The aim of this research is twofold: 1) to shed light on zika's binding and entry mechanism while 2) demonstrating the effectiveness of our magnetic relaxation platform to achieve this goal. Magnetic ...relaxation-sensitive nanoparticles (MRNPs) are used in a novel fashion to analyze binding interactions between the zika envelope protein (ZENV) and proposed host cell receptors: AXL, HSP70, and TIM-1. Computational analysis is also utilized to examine these binding interactions for the first time. In addition, the role of crizotinib as a potential binding inhibitor is demonstrated and the possibility of ligand-independent phosphatidylserine-mediated binding is explored. Our findings suggest that while the extracellular domain of AXL has the highest affinity for ZENV; HSP70, TIM-1, and phosphatidylserine might also play active roles in zika tropism, which offers a potential explanation for the variety of zika-associated symptoms. This is, to our knowledge, the first time that MRNPs have been used to examine and quantify host-zika interactions. Our magnetic relaxation platform allows for timely and sensitive analysis of these intricate binding relationships, and it is easily customizable for further examination of additional host-pathogen interactions.
Enterococci, though they are a part of commensal flora, are becoming increasingly important as nosocomial pathogens, due to their inherited and acquired resistances to several antimicrobial agents. ...In this context, Enterococcus faecium (E.faecium) requires a special mention due to its characteristic of Multidrug Resistance (MDR) and its ability to disseminate.
This study was undertaken to phenotypically characterize and determine clonal relatedness amongst the indoor isolates of Enterococcus faecium (E. faecium) which were isolated from patients with urinary tract infections (UTIs).
This study was carried out prospectively in a tertiary care university hospital and in Department of Microbiology, Varanasi, India.
Urine samples were collected from patients who were admitted in different departments of the hospital with a clinical diagnosis of UTIs and they were processed for a period of one year. Enterococcal species were identified by doing extensive biochemical tests. Anti-microbial susceptibility testing was done by disc diffusion and agar dilution methods. Molecular typing of the isolates was done by Random Amplified Polymorphic DNA (RAPD) typing method.
A total of 48 Enterococcal urinary isolates were identified in indoor patients, among which a majority (46, 95.83%) were E.faecium isolates. These isolates exhibited high resistance to fluoroquinolones (91.3%) and to ampicillin (60.86%) in particular. Two isolates were found to be resistant to vancomycin on screen agar. RAPD typing showed two major clusters, one of which had ten strains of 100% similarity, all of which were isolated from a common source.
This study showed dissemination of multidrug resistant E. faecium isolates within the hospital. Being a quick and cost effective method, RAPD typing can be used to show clonal relatedness and to trace possible sources of organisms for epidemiological purposes.
Not only has it spread rapidly to other countries, but there are more data evidencing causal relationships to neurological disorders in unborn children with infected mothers, as well as more recent ...evidence supporting a link between ZIKV and neurological disorders in adults 5. Because it is mainly asymptomatic and because of the grave consequences this can have on developing fetuses, the virus has come under global investigation, with the World Health Organization (WHO) officially declaring ZIKV a Public Health Emergency of International Concern (PHEIC) in 2016 6. According to WHO, by March 2017, 23 countries or territories had reported an increase in GBS cases, suggesting a causal link to ZIKV, and 31 had reported increases in central nervous system malformations, with preliminary evidence associating this with ZIKV infection 9. RT-PCRs have been considered the accepted standard for viral molecular detection due to high selectivity and fairly high sensitivity, but PCR platforms require multi-temperature heating of samples for denaturation, annealing, and extension 11, as well as an additional incubation step for a total reaction time of 2 hours 8. According to the WHO vaccine pipeline tracker, there are currently 12 active vaccine candidates in trial, with 2 of those having proceeded to phase II.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The rapid emergence of drug resistance in Acinetobacter baumannii has put forward the use of colistin as a last-resort treatment for infections with A. baumannii. Empirical colistin use without prior ...susceptibility testing has been one of the factors that has been promoting drug resistance in low-resource settings. In this regard, while the advocated broth microdilution (BMD) method for colistin susceptibility testing is often considered cumbersome, the preferable colistin broth disk elution (CBDE) method has not yet been approved for A. baumannii. To prevent the underreporting of colistin susceptibility, we tested the CBDE method for A. baumannii and compared the results with those of BMD. A total of 125 A. baumannii, including 100 susceptible and 25 resistant isolates were tested via the CBDE method and compared with the standard BMD method. The essential agreement, categorical agreement, sensitivity, and specificity for CBDE were 97.6% (
= 122), 98.4% (
= 123), 100%, and 98.40%, respectively. The percentage of major error found was 1.6% (
= 2), and no very major error was found. CBDE in A. baumannii could be considered in low-resource settings.
