Ruichao Li - Academia.edu (original) (raw)

Papers by Ruichao Li

ESBLs‐producing Escherichia coli from sheep‐origin: Genome‐wide virulence genes identification and in vivo virulence assessment in mice and Galleria mellonella

Transboundary and Emerging Diseases

Antimicrobial Agents and Chemotherapy

Here, we characterized a carbapenem-resistant Vibrio diabolicus strain of shrimp origin with vari... more Here, we characterized a carbapenem-resistant Vibrio diabolicus strain of shrimp origin with various experiments and bioinformatics analysis. A novel metallo-β-lactamase (MBL) gene, bla VMB-2 , that confers resistance to β-lactams, including meropenem and cephalosporins, was identified on a plasmid-borne composite transposon, IS Shfr9 -IS CR1 - bla VMB-2 - bla CARB-12 - aadA1- IS Shfr9 , which is capable of generating a bla VMB-2 -bearing circular intermediate. IS Shfr9 was found to be disseminated in multidrug-resistant (MDR) pathogens, arousing the concern of further transmission of a bla VMB-2 -bearing circular intermediate to clinical Enterobacterales strains via such insertion sequences, which warrants further investigations.

Frontiers in Microbiology, Apr 6, 2022

Sodium dehydroacetate confers broad antibiotic tolerance by remodeling bacterial metabolism

Journal of Hazardous Materials, 2022

Antibiotic tolerance has been a growing crisis that is seriously threatening global public health... more Antibiotic tolerance has been a growing crisis that is seriously threatening global public health. However, little is known about the exogenous factors capable of triggering the development of antibiotic tolerance, particularly in vivo. Here we uncovered that an previously approved food additive termed sodium dehydroacetate (DHA-S) supplementation remarkably impaired the activity of bactericidal antibiotics against various bacterial pathogens. Mechanistic studies indicated that DHA-S induced glyoxylate shunt and reduced bacterial cellular respiration by inhibiting the enzymatic activity of α-ketoglutarate dehydrogenase (α-KGDH). Furthermore, DHA-S mitigated oxidative stress imposed by bactericidal antibiotics and enhanced the function of multidrug efflux pumps. These actions worked together to induce bacterial tolerance to antibiotic killing. Interestingly, the addition of five exogenous amino acids, particularly cysteine and proline, effectively reversed antibiotic tolerance elicited by DHA-S both in vitro and in mouse models of infection. Taken together, these findings advance our understanding of the potential risks of DHA-S in the treatment of bacterial infections, and shed new insights into the relationships between antibiotic tolerance and bacterial metabolism.

Diversity and Genomic Characterization of mcr-1 Positive Conjugative Plasmids in Foodborne Escherichia coli and Clinical Salmonella

The 7 mcr-1-bearing plasmid sequences and 3 recipients plasmid sequences were ... more The 7 mcr-1-bearing plasmid sequences and 3 recipients plasmid sequences were deposited here for reference. The Nanopore long reads were shared for understanding the tandem repeats of mcr-1.

Nine plasmids carrying mcr-1 and tet(X4)

Two plasmids pCLDRW_444k and pCLDRF_341k carrying mcr-1 and tet</i... more Two plasmids pCLDRW_444k and pCLDRF_341k carrying mcr-1 and tet(X4) were constructed through conjugation assays, and seven evolved plasmids carrying mcr-1 and tet(X4) from pCLDRW_444k were acquired after long evolutionary processes

Emergence of a plasmid in Klebsiella pneumoniae ST15

The raw nanopore long-read data generated for strains KP17-15 and KP17-16 with the RBK004 kit.

Wearable and antibacterial HPMC-anchored conductive polymer composite strain sensor with high gauge factors under small strains

