parC. ST10 isolates were associated with Ser79Phe (84%, 21/25), while ST19 isolates were limited to Ser79Tyr (95.7%, 22/23). A new integrative and conjugative element (ICE) harboring tetM and gyrA genes was identified in a III/ST19 isolate. This study investigates the molecular characteristics of FQ-resistant GBS in northern and southern China, emphasizing the need for continuous surveillance geographically and further research to characterize the mechanisms of ICE transfer.

16.
Front Cell Infect Microbiol ; 10: 577031, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33585264

RESUMO

Group B Streptococcus (GBS) is an important etiological agent of maternal and neonatal infections as well as postpartum women and individuals with impaired immunity. We developed and evaluated a rapid classification method for sequence types (STs) of GBS based on statistic models with Matrix-Assisted Laser Desorption/Ionization Time-of Flight Mass Spectrometry (MALDI-TOF/MS). Whole-cell lysates MALDI-TOF/MS analysis was performed on 235 well-characterized GBS isolates from neonatal invasive infections in a multi-center study in China between 2015 and 2017. Mass spectra belonging to major STs (ST10, ST12, ST17, ST19, ST23) were selected for model generation and validation. Recognition and cross validation values were calculated by Genetic Algorithm-K Nearest Neighbor (GA-KNN), Supervised Neural Network (SNN), QuickClassifier (QC) to select models with the best performance for validation of diagnostic efficiency. Informative peaks were further screened through peak statistical analysis, ST subtyping MSP peak data and mass spectrum visualization. For major STs, the ML models generated by GA-KNN algorithms attained highest cross validation values in comparison to SNN and QC algorithms. GA-KNN models of ST10, ST17, and ST12/ST19 had good diagnostic efficiency, with high sensitivity (95-100%), specificity (91.46%-99.23%), accuracy (92.79-99.29%), positive prediction value (PPV, 80%-92.68%), negative prediction value (NPV, 94.32%-99.23%). Peak markers were firstly identified for ST10 (m/z 6250, 3125, 6891) and ST17 strains (m/z 2956, 5912, 7735, 5218). Statistical models for rapid GBS ST subtyping using MALDI-TOF/MS spectrometry contributes to easier epidemical molecular monitoring of GBS infection diseases.


Assuntos
Infecções Estreptocócicas , Streptococcus agalactiae , China , Feminino , Humanos , Recém-Nascido , Modelos Estatísticos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/genética
17.
Infect Drug Resist ; 12: 3797-3805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819560

RESUMO

BACKGROUND: Neonatal sepsis (NS) is one of the leading causes of infant morbidity and mortality, but little is known about pathogen incidence and distribution in China. METHODS: In this retrospective study (January 2012 to December 2016), culture-proven cases aged less than 28 days with diagnosed NS in the Guangzhou Women and Children's Medical Center, South China, were analyzed for pathogen incidence and antimicrobial resistance. RESULTS: A total of 620 isolates were identified from 597 NS cases. Gram-negative bacteria (n=371, 59.8%) dominated over Gram-positive bacteria (n=218, 35.2%) and fungi (n=30, 4.8%). Klebsiella pneumoniae (21.9%), Escherichia coli (21.9%), group B Streptococcus (GBS, 13.2%), and Staphylococcus aureus (6.8%) were the four most predominant pathogens. In early-onset sepsis (EOS), GBS (30.0%) and E. coli (20.0%) were dominant, whereas in late-onset sepsis (LOS), K. pneumoniae (25.6%) and E. coli (22.4%) were dominant. E. coli (25.2%) and GBS (17.7%) were the most frequently isolated from term patients, whereas K. pneumoniae was the most frequently isolated from preterm patients (34.9%). Of the infected infants, 9.5% died from sepsis, most commonly by E. coli infection (16.2%). Among 91,215 live births (LBs) delivered in the study hospital (2012-2016), 252 infants developed sepsis infection (2.76 per 1000 LBs, 95% CI 2.4-3.1), including EOS (0.78 per 1000 LBs) and LOS (2.13 per 1000 LBs). All GBS isolates were susceptible to ß-lactam antibiotics, and S. aureus, including methicillin-resistant isolates, were susceptible to vancomycin. An extended-spectrum ß-lactamase producer was identified in 37.3% of E. coli and 50.4% of K. pneumoniae. CONCLUSION: K. pneumoniae was the most frequent pathogen in culture-proven NS in South China, primarily associated with LOS in preterm, whereas GBS was the dominant pathogen in EOS. E. coli was common in both episodes with the highest mortality.