The relatively cumbersome broth microdilution (BMD) method for routine colistin susceptibility testing has not been adopted, especially in low-resource settings, often leading to the underreporting of colistin susceptibility and the promotion of the empirical use of colistin. In this regard, the much-preferred colistin broth disk elution (CBDE) method has not yet been approved for A. baumannii. We evaluated colistin susceptibility via the CBDE method, compared the results with those of the BMD method in 125 A. baumannii isolates with various profiles, and inferred that the CBDE method using 50 μL inoculum could be helpful, at least in resource-limited setups, versus not reporting susceptibility testing for colistin.
The recent emergence of multidrug-resistant (MDR)
with hypervirulent traits causing severe infections and considerable mortality is a global cause for concern. The challenges posed by these ...hypermucoviscous strains of
with regard to their optimal treatment, management, and control policies are yet to be answered. We studied a series of extensively drug-resistant (XDR) and hypervirulent
with resistance to carbapenems and polymyxins causing neonatal sepsis in a tertiary care hospital in India. A total of 9
isolates from 9 cases of neonatal sepsis were studied with respect to their clinical relevance, antimicrobial susceptibility profile, presence of extended spectrum β lactamase (ESBL) production, and responsible genes, carbapenemases (classes A, B, and D), and aminoglycoside-resistant genes. Hypervirulence genes encoding hypermucoid nature, iron uptake, and siderophores were detected by multiplex PCR. The plasmid profile was studied by replicon typing. Isolates were typed by multilocus sequence typing (MLST) and enterobacterial repetitive intergenic consensus (ERIC) PCR to study the sequence types (STs) and clonal relation, respectively. The neonates in the studied cases had history of pre-maturity or low birth weight with maternal complications. All the cases were empirically treated with piperacillin-tazobactam and amikacin followed by imipenem/meropenem and vancomycin and polymyxin B as a last resort. However, all the neonates finally succumbed to the condition (100%). The studied isolates were XDR including resistance to polymyxins harboring multiple ESBL genes and carbapenemase genes (
and
). Hypervirulence genes were present in various combinations with
genes present in all the isolates. IncFI plasmids were detected in these isolates. All belonged to ST5235. In ERIC PCR, 6 different clusters were seen. The study highlighted the emergence and burden of XDR hypervirulent isolates of
causing neonatal sepsis in a tertiary care hospital.
Abstract
Objective
Coagulase-negative staphylococci (CoNS) are being implicated as one of the leading causes of bloodstream infection (BSI). To study the spectrum, prevalence, and antimicrobial ...susceptibility of CoNS causing BSI in neonates.
Materials and Methods
A cross-sectional study was done in level III neonatal intensive care unit (NICU). Blood samples in automated culture bottles were processed as per the standard technique. Previously validated methods were followed for the characterization of CoNS and for AST of standard antibiotics by Kirby Bauer disk diffusion and vancomycin by agar dilution. The prevalence of causative organisms and susceptibility of CoNS were statistically analyzed. Categorical variables were compared by chi-square or Fisher's exact probability tests.
Result
In total, 1,365 blood samples (1,365 neonates) were studied, of which 383 (28.05%) were positive and 982 (71.94%) were negative. Gram-positive organisms (GPC) predominated (
n
= 238; 62.14%) (
p
< 0.001) with 41.77% (160/383)
S. aureus
and 13.83% (53/383) CoNS. CoNS included
S. epidermidis
(19, 38%),
S
.
haemolyticus
(7, 14%),
S. hominis
(6, 12%),
S. simulans
(6,12%),
S. capitis
(5,10%),
S. cohnii
(4, 8%),
S. warneri
(1, 2%), and
S. xylosus
(1, 2%). The susceptibility to netilmicin, linezolid, and vancomycin was 100% (
p
≤ 0.001), and 54% (
n
= 27) had vancomycin MIC of 0.125 μg/mL but methicillin-resistant CoNS (MRCoNS) was 70%. Methicillin-susceptible (MS) CoNS had lower MIC of vancomycin (
p
< 0.05) than MRCoNS.
