The continuous emergence of carbapenem-resistant
Escherichia coli
(CRECO) presents a great challenge to public health. New Delhi metallo-lactamase (NDM) variants are widely disseminated in China, so ...the research on the prevalence and transmission of diverse
bla
NDM
variants is urgently needed. In the present study, 54 CRECO isolates were collected from 1,185
Escherichia coli
isolates in five hospitals in Northern Jiangsu Province, China from September 2015 to August 2016. Antimicrobial susceptibility tests, PCR detection of resistance determinants, multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to characterize these strains. Plasmid conjugation experiments were carried out to determine the transferability of resistant genes from selected isolates. PCR-based replicon typing (PBRT), S1 nuclease-PFGE, and Southern blotting were conducted for plasmid profiling. Carbapenemase genes were detectable in all CRECO isolates, among which thirty-one CRECO isolates were found to carry
bla
NDM−5
(54.7%), while,
bla
NDM−1
,
bla
NDM−7
,
bla
NDM−4
,
bla
NDM−9
, and
bla
KPC−2
were identified in 14, five, two, one, and one isolates, respectively. MLST results revealed 15 different STs and four new STs were first reported to be linked with NDM-producing isolates. PFGE typing showed that no more than two isolates with the same ST appeared to the same band pattern except three ST410 isolates. Twenty-six selected NDM-producing isolates were successfully transferred to
E. coli
J53 by conjugation experiments. Notably, 50.0% (13/26) of
bl
a
NDM
variants were found to be carried by ~55 kb IncX3 plasmid. Our study reported a high prevalence of
bl
a
NDM
variants, especially
bla
NDM−5
, in Northern Jiangsu province, China. Diverse
bla
NDM
variants were mainly carried by ~55 kb IncX3 plasmids, suggesting that the fast evolution and high transferability of this kind of plasmid promote the high prevalence of
bla
NDM
variants. Therefore, large-scale surveillance and effective infection control measures are also urgently needed to prevent diverse
bla
NDM
variants from becoming epidemic in the future.
Liposomes are the most widely used nanocarrier platform for the delivery of therapeutic and diagnostic agents, and a number of liposomes have been approved for use in clinical practice. After ...systemic administration, most liposomes are cleared by macrophages in the mononuclear phagocyte system, such as the liver and bone marrow (BM). However, the majority of studies have focused on investigating the therapeutic results of liposomal drugs, and too few studies have evaluated the potential side effects of empty nanocarriers on the functions of macrophages in the mononuclear phagocyte system. Here, we evaluate the potential effects of empty liposomes on the functions of BM niche macrophages. Following liposome administration, we observed lipid droplet (LD) accumulation in cultured primary macrophages and BM niche macrophages. We found that these LD-accumulating macrophages, similar to foam cells, exhibited increased expression of inflammatory cytokines, such as IL-1β and IL-6. We further provided evidence that liposome deposition and degradation induced LD biogenesis on the endoplasmic reticulum membrane and subsequently disturbed endoplasmic reticulum homeostasis and activated the inositol-requiring transmembrane kinase/endoribonuclease 1α/NF-κB signaling pathway, which is responsible for the inflammatory activation of macrophages after liposome engulfment. Finally, we also showed the side effects of dysfunctional BM niche macrophages on hematopoiesis in mice, such as the promotion of myeloid-biased output and impairment of erythropoiesis. This study not only draws attention to the safety of liposomal drugs in clinical practice but also provides new directions for the design of lipid-based drug carriers in preclinical studies.
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In this study, a surface-enhanced resonance Raman scattering (SERRS) method has been developed for the accurate detection and identification of carbapenem-resistant and carbapenem-sensitive
. A total ...of 89 human isolates of Enterobacteriaceae, comprising 41 strains of carbapenem-sensitive
(CSEC) and 48 strains of carbapenem-resistant
(CREC), were tested to assess the feasibility of our proposed SERRS method as a clinical tool, and the results showed almost 100% accuracy.
•Three unduplicated non-O1/non-O139 Vibrio cholerae strains were isolated from hepatitis B cirrhosis patients.•Neither antibiotics resistance nor virulence genes were detected.•The novel allele (gyrB ...97) and two novel sequence types (ST518, ST519) were identified.