18.
BMC Infect Dis ; 19(1): 812, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533652

RESUMO

BACKGROUND: Invasive group B Streptococcus (GBS) disease in Chinese infants has gradually gained attention in recent years, but the molecular epidemiology of the pathogen is still not well known. METHODS: This multicenter study retrospectively investigated distribution of capsular serotypes, sequence types (STs), and hypervirulent GBS adhesin gene (hvgA) in clinical GBS isolates that caused invasive disease in infants aged < 3 months of age in southern mainland China between January 2013 and June 2016. Genes for antibiotic resistance to tetracycline, erythromycin, and clindamycin were also examined. RESULTS: From a total of 93 GBS isolates taken from 34 early-onset disease (EOD, 0-6 days after birth) and 59 late-onset disease (LOD, 7-89 days after birth) cases, four serotypes were identified: serotypes III (79.6%), Ib (12.9%), Ia (4.3%), and V (3.2%). Serotype III accounted for 73.5% of EOD and 83.1% of LOD and was responsible for 75.5% of cases involving meningitis. Fifteen STs were found, with the majority being ST17 (61.3%), ST12 (7.5%), ST19 (7.5%), and others (23.7%). 96.8% of STs belonged to only five clonal complexes (CCs): CC17 (64.5%), CC10 (12.9%), CC19 (9.7%), CC23 (6.5%), and CC1 (3.2%). The hvgA gene was detected in 66.7% of GBS isolates and 95% of CC17 isolates, all of which were serotype III except one serotype Ib/CC17 isolate. A large proportion of GBS isolates were found to be resistant to tetracycline (93.5%), clindamycin (65.5%), and erythromycin (60.2%). Genes of tetO (74.7%) and tetM (46.0%) were found in tetracycline resistant isolates, linB (24.6%) in clindamycin resistant isolates, and ermB (87.5%) and mefA (3.6%) in erythromycin resistant isolates. CONCLUSION: Our results reveal higher prevalence of serotype III, ST17, CC17, hvgA expressing, and antibiotic resistant GBS isolates than previously reported in southern mainland China. This study provides guidance for appropriate measures of prevention and control to be taken in the future.


Assuntos
Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Adesinas Bacterianas/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Tipagem de Sequências Multilocus , Prevalência , Estudos Retrospectivos , Sorogrupo , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/patologia , Streptococcus agalactiae/genética
19.
Chem Commun (Camb) ; 55(66): 9765-9768, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31355394

RESUMO

Bacterial quorum sensing has been implicated in a number of pathogenic bacterial processes, such as biofilm formation, making it a crucial target for developing materials with a novel antibiotic mode of action. This paper describes poly(N-isopropyl acrylamide) that has been covalently linked, at multiple chain ends, to homoserine lactone to give a highly branched polymer functionalized with a key messenger molecule implicated in QS. This novel functional material has shown promising anti-QS activity in a Chromobacterium violaceum assay.


Assuntos
Acrilamidas/farmacologia , Chromobacterium/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Chromobacterium/fisiologia
20.
Infect Drug Resist ; 11: 2561-2569, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30573985

RESUMO

BACKGROUND: A multidrug-resistant (MDR) RR2 gene cluster was identified by whole-genome sequencing in several highly virulent (ST-17) Group B streptococcus (GBS) isolates, which caused neonatal invasive infections in southern China in 2016. Tracing the transmission and distribution of MDR isolates in this area is important for the effective management of future infections. The aim of this study was to obtain longitudinal data of MDR isolates to monitor epidemiological trends of general common isolates in southern China, and provide evidence for future characterization of antimicrobial resistance mechanisms. METHODS: Clinical information and antimicrobial susceptibility of GBS isolates were acquired from electronic information management system databases of the hospital under study between January 2011 and December 2017. To confirm the presence of intact RR2, the tetO, ant6, lnuB, and ant9 genes located upstream, midstream, and downstream of RR2 were detected by PCR and DNA sequencing. RESULTS: A total of 149 cases of neonatal invasive GBS infection were identified during the period 2011-2017. Among them, 119 cases (79.9%) were caused by MDR isolates, with a general increasing trend over the past 7 years. Further characterization of 11 isolates showed that six isolates causing late-onset disease (LOD) carry the tetO, ant6, and lnuB genes, which are located on RR2. Moreover, lnuB and ant9 consistently co-occurred in GBS isolates, which suggests their close proximity to one another in the RR2 gene cluster. CONCLUSION: The MDR GBS is responsible for a large number of neonatal invasive infections and occurs with increasing frequency over time. Particularly, the MDR GBS isolates that cause LOD are more likely to carry the RR2 gene cluster, compared with those that cause early-onset disease. The rise in number of MDR GBS isolates emphasizes the pressing need for continuous surveillance to monitor their antibiotic susceptibility and epidemiology.

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