scholarly journals Qiguiyin Decoction Improves Multidrug-Resistant Pseudomonas aeruginosa Infection in Rats by Regulating Inflammatory Cytokines and the TLR4/MyD88/NF-κB Signaling Pathway

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Guochao Chen ◽  
Wanqiao Zhang ◽  
Lingbo Kong ◽  
Chengxiang Wang ◽  
Xiaojing Lai ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Bacterial Infections ◽  
Early Stage ◽  
Expression Profiles ◽  
Multidrug Resistant ◽  
Antibody Array ◽  
High Morbidity ◽  
High Detection Rate

Pseudomonas aeruginosa (PA), a Gram-negative bacterium, has a high detection rate in hospital-acquired infections. Recently, the frequent appearance of multidrug-resistant (MDR) PA strain with high morbidity and mortality rates has aggravated the difficulty in treating infectious diseases. Due to its multiple resistance mechanisms, the commonly used antibiotics have gradually become less effective. Qiguiyin decoction (QGYD) is a clinically experienced prescription of Chinese herbal medicine, and its combined application with antibiotics has been confirmed to be effective in the clinical treatment of MDR PA infection, which could be a promising strategy for the treatment of drug-resistant bacterial infections. However, the mechanism of QGYD restoring antibiotics susceptibility to MDR PA remains unclear. In the present study, we investigated the effects of QGYD and levofloxacin (LEV) singly or in combination on MDR PA-induced pneumonia rat models. Further analysis was carried out in the serum differential expression profiles of inflammatory cytokines by cytokine antibody array. Besides, the lung TLR4/MyD88/NF-κB signaling pathway was detected by RT-qPCR. Our results showed that based on the treatment of MDR PA-infected rat model with LEV, the combination of QGYD improved the general state and immune organ index. Furthermore, it moderately increased the expressions of proinflammatory cytokines including IL-1β, IL-6, and TNF-α in the early stage of infection and decreased their release rapidly in the later stage, while regulated the same phase change of anti-inflammatory cytokine IL-10. In addition, the adhesion molecule ICAM-1 was significantly downregulated after QGYD combined with LEV treatment. Moreover, the mRNA expressions of TLR4, MyD88, NF-κB, and ICAM-1 were significantly downregulated. These results indicated that the mechanism of QGYD restoring LEV susceptibility to MDR PA was related to its regulation of inflammatory cytokines and the TLR4/MyD88/NF-κB signaling pathway, which provides theoretical support for the clinical application of QGYD combined with LEV therapy to MDR PA infection.

scholarly journals Post-antibiotic era in hemodialysis? Two case reports of simultaneous colonization and bacteremia by multidrug-resistant bacteria

2020 ◽  
Author(s):  
Johanna M. Vanegas ◽  
Lorena Salazar-Ospina ◽  
Gustavo A. Roncancio ◽  
Julián Builes ◽  
Judy Natalia Jiménez
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Case Reports ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Control Measures ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Carbapenem Resistant

ABSTRACT The emergence of resistance mechanisms not only limits the therapeutic options for common bacterial infections but also worsens the prognosis in patients who have conditions that increase the risk of bacterial infections. Thus, the effectiveness of important medical advances that seek to improve the quality of life of patients with chronic diseases is threatened. We report the simultaneous colonization and bacteremia by multidrug-resistant bacteria in two hemodialysis patients. The first patient was colonized by carbapenem- and colistin-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). The patient had a bacteremia by MRSA, and molecular typing methods confirmed the colonizing isolate was the same strain that caused infection. The second case is of a patient colonized by extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli and carbapenem-resistant Pseudomonas aeruginosa. During the follow-up period, the patient presented three episodes of bacteremia, one of these caused by ESBL-producing E. coli. Molecular methods confirmed colonization by the same clone of ESBL-producing E. coli at two time points, but with a different genetic pattern to the strain isolated from the blood culture. Colonization by multidrug-resistant bacteria allows not only the spread of these microorganisms, but also increases the subsequent risk of infections with limited treatments options. In addition to infection control measures, it is important to establish policies for the prudent use of antibiotics in dialysis units.

