CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 9
·e202200118
·
IF 2.745
Bing-Kang Sun,Rui-Yu Wang,Bei Li,Xing Fan,Yuan Zhou,Bing Gu,Yang-Yang Yan
A rapid and accurate analytical method was established to identify CREC and CSEC. Orbitrap-MS was used to detect the polypeptide of CREC and CSEC strains, and MS data were analyzed by pattern recognition analyses such as hierarchical cluster analysis (HCA), principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). HCA based on the farthest distance method could well distinguish the two types of E. coli , and the cophenetic correlation coefficient of the farthest distance method was 0.901. Comparing the results of PCA, PLS-DA, and OPLS-DA, OPLS-DA exhibited the highest accuracy in predicting the CREC and CSEC strains. A total of 26 compounds were identified, and six of the compounds were the highly significant difference between the two types of strains. MS combined with pattern recognition can achieve a more comprehensive and efficient statistical analysis of complex biological samples. Graphical
研究领域:
微生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2022
·Vol. 10
·期 6
·
IF 9.043
Shuyi Wang,Qi Ding,Yawei Zhang,Anru Zhang,Qi Wang,Ruobing Wang,Xiaojuan Wang,Longyang Jin,Shuai Ma,Hui Wang
Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is recognized as a threat worldwide, but the mechanisms underlying its emergence remain unclear. As most CR-hvKP isolates are not hypermucoviscous, we speculated that the evolution of the capsule might result in the convergence of carbapenem resistance and hypervirulence. Here, 2,096 K. pneumoniae isolates were retrospectively collected to screen the ST23-K1 clone, and hypervirulence was roughly defined as being highly resistant to serum killing. The effect of wcaJ on the capsule, virulence, fitness, and resistance acquisition was further analyzed. The capsule gene wcaJ, inserted by ISKpn26/ISKpn74, was identified via whole-genome sequencing in four hvKP, but not hypermucoviscous, isolates. Uronic acid quantitation results revealed that these isolates produced significantly less capsular polysaccharides than NTUH-K2044. A significant increase in capsular production was observed in wcaJ-complemented isolates and confirmed by transmission electron microscopy. Further, all wcaJ-complemented isolates acquired greater resistance to macrophage phagocytosis, and one representative isolate resulted in a significantly higher mortality rate than the parental isolate in mice, indicating that wcaJ inactivation might compromise virulence. However, isolates with wcaJ interruption demonstrated a lower fitness cost and a high conjugation frequency of the blaKPC-2 plasmid, raising concerns about the emergence of carbapenem resistance in hvKP.IMPORTANCE Klebsiella pneumoniae is one of the most common nosocomial pathogens worldwide, and we speculated that the evolution of the capsule might result in the convergence of carbapenem resistance and hypervirulence of K. pneumoniae. The wcaJ gene was first reported to be interrupted by insertion sequence elements in ST23-K1 hypervirulent Klebsiella pneumoniae, resulting in little capsule synthesis, which plays an important role in virulence. We examined the effect of wcaJ on the capsule, virulence, and fitness. Isolates with wcaJ interruption might compromise virulence and demonstrated a lower fitness cost and a high conjugation frequency of the blaKPC-2 plasmid, highlighting its role as a potential factor facilitating hypervirulence and carbapenem resistance.