Chemical Engineering Journal, 2022

Loureirin B alleviates cardiac fibrosis by suppressing Pin1/TGF-β1 signaling

European Journal of Pharmacology, 2022

It is well-established that cardiac fibrosis contributes to cardiac dysfunction and adverse outco... more It is well-established that cardiac fibrosis contributes to cardiac dysfunction and adverse outcomes. However, the underlying mechanisms remain elusive, warranting further studies to develop new therapeutic strategies. It has been suggested that loureirin B can ameliorate the progression of fibrotic diseases. This study investigated the effects of loureirin B on cardiac fibrosis and explored the underlying mechanisms. Transverse aortic constriction (TAC) was performed to induce cardiac fibrosis in mice. Loureirin B (10 mg/kg/day) or saline was continuously delivered via subcutaneous osmotic mini-pumps. Cardiac fibroblasts (CFs) were treated with angiotensin II (Ang II, 100 nM, 24 h) to simulate fibrosis in vitro. Immunochemistry, echocardiography, and Sircol collagen assays were conducted to evaluate the cardioprotective effects. Quantitative real-time polymerase chain reaction, Western blot, and transfection techniques were performed to elucidate the mechanisms. Results showed that loureirin B prevented cardiac fibrosis and improved cardiac function in mice subjected to TAC. Treatment with loureirin B inhibited the elevation of inflammatory factors (interleukin-1β, interleukin-6, and tumor necrosis factor-α), transforming growth factor-β1 (TGF-β1), and Pin1 induced by TAC. Furthermore, loureirin B treatment inhibited the increased fibroblast activation and collagen synthesis induced by Ang II in CFs. In addition, loureirin B inhibited increased expression of TGF-β1 and Pin1 induced by Ang II or TAC. Mechanistically, overexpression of Pin1 induced increased TGF-β1 expression and blocked the anti-fibrotic effects in Ang II-induced CFs treated with loureirin B. Loureirin B ameliorated cardiac fibrosis and dysfunction both in vitro and in vivo probably through the Pin1/TGF-β1 signaling pathway.

Raw reads for 12 MinION sequencing samples and 21 assembled plasmids

These twelve samples were MDR plasmids sequenced in a single MinION nanopore sequencing run with ... more These twelve samples were MDR plasmids sequenced in a single MinION nanopore sequencing run with SQK-RBK001 kit.

Demise of mcr-1 and mcr-3.19 mediated by plasmid elimination and ISApl1

The sequences in the three files were assembled sequenes of plasmids found in three danghter clon... more The sequences in the three files were assembled sequenes of plasmids found in three danghter clones with flye tool based on Nanopore MinION long-read data.

Sequences of tet(X)-bearing plasmidome and ICE

The 27 tet(X4)-bearing plasmid sequences and 1 tet(X6)-bearing ICE sequence were deposited here f... more The 27 tet(X4)-bearing plasmid sequences and 1 tet(X6)-bearing ICE sequence were deposited here for reference. The Nanopore long reads were shared for understanding the tandem repeats of tet(X4). Also, 26 whole genome sequences assembled by Illumina short-read data were shared here.

Paclitaxel and its derivative facilitate the transmission of plasmid-mediated antibiotic resistance genes through conjugative transfer

Science of The Total Environment, 2022

The rapid dissemination of antibiotic resistance by horizontal gene transfer (HGT) renders the gl... more The rapid dissemination of antibiotic resistance by horizontal gene transfer (HGT) renders the global resistance crisis more tense and urgent as few effective antimicrobials are available to combat multidrug-resistant (MDR) pathogens at present. Conjugation is one of the most dominant and representative pathways of HGT. Antibiotic residue in environment is recognized as an important accelerator for conjugal transfer, whereas the roles of non-antibiotic pharmaceuticals in this process are not fully understood. Here we found that environmentally relevant concentrations of paclitaxel as well as its derivative docetaxel, two commonly used anticancer drugs, remarkably facilitated the conjugative transfer of resistance plasmids carrying multiple antibiotic resistance genes (ARGs). The underlying mechanisms of the enhanced conjugation were investigated by detecting the activity of RpoS regulon, membrane permeability, SOS response and gene expression of conjugative transfer systems. Our results showed that paclitaxel induced a series of cellular responses, including up-regulation of rpoS expression, activated SOS response, increased cell membrane permeability, enhanced plasmid replication and mating pilus formation. Collectively, our data provide new insight on the roles of paclitaxel and its derivative in promoting the conjugal transfer of ARGs, highlighting the importance of good antimicrobial stewardship.

