scholarly journals TREM-1 Promotes Survival during Klebsiella pneumoniae Liver Abscess in Mice

2014 ◽  
Vol 82 (3) ◽  
pp. 1335-1342 ◽  
Author(s):  
Yi-Tsung Lin ◽  
Kai-Yu Tseng ◽  
Yi-Chen Yeh ◽  
Fu-Chen Yang ◽  
Chang-Phone Fung ◽  
...  
Keyword(s):  
Small Intestine ◽  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Survival Rates ◽  
Bacterial Clearance ◽  
Mesenteric Lymph Nodes ◽  
Content Type ◽  
Cytokine Levels ◽  
Peptide Expression ◽  
Antimicrobial Peptide Expression

ABSTRACTKlebsiella pneumoniaeliver abscess (KPLA) is prevalent in East Asia. Liver abscess can develop after translocation ofK. pneumoniaefrom a patient's bowel into the liver via the portal circulation. TREM-1 (triggeringreceptorexpressed onmyeloid cells1) amplifies inflammatory signaling during infection, but its role in KPLA is poorly understood. We used an animal study to characterize the role of TREM-1 in KPLA. We compared survival rates, bacterial burdens in tissues, inflammatory cytokine levels, and histology findings between wild-type andTrem-1knockout (KO) mice after oral inoculation of capsular type K1K. pneumoniae. Translocation ofK. pneumoniaeto mesenteric lymph nodes and liver was examined, and intestinal permeability, antimicrobial peptide expression, and the clearance ofK. pneumoniaein the small intestine were determined. In the absence of TREM-1, KPLA model mice showed increasedK. pneumoniaedissemination, enhanced liver and systemic inflammation, and reduced survival. Impaired bacterial clearance in the small intestine causes enhancedK. pneumoniaetranslocation, which rendersTrem-1KO mice more susceptible toK. pneumoniaeoral infection. In conclusion, TREM-1-mediated bacterial clearance in the small intestine is an important immune response againstK. pneumoniae. TREM-1 deficiency enhancesK. pneumoniaetranslocation in the small intestine and increases mortality rates in mice with KPLA.

scholarly journals Loss of Hypermucoviscosity and Increased Fitness Cost in Colistin-Resistant Klebsiella pneumoniae Sequence Type 23 Strains

2015 ◽  
Vol 59 (11) ◽  
pp. 6763-6773 ◽  
Author(s):  
Myung-Jin Choi ◽  
Kwan Soo Ko
Keyword(s):  
Klebsiella Pneumoniae ◽  
Lipid A ◽  
Survival Rates ◽  
Sequence Type ◽  
Fitness Cost ◽  
Colistin Resistance ◽  
Content Type ◽  
Expression Levels ◽  
Maldi Tof ◽  
Resistant Mutants

ABSTRACTIn this study, we investigated the effects of colistin resistance on virulence and fitness in hypermucoviscous (HV)Klebsiella pneumoniaesequence type 23 (ST23) strains. Colistin-resistant mutants were developed from three colistin-susceptible HVK. pneumoniaeST23 strains. The lipid A structures of strains were analyzed by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. Changes in HV were investigated using the string test, and extracellular polysaccharide production was quantified. The expression levels of thephoQ,pmrD,pmrB,pbgP,magA, and p-rmpA2genes, serum resistance, and biofilm-forming activity were determined. The fitness of colistin-resistant mutants compared to that of the parental strains was examined by determining the competitive index (CI). The colistin-resistant mutants exhibited reduced HV, which was accompanied by decreased formation of capsular polysaccharides (CPS) and reduced expression of genes (magAand p-rmpA2). While there was enhanced expression ofpmrDandpbgPin all colistin-resistant derivatives, there were differences in the expression levels ofphoQandpmrBbetween strains. MALDI-TOF analysis detected the addition of aminoarabinose or palmitate to the lipid A moiety of lipopolysaccharide in the colistin-resistant derivatives. In addition, survival rates in the presence of normal human serum were decreased in the mutant strains, and CI values (0.01 to 0.19) indicated significant fitness defects in the colistin-resistant derivatives compared to the respective parental strains. In hypervirulent HVK. pneumoniaestrains, the acquisition of colistin resistance was accompanied by reduced CPS production, impaired virulence, and a significant fitness cost.