Identification of specific modules and hub genes associated with the progression of gastric cancer

2019 ◽  
Vol 40 (10) ◽  
pp. 1269-1277 ◽  
Author(s):  
Congcong Gong ◽  
Yang Hu ◽  
Mao Zhou ◽  
Maojin Yao ◽  
Zhengxiang Ning ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Cancer Progression ◽  
Messenger Rna ◽  
Large Scale ◽  
Early Stage ◽  
Expression Profiles ◽  
High Morbidity ◽  
Hub Genes ◽  
Micro Rnas

Abstract Gastric cancer (GC) has high morbidity and mortality rates worldwide. Abundant literature has reported several individual genes and their related pathways intimately involved in tumor progression. However, little is known about GC progression at the gene network level. Therefore, understanding the underlying mechanisms of pathological transition from early stage to late stage is urgently needed. This study aims to identify potential vital genes and modules involved in the progression of GC. To understand the gene regulatory network of GC progression, we analyzed micro RNAs and messenger RNA s expression profiles by using a couple of bioinformatics tools. miR-205 was identified by differentially expressed analysis and was further confirmed through using multiple kernel learning-based Kronecker regularized least squares. Using weighted gene co-expression network analysis, the gastric cancer progression-related module, which has the highest correlation value with cancer progression, was obtained. Kyoto Encyclopedia of Genes and Genomes pathways and biological processes of the GCPR module genes were related to cell adhesion. Meanwhile, large-scale genes of GCPR module were found to be targeted by miR-205, including two hub genes SORBS1 and LPAR1. In brief, through multiple analytical methods, we found that miR-205 and the GCPR module play critical roles in GC progression. In addition, miR-205 might maintain cell adhesion by regulating SORBS1 and LPAR1. To screen the potential drug candidates, the gene expression profile of the GCPR module was mapped connectivity map (Cmap), and the mTOR inhibitor (Sirolimus) was found to be the most promising candidate. We further confirmed that Sirolimus can suppress cell proliferation of GC cell in vitro.

scholarly journals Resistance Evolution against Phage Combinations Depends on the Timing and Order of Exposure

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Rosanna C. T. Wright ◽  
Ville-Petri Friman ◽  
Margaret C. M. Smith ◽  
Michael A. Brockhurst
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Fitness Costs ◽  
Evolutionary Trajectory ◽  
Promising Alternative ◽  
Content Type ◽  
Resistance Evolution

ABSTRACTPhage therapy is a promising alternative to chemotherapeutic antibiotics for the treatment of bacterial infections. However, despite recent clinical uses of combinations of phages to treat multidrug-resistant infections, a mechanistic understanding of how bacteria evolve resistance against multiple phages is lacking, limiting our ability to deploy phage combinations optimally. Here, we show, usingPseudomonas aeruginosaand pairs of phages targeting shared or distinct surface receptors, that the timing and order of phage exposure determine the strength, cost, and mutational basis of resistance. Whereas sequential exposure allowed bacteria to acquire multiple resistance mutations effective against both phages, this evolutionary trajectory was prevented by simultaneous exposure, resulting in quantitatively weaker resistance. The order of phage exposure determined the fitness costs of sequential resistance, such that certain sequential orders imposed much higher fitness costs than the same phage pair in the reverse order. Together, these data suggest that phage combinations can be optimized to limit the strength of evolved resistances while maximizing their associated fitness costs to promote the long-term efficacy of phage therapy.IMPORTANCEGlobally rising rates of antibiotic resistance have renewed interest in phage therapy where combinations of phages have been successfully used to treat multidrug-resistant infections. To optimize phage therapy, we first need to understand how bacteria evolve resistance against combinations of multiple phages. Here, we use simple laboratory experiments and genome sequencing to show that the timing and order of phage exposure determine the strength, cost, and mutational basis of resistance evolution in the opportunistic pathogenPseudomonas aeruginosa. These findings suggest that phage combinations can be optimized to limit the emergence and persistence of resistance, thereby promoting the long-term usefulness of phage therapy.

scholarly journals Tasked with a Challenging Objective: Why Do Neutrophils Fail to Battle Pseudomonas aeruginosa Biofilms

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 283 ◽  
Author(s):  
Jennifer Geddes-McAlister ◽  
Abirami Kugadas ◽  
Mihaela Gadjeva
Keyword(s):  
United States ◽  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Bacterial Biofilms ◽  
Spectroscopy Analysis ◽  
Mass Spectroscopy Analysis ◽  
Novel Therapeutic

Multidrug-resistant (MDR) bacterial infections are a leading cause of mortality, affecting approximately 250,000 people in Canada and over 2 million people in the United States, annually. The lack of efficacy of antibiotic-based treatments is often caused by inability of the drug to penetrate bacterial biofilms in sufficient concentrations, posing a major therapeutic challenge. Here, we review the most recent information about the architecture of Pseudomonas aeruginosa biofilms in vivo and describe how advances in imaging and mass spectroscopy analysis bring about novel therapeutic options and challenge existing dogmas.

scholarly journals Bacterial Nosocomial Infections: Multidrug Resistance as a Trigger for the Development of Novel Antimicrobials

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 942
Author(s):  
Sílvia A. Sousa ◽  
Joana R. Feliciano ◽  
Tiago Pita ◽  
Catarina F. Soeiro ◽  
Beatriz L. Mendes ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Nosocomial Infections ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Healthcare Systems ◽  
High Morbidity ◽  
Therapeutic Approaches ◽  
New Compounds ◽  
Novel Therapeutic