Food Control, 2021

To investigate the characteristics of tet(X4)-carrying E. coli from retail raw meat, three hundre... more To investigate the characteristics of tet(X4)-carrying E. coli from retail raw meat, three hundred and eleven retail raw meat samples including chicken, pork, duck, and beef were collected for screening for tigecycline resistant isolates in Sichuan Province, China. We detected 25 (8.0%, 95%CI: 5.3%-11.6%) tet(X4) positive E. coli isolates from 311 retail meat with the highest prevalence (13.4%, 95%CI: 7.3%-21.8%) observed in pork. All the tet(X)carrying isolates were analyzed by antimicrobial susceptibility testing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), conjugation experiments, and whole genome sequencing (WGS) to study the phylogenetic relationship and genomic characteristics. Conjugation and S1-PFGE profiling showed 6 isolates (24.0%) successfully transferred the resistant phenotype with frequencies from 3.63 × 10 − 5 to 7.68 × 10 − 2. Simultaneously, tet(X4), floR, and the characteristic structure of adjacent abh gene and cassette flanked by ISCR2 were identified in all 25 isolates, and a structure of abh-tet(X4)-ISCR2-virD2-floR was aligned as an important genetic pattern around tet(X4). Two dominant sequence types (STs) ST1638 (n = 4) and ST48 (n = 4) were identified by in silico MLST. Single nucleotide polymorphisms analysis revealed two potential clone-like transmission clusters which showed high concordance with the local spatio-temporal epidemiology, suggesting that clonal transmission events were very likely. The presence of tet(X4) in multiple different clone complexes (CCs) and the identification of two clone-like transmission indicates its potentially extensive and successful spread among different foodproducing animals.

Microbiology Spectrum, 2021

Tigecycline was considered the last-line drug against serious infections caused by multidrug-resi... more Tigecycline was considered the last-line drug against serious infections caused by multidrug-resistant Gram-negative bacteria. However, the plasmid-mediated tigecycline resistance gene tet (X) has been widely reported in different sources of Enterobacterales and Acinetobacter in China.

Molecular characterization of two novel NDM-1-producing atypical enteroaggregative Escherichia coli isolates from patients

Plasmid, 2021

To investigate NDM-1-producing atypical Enteroaggregative Escherichia coli (aEAEC) of sequence ty... more To investigate NDM-1-producing atypical Enteroaggregative Escherichia coli (aEAEC) of sequence type (ST) 349 from hospitalized patients, the isolates 13ZX28 and 13ZX36 were subjected to antimicrobial susceptibility testing, conjugation and whole genome sequencing. Only two single nucleotide mutations were detected in chromosomes despite different plasmid profiles. Both isolates were positive for blaNDM-1 mediating resistance to carbapenem. A novel plasmid p13ZX28-272 (~272-kb) from 13ZX28 encodes blaNDM-1. Interestingly, its sequence was identical to the two plasmids p13ZX36-200 (~200-kb) and p13ZX36-70 (~70-kb) from 13ZX36. Formation of the former episome possibly involved homologous recombination through a 4948-bp large fragment located on each of the two latter plasmids. Furthermore, plasmid p13ZX28-272 could be resolved into a ~ 98-kb daughter plasmid by IS26 rearrangement following conjugation. The plasticity of the plasmids is recognized, which warrants further investigation to evaluate the underlying public health risk and understand how antibiotic selection pressure drives this process.

PK/PD integration and pharmacodynamic cutoff of cefquinome against cow mastitis due to Escherichia coli