We aimed to report virulence-associated genes and molecular characteristics of non-O1/non-O139 Vibrio cholerae isolated from hepatitis B cirrhosis patients in China.
Patient clinical data including course of disease, laboratory tests, antibiotic treatment and outcomes were collected. Antimicrobial susceptibility testing was performed and virulence-associated genes were detected by PCR. Genetic relatedness among non-O1/non-O139 V. cholerae strains was investigated by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).
All three strains in this study harbored pathogenicity related genes like rtxA, rtxC, toxR, hapA, hlyA and ompW whereas they lacked ctxA, ctxB, tcpA, ompU and zot genes. None of them showed resistance to any antibiotic detected. A new allele of gyrB was submitted to the MLST database and designated as 97. Two novel sequence types (ST518 and ST519) and ST271 were identified by multilocus sequence typing (MLST). PFGE indicated considerable diversity among three non-O1/non-O139 V. cholerae strains.
Three sporadic cases highlight that non-O1/non-O139 V. cholerae can cause opportunistic invasiveness infection in cirrhosis patients. Pathogenicity may be related to virulence-associated genes. Timely detection and antibiotic therapy should be paid more attention to in clinic.
In clinical practice, infections caused by Aspergillus species are common and associated with high mortality rates. However, isolating Aspergillus from clinical samples and cultures is challenging, ...and serological tests cannot differentiate between strains. Furthermore, the complex cell wall structure in Aspergillus species hinders DNA extraction and subsequent nucleic acid detection. Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger are common and frequently encountered pathogenic species. This study aimed to establish an efficient and rapid method for detecting Aspergillus species in clinical samples. Fe3O4@PEI.NH2 nanoparticles with large particle sizes were employed to capture Aspergillus from the samples. Flexible silver nanowires (AgNWs) were prepared and used as the surface-enhanced Raman scattering (SERS) substrate for Aspergillus detection. Through SERS spectroscopy, the identification of captured Aspergillus species was confirmed. Furthermore, the SERS spectrum underwent principal component analysis employing orthogonal partial least-squares discrimination analysis (OPLS-DA) as a multivariate analysis technique to distinguish between the various Aspergillus species effectively. After 10-fold cross-validation, the trained model achieved a testing accuracy of 99.15%, indicating excellent classification performance. By utilizing pre-prepared Fe3O4@PEI.NH2 and AgNWs, the detection process was completed within 60 min without disrupting the cell wall of Aspergillus.
•A rapid SERS detection method for Aspergillus was reported.•Particle size Fe3O4@PEI.NH2 was proposed for capture and high capture performance for Aspergillus.•AgNWs as enhanced substrate can better bind to Aspergillus.•The detection time was only 60 min.
•The values of laboratory indicators in 35 articles were integrated.•The laboratory indexes of severe and non-severe patients infected with COVID-19 has been compared.•Indicators that may most ...effectively predict a non-severe COVID-19 patient develop into a severe patient have been concluded.
The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient.
We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles.
Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin (1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1β (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold).
Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.
Rapid dissemination of antibiotic resistance genes among bacterial isolates is an increasing problem in China. Integron, a conserved DNA sequence, which is carried on episomal genetic structures, ...plays a very important role in development of antibiotic resistance. This systematic analysis was based on MEDLINE and EMBASE databases. We summarized the distribution and proportion of different types of gene cassette arrays of integrons (including class 1, 2, 3 and atypical class 1 integron) from clinical bacteria isolates in China. Fifty-six literatures were included in this study. Most of the strains were Gram-negative bacteria (94.1%, 7,364/7,822) while only 5.9% strains were Gram-positive bacteria. Class 1 integrons were detected in 54.2% (3956/7295) Gram-negative strains. aadA2 was the most popular gene cassette array detected from 60 Gram-positive bacteria while dfrA17-aadA5 were detected in 426 Gram-negative bacteria. This study identified 12 novel gene cassette arrays which have not been previously found in any species. All the novel gene cassette arrays were detected from Gram-negative bacteria. A regional characteristic of distribution of integrons was presented in this study. The results highlight a need for continuous surveillance of integrons and provide a guide for future research on integron-mediated bacteria resistance.
Abstract
Objectives
Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been increasingly reported in China. Here, a multicentre, longitudinal surveillance study on CR-hvKP is ...described.