Conclusion
The spectrum of pathogens causing BSI in neonates is changing with predominance of GPC and among CoNS,
S. epidermidis
. Considerable proportion of MRCoNS with the emergence of MIC creep for vancomycin requires immediate attention.
Drug resistance in tuberculosis is a major public health challenge in developing countries. The limited data available on drug resistance in extra pulmonary tuberculosis stimulated us to design our ...study on anti-tuberculosis drug resistance pattern in cases of extra pulmonary tuberculosis in a tertiary referral hospital of North India. We performed Geno Type MTBDRplus assay in comparison with conventional drug susceptibility testing by proportion method to study the mutation patterns in rpoB, katG and inhA genes.
A total of 510 extra pulmonary samples were included in this study. After the smear microscopy, all the specimens were subjected for culture on Lowenstein Jensen (LJ) media. Phenotypic drug susceptibility testing (DST) was performed on LJ media for all the MTB isolates and compared with the results of Geno Type MTBDRplus assay which was performed with the DNA isolated from the culture by conventional method.
Of 510 specimens cultured, the total culture positivity obtained was 11.8% (60) encompassing 54 (10.6%) Mycobacterium tuberculosis and 6 (1.2%) non-tubercular mycobacteria (NTM). DST results by Geno Type MTBDRplus assay and solid culture methods were compared in 51 MTB isolates excluding the two Rif indeterminate and one invalid test. Geno Type MTBDRplus accurately identified 13 of 14 rifampicin-resistant strains, 14 of 15 isoniazid-resistant strains and 13 of 14 as multi drug resistant tuberculosis (MDR-TB) in comparison with conventional method. Sensitivity and specificity were 92.86% and 97.30% respectively for detection of RIF resistance, 93.33% and 94.44% respectively for detection of INH resistance, 92.86% and 97.30% respectively for detection of MDR-TB, while the overall concordance of Geno Type MTBDRplus assay with conventional DST was 94.11%. The turn-around time for performing Geno Type MTBDRplus assay test was 48 hours.
The problem of MDR in extra pulmonary tuberculosis (EPTB) cannot be overlooked and due attention on patients should be given. Routine use of Geno Type MTBDRplus assay for the diagnosis of MDR-EPTB can substantially reduce the time between diagnosis and drug therapy. Culture along with Geno Type MTBDRplus assay could be a solution for rapid and accurate diagnosis of MDR-TB in low bacillary non sputum specimens.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study reports the polyphenol profile of helencha (
Enydra fluctuans
Lour.), an underutilised, aquatic leafy vegetable, based on high resolution accurate mass analysis. The methanolic extract of ...helencha leaves was screened by ultra-high performance liquid chromatography with quadrupole time of flight mass spectrometry (LC-QToF-MS). An in-house developed database of phytochemical metabolites was referred for compound identifications. Based on the detection of the pseudomolecular ion and at least one molecule-specific fragment ion (each with < 5 ppm of mass error), 25 potentially-bioactive phenolic compounds were putatively identified. These included 6 flavonols, 4 phenolic acids, 3 lignans, 3 flavones and 1 each of flavanol, flavanone, dihydroflavonol, tetramethoxyflavone, isoflavonoid and methylated flavonol. In addition, 3 unclassified compounds are also reported. The helencha extract showed antibiofilm properties with a potent bacteriostatic activity against the clinical isolates of
Pseudomonas aeruginosa
, a human pathogenic bacteria. The complementary molecular docking studies indicated strong binding interactions of the identified compounds with the active site of LasR protein of
P. aeruginosa.
The in vitro and in silico study results would be useful to develop novel neutraceutical products based on helencha-extract and design new lead compounds to control the biofilm producing pathogenic microorganisms.
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