Journal of Veterinary Pharmacology and Therapeutics, 2021

Cefquinome is the fourth generation of cephalosporin approved solely in animal usage. In order to... more Cefquinome is the fourth generation of cephalosporin approved solely in animal usage. In order to slow down the resistance development of E. coli to cefquinome, and to protect and maintain the effectiveness of cefquinome, an ex vivo PK/PD modeling of cefquinome against E. coli in cows after intramammary infusion administration was conducted. The epidemiologic cutoff (ECOFF) and pharmacodynamic cutoff (COPD) of cefquinome against E. coli in lactation cows after intramammary infusion administration were recommended. The MICs of cefquinome against 1073 clinical E. coli isolates ranged from 0.015 to >64 μg/ml, and the ECOFF was defined as 0.125 μg/ml. The pharmacokinetic results showed that cefquinome maintained high concentration in milk for a long period with the T1/2β of 10.60 h after intramammary infusion in dairy cows. The drug concentration in skimmed milk was still as high as 0.15 mg/ml after 48 h. Cefquinome displayed bacterial killing effect at 2× MIC with the initial inoculum of 106 cfu/ml in vitro; however, the same effect was attained with a concentration as high as 32× MIC with the initial inoculum of 108 cfu/ml both in artificial medium and in skimmed milk. The initial inoculum is an important factor on time-killing curve accounting for weakened killing pattern of cefquinome. The AUC0-24 h /MIC index correlated well with ex vivo efficacy. The AUC0-24 h /MIC values for bactericidal effect were 50, 016, and 67,644, respectively, for initial inoculum of 106 and 108 cfu/ml, indicating the bacterial loading or the severity of infection would infect the PK/PD modeling results. The ex vivo PK/PD-based population dose prediction indicated a target attainment rate (TAR) at the existing daily dose (75 mg/udder) of 84.77% against E. coli. Thus, it was recommended as rational dosage. The COPD of cefquinome against E. coli was determined as 8 μg/ml at the dose of 75 mg/udder. The derived ECOFF, COPD, together with ex vivo PK/PD-based population dose prediction served as important steps in the establishment of optimum dose regimen and provided a useful interpretative criterion to categorize the antimicrobial susceptibility testing results of cefquinome.

Simulated response of the active layer thickness of permafrost to climate change

Atmospheric and Oceanic Science Letters, 2021

The active layer thickness (ALT) in permafrost regions, which affects water and energy exchange, ... more The active layer thickness (ALT) in permafrost regions, which affects water and energy exchange, is a key variable for assessing hydrological processes, cold-region engineering, and climate change. In this study, the authors analyzed the variation trends and relative changes of simulated ALTs using the Chinese Academy of Sciences Land Surface Model (CAS-LSM) and the Chinese Academy of Sciences Flexible Global Ocean–Atmosphere–Land System Model, gridpoint version 3 (CAS-FGOALS-g3). Firstly, the simulated ALTs produced by CAS-LSM were shown to be reasonable by comparing them with Circumpolar Active Layer Monitoring observations. Then, the authors simulated the ALTs from 1979 to 2014, and their relative changes across the entire Northern Hemisphere from 2015 to 2100. It is shown that the ALTs have an increasing trend. From 1979 to 2014, the average ALTs and their variation trends over all permafrost regions were 1.08 m and 0.33 cm yr−1, respectively. The relative changes of the ALTs ra...

Frontiers in Microbiology, 2021

The emergence of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) was regarded ... more The emergence of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) was regarded as an emerging threat in clinical settings. Here, we investigated the prevalence of CRKP strains among inpatients in a new hospital over 1 year since its inception with various techniques, and carried out a WGS-based phylogenetic study to dissect the genomic background of these isolates. The genomes of three representative blaNDM–1-positive strains and the plasmids of four blaKPC–2-positive strains were selected for Nanopore long-read sequencing to resolve the complicated MDR structures. Thirty-five CRKP strains were identified from 193 K. pneumoniae isolates, among which 30 strains (85.7%) harbored blaKPC–2, whereas the remaining five strains (14.3%) were positive for blaNDM–1. The antimicrobial resistance profiles of blaNDM–1-positive isolates were narrower than that of blaKPC–2-positive isolates. Five isolates including two blaNDM–1-positive isolates and three blaKPC–2-positive strain...

Simulated Spatial and Temporal Distribution of Freezing and Thawing Fronts in CAS‐FGOALS‐g3

Journal of Advances in Modeling Earth Systems, 2021

In this study, we implement a new frozen‐soil parameterization scheme into the climate system mod... more In this study, we implement a new frozen‐soil parameterization scheme into the climate system model CAS‐FGOALS‐g3 to investigate the dynamic changes of freezing and thawing fronts and the effects arising from thermal processes and climate. Simulations are conducted using the developed model to validate its performance relative to multi‐source observations. It is shown that the model could reasonably reproduce soil freezing and thawing processes, including dynamic changes in freezing and thawing fronts. The historical simulation shows that the maximum freeze depth increases with an increase of latitude in seasonally frozen ground, and the active layer thickness decreases with an increase of latitude in permafrost regions. The active layer thickness shows increasing trends while the maximum freeze depth shows decreasing trends, which is consistent with change in the 2‐m air temperature. In conclusion, these results have the potential to further deepen our understanding of the freeze‐thaw cycle process and the historical response of permafrost to climate change.