Nosocomial bacterial infections are associated with high morbidity and mortality, posing a huge burden to healthcare systems worldwide. The ongoing COVID-19 pandemic, with the raised hospitalization of patients and the increased use of antimicrobial agents, boosted the emergence of difficult-to-treat multidrug-resistant (MDR) bacteria in hospital settings. Therefore, current available antibiotic treatments often have limited or no efficacy against nosocomial bacterial infections, and novel therapeutic approaches need to be considered. In this review, we analyze current antibacterial alternatives under investigation, focusing on metal-based complexes, antimicrobial peptides, and antisense antimicrobial therapeutics. The association of new compounds with older, commercially available antibiotics and the repurposing of existing drugs are also revised in this work.

scholarly journals Comprehensive Analysis of Differentially Expressed lncRNA, circRNA and mRNA and Their ceRNA Networks in Mice With Severe Acute Pancreatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Bing Wang ◽  
Jun Wu ◽  
Qilin Huang ◽  
Xiaohui Yuan ◽  
Yi Yang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Signaling Pathway ◽  
Severe Acute Pancreatitis ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Control Group ◽  
Calcium Signal ◽  
High Morbidity ◽  
Apoptosis Pathway

Severe acute pancreatitis (SAP) is an acute digestive system disease with high morbidity mortality and hospitalization rate worldwide, due to various causes and unknown pathogenesis. In recent years, a large number of studies have confirmed that non-coding RNAs (ncRNAs) play an important role in many cellular processes and disease occurrence. However, the underlying mechanisms based on the function of ncRNAs, including long noncoding RNA (lncRNA) and circular RNA (circRNA), in SAP remain unclear. In this study, we performed high-throughput sequencing on the pancreatic tissues of three normal mice and three SAP mice for the first time to describe and analyze the expression profiles of ncRNAs, including lncRNA and circRNA. Our results identified that 49 lncRNAs, 56 circRNAs and 1,194 mRNAs were differentially expressed in the SAP group, compared with the control group. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed lncRNAs and circRNAs, and found that the functions of the parental genes are enriched in the calcium-regulated signaling pathway, NF-κB signaling pathway, autophagy and protein digestion and absorption processes, which are closely related to the central events in pathogenesis of SAP. We also constructed lncRNA/circRNA-miRNA-mRNA networks to further explore their underlying mechanism and possible relationships in SAP. We found that in the competitive endogenous RNA (ceRNA) networks, differentially expressed lncRNAs and circRNAs are mainly involved in the apoptosis pathway and calcium signal transduction pathway. In conclusion, we found that lncRNAs and circRNAs play an important role in the pathogenesis of SAP, which may provide new insights in further exploring the pathogenesis of SAP and seek new targets for SAP.

scholarly journals Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Jin ◽  
Lei Li ◽  
Yuehan Hao ◽  
Ling Tang ◽  
Yuye Wang ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Network Analysis ◽  
Intracerebral Hemorrhage ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Cell Apoptosis ◽  
Expression Profiles ◽  
Control Group ◽  
High Morbidity ◽  
Blood Draw

PurposeIntracerebral hemorrhage (ICH) is a serious public health hazard due to its high morbidity, disability, and mortality. Currently, the exact molecular mechanisms of ICH are unknown. We tried to identify the ICH-related candidate blood messenger RNA (mRNA) biomarkers by microarray analysis and weighted gene co-expression network analysis (WGCNA).Materials and MethodsWe collected the blood samples from patients with ICH (n = 4) and from vascular risk factor (VRF) controls (n = 4) and analyzed the mRNA expression profiles by competitive endogenous RNA (ceRNA) microarray. Differentially expressed genes (DEGs) were identified and then a weighted gene co-expression network was constructed. Modules with clinical significance were distinguished. Then, we downloaded two Gene Expression Omnibus (GEO) datasets (GSE24265 and GSE125512). Candidate mRNAs were identified by taking the intersection of the DEGs in our microarray, the interesting genes in the key module, and the DEGs in GSE24265. Functional analysis involving Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and construction of a protein–protein interaction (PPI) network were conducted.ResultsA total of 340 DEGs in our microarray were identified between the ICH group and the control group. Among the eight gene modules established by WGCNA, the yellow module containing 191 genes was the most strongly associated with ICH. Four candidate mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) were identified. In the early stage of ICH (within 24 h), C3AR1, PAWR, and ARNTL2 were highly expressed in the perihematomal tissue, but with low expressions in peripheral blood; in the late stage (72 h after the first blood draw), an obvious upward trend of C3AR1 and PAWR in peripheral blood was seen. Functional analysis showed that candidate mRNAs were concerned with multiple pathways, such as the Wnt signaling pathway and calcium signaling pathway. They might affect the process of ICH through neuroinflammation, cell apoptosis, and pyroptosis.ConclusionWe identified four candidate blood mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) related to ICH. They showed different expression patterns in peripheral blood and perihematomal tissues and changed with time. They might play important roles in ICH through neuroinflammation, cell apoptosis, and pyroptosis and might shed new light to novel biomarkers or therapeutic targets in ICH.