研究领域:
微生物学
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感染病学
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基因组学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Dumei Ma,Yongqi Wang,Jiacheng Ye,Chao Xin,Chuan-Fan Ding,Yinghua Yan
Carbapenem resistance and hypervirulence represent two distinct evolutionary pathways in Klebsiella pneumoniae, posing significant challenges in clinical settings. Of particular concern are convergent strains that combine both traits, complicating timely diagnosis and treatment. Herein, we present a novel MOF-derived bimetallic nanocube hybrid nanosheet (denoted Pt-G@Cu5Zn8C@Au) designed to enhance laser desorption/ionization mass spectrometry (LDI-MS) in distinguishing convergent strains from other variants. The novel material, synthesized through the pyrolysis of pristine MOFs, features uniformly distributed Cu and Zn synergistic metal sites within the carbon matrix, addressing critical limitations of current nanomatrices for in situ extraction of metabolic fingerprints from microbial cells, such as limited sensitivity (e.g., amorphous silicon, TiO2, and metal nanoparticles) or relatively weak conductivity and stability (MOF-based materials). Utilizing this advanced matrix, the metabolic fingerprints of 248 K. pneumoniae isolates were rapidly extracted, identifying 23 top VIP-score peaks as potential biomarkers for differentiating convergent strains from their variants. Combined with machine learning, the prediction model achieved 100% accuracy in distinguishing convergent strains from carbapenem-sensitive isolates (CS_cKP) or hypervirulent isolates (hvKP) using the SVM model, while achieving 78.26% accuracy in differentiating them from carbapenem-resistant isolates (CR_cKP) with the KNN/NB models. These findings highlight the high accuracy and efficacy of our assay in distinguishing convergent strains from their variants.
研究领域:
微生物学
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医学诊断
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材料科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Wen-Ba Wang,Jia-Yang Wan,Dao-Jun Yu,Hai-Xia Du,Hui-Fen Zhou,Hai-Tong Wan,Jie-Hong Yang
Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKp) infection poses a significant global public health challenge, with the misuse of antibiotics further contributing to the development of resistance and triggering harmful inflammatory responses. Outer membrane vesicles (OMVs) released by CRKp under sub-lethal concentration of MEM pressure (KOMV-MEM) exhibit enhanced virulence and greater efficiency in transferring resistance genes.Methods: We investigated the inhibitory effects of chlorogenic acid (CA) on KOMV-MEM characteristics and its protective role in KOMV-MEM infected mice. Based on LC-MS proteomic analysis of vesicles, we screened for potential targets of KOMV-MEM in promoting macrophage (MØ) pyroptosis pathways and inducing resistance gene transfer. Subsequently, computational predictions and experimental validation were performed to determine how CA regulates these mechanisms.Results: This study confirmed that, under MEM pressure, the exacerbated infection levels in CRKp-inoculated mice are attributable to the high virulence of KOMV-MEM. Computational and experimental results demonstrated that CA inhibits pyroptosis by reducing MØ capture of KOMV-MEM through blocking the interaction between GroEL and LOX-1. Furthermore, CA prevents the spread of resistance genes by disrupting the conjugation and transfer processes between KOMV-MEM and recipient bacteria. Finally, in vitro and in vivo assays showed that CA inhibits KOMV-MEM resistance enzymes, thereby preventing the hydrolysis of MEM in the environment and depriving susceptible bacteria of protection.Discussion: These findings provide the first confirmation that CA can inhibit both the virulence and the transmission of drug resistance in KOMV-MEM. This underscores the potential of CA treatment as a promising antimicrobial strategy against CRKp infection.
研究领域:
微生物学
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药理学
·
感染与免疫
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 20
·12486
·
IF 6.208
Joanna Xuan Hui Goh,Loh Teng-Hern Tan,Jodi Woan-Fei Law,Kooi-Yeong Khaw,Nurul-Syakima Ab Mutalib,Ya-Wen He,Bey-Hing Goh,Kok-Gan Chan,Learn-Han Lee,Vengadesh Letchumanan
The increasing prevalence of resistance in carbapenems is an escalating concern as carbapenems are reserved as last-line antibiotics. Although indiscriminate antibiotic usage is considered the primary cause for resistance development, increasing evidence revealed that inconsequential strains without any direct clinical relevance to carbapenem usage are harboring carbapenemase genes. This phenomenon indirectly implies that environmental microbial populations could be the ‘hidden vectors’ propelling carbapenem resistance. This work aims to explore the carbapenem-resistance profile ofVibriospecies across diverse settings. This review then proceeds to identify the different factors contributing to the dissemination of the resistance traits and defines the transmission pathways of carbapenem resistance. Deciphering the mechanisms for carbapenem resistance acquisition could help design better prevention strategies to curb the progression of antimicrobial resistance development. To better understand this vast reservoir selecting for carbapenem resistance in non-clinical settings,Vibriospecies is also prospected as one of the potential indicator strains for carbapenem resistance in the environment.