Methods
We retrospectively investigated carbapenem-resistant K. pneumoniae (CRKP) in 56 centres across China during 2015–17 and screened the virulence genes (iucA, iroN, rmpA and rmpA2) for the presence of virulence plasmids. Hypermucoviscosity, serum killing and Galleria mellonella lethality experiments were conducted to identify CR-hvKP among strains with all four virulence genes. Capsule typing, fitness and plasmid features of CR-hvKP were also investigated.
Results
A total of 1052 CRKP were collected. Among these, 34.2% (360/1052) carried virulence genes and 72 of them had all four of the virulence genes tested. Fifty-five (76.4%) were considered to be CR-hvKP using the G. mellonella infection model, with KPC-2-producing K64-ST11 being the most common type (80%, 44/55). Prevalence of CR-hvKP differed greatly between regions, with the highest in Henan (25.4%, 17/67) and Shandong (25.8%, 25/97). A significant increase in CR-hvKP among KPC-2-producing ST11 strains was observed, from 2.1% (3/141) in 2015 to 7.0% (23/329) in 2017 (P=0.045). Alarmingly, compared with classic CRKP, no difference in growth was found among CR-hvKP (P=0.7028), suggesting a potential risk for dissemination. The hybrid virulence and resistance-encoding plasmid evolved from pLVPK and the resistance plasmid harbouring blaKPC-2, indicating evolution existed between the hypervirulence and hyper-resistance plasmid.
Conclusions
CR-hvKP were more frequently detected than previously assumed, especially among KPC-2-producing ST11. Dissemination of hypervirulence could be extremely rapid due to limited fitness cost. Also, the evolution of resistance genes into hypervirulence plasmids was identified, presenting significant challenges for public health and infection control.
Background: An ESBL, carbapenemase- and MCR-1-producing Escherichia coli ST648 strain was isolated from the urine sample of a patient in a Chinese tertiary hospital in 2016. Methods: The strain was ...fully sequenced by GridION X5 platform of Oxford Nanopore Technology. Results: The sequence analysis showed that the extended-spectrum beta-lactamases CTX-M-65 and OXA-1, the carbapenemase NDM-5, the MCR-1 were encoded, respectively, by three different resistance plasmids. The pE648CTX-M-65-carrying b/a.sub.CTX-M-65 was a novel conjugative plasmid belonging to IncHI2 type; except for the b/a.sub.CTX-M-65, it also carried resistance genes ble, floR, sull, aph(4)-Ia, aac(3)-VI, aac(6')-II, bla.sub.OXA-1, catB, arr3 and tetA. Besides, an IncX4 plasmid pE648MCR-1-carrying mcr-1 and an IncX3 plasmid pE648NDM-5-carrying bla.sub.NDM-5 were also identified. Conclusion: The three transferable resistance plasmids coexisting in the E. coli ST648 isolate indicated the high risk to disseminate the extensively-drug-resistance among Enterobacteriaceae. Keywords: CTX-M-65, MCR-1, NDM-5, extensively-drug-resistance, Escherichia coli
An ESBL, carbapenemase- and MCR-1-producing
ST648 strain was isolated from the urine sample of a patient in a Chinese tertiary hospital in 2016.
The strain was fully sequenced by GridION X5 platform ...of Oxford Nanopore Technology.
The sequence analysis showed that the extended-spectrum β-lactamases CTX-M-65 and OXA-1, the carbapenemase NDM-5, the MCR-1 were encoded, respectively, by three different resistance plasmids. The pE648CTX-M-65-carrying
was a novel conjugative plasmid belonging to IncHI2 type; except for the
, it also carried resistance genes
,
and
. Besides, an IncX4 plasmid pE648MCR-1-carrying
and an IncX3 plasmid pE648NDM-5-carrying
were also identified.
The three transferable resistance plasmids coexisting in the
ST648 isolate indicated the high risk to disseminate the extensively-drug-resistance among Enterobacteriaceae.
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![A Novel [bla.sub.CTX-M-65]-...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1178-6973/small "A Novel [bla.sub.CTX-M-65]-Harboring IncHI2 Plasmid pE648CTX-M-65 Isolated from a Clinical Extensively-Drug-Resistant Escherichia coli ST648")