scholarly journals Surveillance of bacteria Pseudomonas aeruginosa and MRSA associated with acute suppurative otitis media (ASOM)

2017 ◽  
Vol 6 (1) ◽  
pp. 69 ◽  
Author(s):  
Kundan K. Sahu ◽  
Siba N. Rath ◽  
Rabindra N. Padhy ◽  
Rajashree Panigrahi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Otitis Media ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Coagulase Negative Staphylococcus ◽  
Bacterial Strains ◽  
Suppurative Otitis Media ◽  
Intracranial Complications ◽  
Susceptibility Rate ◽  
Middle Ear Cleft

Background: Otitis media particularly with suppuration is a critical disease-causing perforation of the tympanic membrane associated with changes of the mucoperiosteum of the middle ear cleft. This surveillance includes isolation and antibiotic profiles of causative bacteria from ear discharges of patients in 3years attending outpatients of a hospital.Methods: Bacterial strains were grown in suitable media and were subjected to antibiotic profiling by the Kirby-Bauer’s method with most antibiotics of the day.Results: In total there were 1164 colonies with 1043 bacterial and 121 fungal isolates from 1230 ear discharge samples. Among 371 Pseudomonas aeruginosa isolates, tobramycin 30 µg/disk had the highest susceptibility rate as 93.2%, followed by ceftazidime 30µg/disk 91.5% and amikacin 10µg/disk 64.4%. From 359 Staphylococcus isolates, there were 236 coagulase negative Staphylococcus (CONS) + methicillin sensitive S. aureus (MSSA) and 123 methicillin resistant S. aureus (MRSA). Staphylococcus including MRSA isolates were most susceptibility to cloxacillin 15µg/disk 95.2%, followed by erythromycin 15µg/disk 83.3% and gentamicin 30µg/disk 78.5%. Of 1164, 49 patients presented post aural abscess, 12 patients had intracranial complications, 9 patients had facial palsy and 3 patients had labyrinthitis.Conclusions: Isolated bacteria, P. aeruginosa and MRSA were multidrug resistant. P. aeruginosa was most common followed by S. aureus. More than 90% P. aeruginosa and 90% S. aureus isolates were sensitive to tobramycin 30 µg/disk and cloxacillin 30 µg/disk, respectively. Therefore, these two antibiotics may be included in the formulary regimen to overcome bacterial infections involved in ASOM.

scholarly journals Ceftolozane-Tazobactam Activity against Pseudomonas aeruginosa Clinical Isolates from U.S. Hospitals: Report from the PACTS Antimicrobial Surveillance Program, 2012 to 2015

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Dee Shortridge ◽  
Mariana Castanheira ◽  
Michael A. Pfaller ◽  
Robert K. Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Drug Resistant ◽  
Content Type ◽  
Microdilution Method ◽  
Antimicrobial Surveillance ◽  
Broth Microdilution Method

ABSTRACT The activity of ceftolozane-tazobactam was compared to the activities of 7 antimicrobials against 3,851 Pseudomonas aeruginosa isolates collected from 32 U.S. hospitals in the Program to Assess Ceftolozane-Tazobactam Susceptibility from 2012 to 2015. Ceftolozane-tazobactam and comparator susceptibilities were determined using the CLSI broth microdilution method at a central monitoring laboratory. For ceftolozane-tazobactam, 97.0% of the isolates were susceptible. Susceptibilities of the other antibacterials tested were: amikacin, 96.9%; cefepime, 85.9%; ceftazidime, 85.1%; colistin, 99.2%; levofloxacin, 76.6%; meropenem, 81.8%; and piperacillin-tazobactam, 80.4%. Of the 699 (18.1%) meropenem-nonsusceptible P. aeruginosa isolates, 87.6% were susceptible to ceftolozane-tazobactam. Six hundred seven isolates (15.8%) were classified as multidrug resistant (MDR), and 363 (9.4%) were classified as extensively drug resistant (XDR). Only 1 isolate was considered pandrug resistant, which was resistant to all tested agents, including colistin. Of the 607 MDR isolates, 84.9% were ceftolozane-tazobactam susceptible, and 76.9% of XDR isolates were ceftolozane-tazobactam susceptible. In vitro activity against drug-resistant P. aeruginosa indicates ceftolozane-tazobactam may be an important agent in treating serious bacterial infections.

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