研究领域:
微生物学
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传染病学
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抗生素研究
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分子生物学
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DOI
高影响因子
Engineering
·
2022
·
IF 12.834
Yingbo Shen,Fupin Hu,Yongqiang Wang,Dandan Yin,Lu Yang,Yiqiang Chen,Chunyan Xu,Jiyun Li,Junyao Jiang,Xueyang Wang,Yulin Fu,Dongyan Shao,Dejun Liu,Tengfei Ma,Chang Cai,Zhangqi Shen,Shaolin Wang,Juan Li,Rong Zhang,Yuebin Ke,Congming Wu,Jianzhong Shen,Timothy R. Walsh,Yang Wang
Although carbapenem use is prohibited in animals in China, carbapenem-resistant Escherichia coli (CREC), especially New Delhi metallo-β-lactamase (NDM)-producing strains, are widely prevalent in food-producing animals. At present, the impact of livestock-associated CREC strains on human populations at the national level is unknown. Here, we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence. We also ascertain the bla NDM and bla KPC abundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin. Overall, 631/29 799 (2.1%) clinical Escherichia coli ( E. coli ) isolates were identified as CREC. Multivariable analysis revealed that being male, an age below 1, an age between 13 and 18, provinces with greater chicken production, and provinces with higher pig production were associated with higher odds of CREC infection. In general, 73.8% ( n = 45/61) of pig farms and 62.2% ( n = 28/45) of chicken farms had a bla NDM abundance of 1 × 10 −5 to 1 × 10 −3 and 1 × 10 −3 to 1 × 10 −2 , respectively. Among all the Chinese NDM-positive E. coli ( n = 463) available at the National Center for Biotechnology Information (NCBI), the genomic analysis revealed that bla NDM-5 and IncX3 were the predominant carbapenemase gene-plasmid combination, while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels. All the findings suggest frequent CREC transmission between humans and animals, indicating that further discussions on the use of antibiotics in animals and humans are needed, both in China and across the globe.
研究领域:
微生物学
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公共健康
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基因组学
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DOI
高影响因子
Nanomaterials
·
2024
·Vol. 14
·期 24
·2010
·
IF 4.4
Oznur Caliskan-Aydogan,Chloe Zaborney Kline,Evangelyn C Alocilja
Carbapenem-resistant Enterobacterales (CRE) is an emerging global concern. Specifically, carbapenemase-producing (CP) E. coli strains in CRE have recently been found in clinical, environmental, and food samples worldwide, causing many hospitalizations and deaths. Their rapid identification and characterization are paramount in control, management options, and treatment choices. Thus, this study aimed to characterize the cell surface properties of carbapenem-resistant (R) E. coli isolates and their interaction with glycan-coated magnetic nanoparticles (gMNPs) compared with carbapenem-susceptible (S) E coli . This study used two groups of bacteria: The first group included E. coli (R) isolates harboring carbapenemases and had no antibiotic exposure. Their initial gMNP–cell binding capacity, with cell surface characteristics, was assessed. In the second group, one of the E. coli (R) isolates and E. coli (S) had long-term serial antibiotic exposure, which we used to observe their cell surface characteristics and gMNP interactions. Initially, cell surface characteristics (cell morphology and cell surface charge) of the E. coli isolates were evaluated using confocal laser scanning microscope (LSCM) and a Zetasizer, respectively. The interaction of gMNPs with the E. coli isolates was assessed through LSCM and transmission electron microscope (TEM). Further, the gMNP–cell attachment was quantified as a concentration factor (CF) through the standard plating method. The results showed that the CF values of all E. coli (R) were significantly different from those of E. coli (S), which could be due to the differences in cell characteristics. The E. coli (R) isolates displayed heterogeneous cell shapes (rod and round cells) and lower negative zeta potential (cell surface charge) values compared to E. coli (S). Further, this research identified the differences in the cell surface characteristics of E. coli (S) under carbapenem exposure, compared to unexposed E. coli (S) that impact their attachment capacity. The gMNPs captured more E. coli (S) cells compared to carbapenem-exposed E. coli (S) and all E. coli (R) isolates. This study clearly found that differences in cell surface characteristics impact their interaction with magnetic nanoparticles. The gained insights aid in further understanding adhesion mechanisms to develop or improve bacterial isolation techniques and diagnostic and treatment methods for CRE.
研究领域:
微生物学
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医学诊断
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纳米技术
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DOI
PubMed
高影响因子
Microbiology Spectrum
·
2024
·Vol. 12
·期 10
·
IF 3.7
Karl A. Glen,Iain L. Lamont
Pseudomonas aeruginosa is a highly problematic opportunistic pathogen that causes a range of different infections. Infections are commonly treated with β-lactam antibiotics, including cephalosporins, monobactams, penicillins, and carbapenems, with carbapenems regarded as antibiotics of last resort. Isolates of P. aeruginosa can contain horizontally acquired bla genes encoding β-lactamase enzymes, but the extent to which these contribute to β-lactam resistance in this species has not been systematically quantified. The overall aim of this research was to address this knowledge gap by quantifying the frequency of β-lactamase-encoding genes in P. aeruginosa and by determining the effects of β-lactamases on susceptibility of P. aeruginosa to β-lactams. Genome analysis showed that β-lactamase-encoding genes are present in 3% of P. aeruginosa but are enriched in carbapenem-resistant isolates (35%). To determine the substrate antibiotics, 10 β-lactamases were expressed from an integrative plasmid in the chromosome of P. aeruginosa reference strain PAO1. The β-lactamases reduced susceptibility to a variety of clinically used antibiotics, including carbapenems (meropenem, imipenem), penicillins (ticarcillin, piperacillin), cephalosporins (ceftazidime, cefepime), and a monobactam (aztreonam). Different enzymes acted on different β-lactams. β-lactamases encoded by the genomes of P. aeruginosa clinical isolates had similar effects to the enzymes expressed in strain PAO1. Genome engineering was used to delete β-lactamase-encoding genes from three carbapenem-resistant clinical isolates and increased susceptibility to substrate β-lactams. Our findings demonstrate that acquired β-lactamases play an important role in β-lactam resistance in P. aeruginosa, identifying substrate antibiotics for a range of enzymes and quantifying their contributions to resistance.
研究领域:
微生物学
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医学
·
基因组学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Suo Decheng,Fan Xia,Xiao Zhiming,Liyang,Wang Peilong
A simple and accurate method of ultra high performance liquid chromatography (UHPLC) coupled with quadrupole-high field Orbitrap high-resolution mass spectrometry (QE HF HRMS) has been developed for analyzing 8 trace-level (µg/L) carbapenems in milk. Mass spectrometry conditions, chromatographic conditions, extraction solvent and QuEChERS procedures were optimized for determination of 8 carbapenems in milk. Samples were extracted and purified by modified QuEChERS procedure. Good separation for 8 carbapenems s was achieved with a PFP column at 8 min. Method validation results showed the linear ranges are 1–100 µg/L to 10–1,000 µg/L, the correlation coefficients are more than 0.995, and the recoveries of spiked samples are 79.3%–104% with a relative standard deviation less than 15%. This method successfully applied to monitor residue of carbapenems in real milk, four kinds of carbapenems have been detected in 8 sample of 79 collected milks with concentration ranged between 15 µg/L∼3,325 µg/L.
研究领域:
分析化学
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食品安全
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
·
2017
·Vol. 37
·期 1
·141-148
·
IF 2.727
Ng S. M. S.,Sioson J. S. P.,Yap J. M.,Ng F. M.,Ching H. S. V.,Teo J. W. P.,Jureen R.,Hill J.,Chia C. S. B.
The global emergence of carbapenem-resistant Enterobacteriaceae (CRE) presents a significant clinical concern, prompting the WHO to prioritize CRE as a top priority pathogen in their 2017 global antibiotic-resistant bacteria priority list. Due to the fast-depleting antibiotic arsenal, clinicians are now resorting to using once-abandoned, highly toxic antibiotics such as the polymyxins and aminoglycosides, creating an urgent need for new antibiotics. Drug repurposing, the application of an approved drug for a new therapeutic indication, is deemed a plausible solution to this problem. A total of 1,163 FDA-approved drugs were screened for activity against a clinical carbapenem- and multidrug-resistant E. coli isolate using a single-point 10 μM assay. Hit compounds were then assessed for their suitability for repurposing. The lead candidate was then tested against a panel of clinical CREs, a bactericidal/static determination assay, a time-kill assay and a checkerboard assay to evaluate its suitability for use in combination with Tigecycline against CRE infections. Three drugs were identified. The lead candidate was determined to be Zidovudine (azidothymidine/AZT), an oral anti-viral drug used for HIV treatment. Zidovudine was shown to be the most promising candidate for use in combination with Tigecycline to treat systemic CRE infections. Further experiments should involve the use of animal infection models.
研究领域:
微生物学
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感染病学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 12
·期 1
·104-111
·
IF 2.378
Jianmin Wang,Wei Yang,Qiling Peng,Daobin Han,Liangsheng Kong,Lu Fan,Min Zhao,Shijia Ding
Rapid and simple detection of carbapenem-resistant Enterobacteriaceae (CRE) is important to manage infection and prevent the spread of these bacteria. In this work, we utilize pH response to detect CRE in urine rapidly. By using vancomycin-modified Fe3O4@Au nanoparticles (Fe3O4@Au@VanNPs), CRE in urine were enriched and separated efficiently via vancomycin–cell wall interaction. More importantly, carbapenemases released via CRE lysis were detected using a pH metre which responded to hydrogen ions generated from imipenem hydrolysis. Thus, the concentration of CRE in urine was detected via the carbapenemase hydrolysis reaction. The proposed method demonstrated a good linear relationship in the range of 104–108 cfu mL−1 for CRE with the limit of detection estimated to be 1.0 × 103 cfu mL−1. More importantly, this method successfully detected clinically isolated CRE strains in urine samples within 3.5 h. Thus, this biosensing strategy might have the potential for practical application in the rapid detection of various resistant bacteria.
研究领域:
微生物学
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医学检验
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Microbiology
·
2023
·
IF 5.2
Wei Liu,Guang Chen,Keke Dou,Bingcheng Yi,Danyang Wang,Qihui Zhou,Yunbo Sun
Multidrug-resistant (MDR) bacterial infections have gained increasing attention due to the high incidence rates and high mortality, especially for the carbapenem-resistant Klebsiella pneumoniae (CRKP) infection that can cause severe complications (e.g., pneumonia and sepsis) in multiple organs. Therefore, the development of new antibacterial agents against CRKP is imperative. Inspired by natural plant antibacterial agents with broad-spectrum antibacterial properties, the antibacterial/biofilm activity of eugenol (EG) on CRKP and their underlying mechanisms are investigated in our work. It is found that EG exhibits remarkable inhibitory effects on planktonic CRKP in a dose-dependent fashion. Meanwhile, the destruction of membrane integrity induced by the formation of reactive oxygen species (ROS) and glutathione reduction results in the leakage of bacterial cytoplasmic components, including DNA, β-galactosidase, and protein. Moreover, when EG contacts with bacterial biofilm, the whole thickness of the dense biofilm matrix decreases, and the integrity is destroyed. Overall, this work verified that EG could eliminate CRKP via ROS-induced membrane rupture, which offers vital evidence to explain the antibacterial ability of EG against CRKP.
研究领域:
微生物学
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药理学
·
传染病学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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