scholarly journals Antibody-Based Immunotherapy To Treat and Prevent Infection with Hypervirulent Klebsiella pneumoniae

2016 ◽  
Vol 24 (1) ◽  
Author(s):  
Elizabeth Diago-Navarro ◽  
Isabel Calatayud-Baselga ◽  
Donglei Sun ◽  
Camille Khairallah ◽  
Inderjit Mann ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Intravital Microscopy ◽  
Protective Antigen ◽  
Protective Efficacy ◽  
Mesenteric Lymph Nodes ◽  
Content Type ◽  
Anthrax Protective Antigen

ABSTRACT Hypervirulent Klebsiella pneumoniae (hvKp) strains are predicted to become a major threat in Asia if antibiotic resistance continues to spread. Anticapsular antibodies (Abs) were developed because disseminated infections caused by hvKp are associated with significant morbidity and mortality, even with antibiotic-sensitive strains. K1-serotype polysaccharide capsules (K1-CPS) are expressed by the majority of hvKp strains. In this study, K1-CPS-specific IgG Abs were generated by conjugation of K1-CPS to immunogenic anthrax protective antigen (PA) protein. Opsonophagocytic efficacy was measured in vitro and in vivo by intravital microscopy in murine livers. In vivo protection was tested in murine models, including a novel model for dissemination in hvKp-colonized mice. Protective efficacy of monoclonal antibodies (MAbs) 4C5 (IgG1) and 19A10 (IgG3) was demonstrated both in murine sepsis and pulmonary infection. In hvKp-colonized mice, MAb treatment significantly decreased dissemination of hvKp from the gut to mesenteric lymph nodes and organs. Intravital microscopy confirmed efficient opsonophagocytosis and clearance of bacteria from the liver. In vitro studies demonstrate that MAbs work predominantly by promoting FcR-mediated phagocytosis but also indicate that MAbs enhance the release of neutrophil extracellular traps (NETs). In anticipation of increasing antibiotic resistance, we propose further development of these and other Klebsiella-specific MAbs for therapeutic use.

scholarly journals Identification of Capsular Types in Carbapenem-Resistant Klebsiella pneumoniae Strains bywzcSequencing and Implications for Capsule Depolymerase Treatment

2014 ◽  
Vol 59 (2) ◽  
pp. 1038-1047 ◽  
Author(s):  
Yi-Jiun Pan ◽  
Tzu-Lung Lin ◽  
Yi-Tsung Lin ◽  
Po-An Su ◽  
Chun-Tang Chen ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Vaccine Development ◽  
Survival Rates ◽  
Multidrug Resistant ◽  
Enzyme Treatment ◽  
Capsular Type ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Sequence Types

ABSTRACTKlebsiella pneumoniaeis an important human pathogen associated with a variety of diseases, and the prevalence of multidrug-resistantK. pneumoniae(MDRKP) is rapidly increasing. Here we determined the capsular types of 85 carbapenem-resistantK. pneumoniae(CRKP) strains bywzcsequencing and investigated the presence of carbapenemases and integrons among CRKP strains. Ten CRKP strains (12%) were positive for carbapenemase (imipenemase, 6/85 strains;K. pneumoniaecarbapenemase, 3/85 strains; Verona integron-encoded metallo-β-lactamase, 1/85 strains). Capsular type K64 accounted for 32 CRKP strains (38%), followed by K62 (13%), K24 (8%), KN2 (7%), and K28 (6%). Sequence types (STs) were determined by multilocus sequence typing (MLST), and the results indicated that ST11, which accounted for 47% of these CRKP strains (40/85 strains), was the major ST. We further isolated a K64-specific capsule depolymerase (K64dep), which could enhance serum and neutrophil killingin vitroand increase survival rates for K64K. pneumoniae-inoculated mice. The toxicity study demonstrated that mice treated with K64dep showed normal biochemical parameters and no significant histopathological changes of liver, kidney, and spleen, indicating that enzyme treatment did not cause toxicity in mice. Therefore, the findings of capsular type clustering among CRKP strains and effective treatment with capsule depolymerase for MDRKP infections are important for capsule-based vaccine development and therapy.

Infectivity of Hepatic Strain Klebsiella pneumoniae in Diabetic Mice

2005 ◽  
Vol 230 (10) ◽  
pp. 757-761 ◽  
Author(s):  
June Hsieh Wu ◽  
Cheng Gie Tsai
Keyword(s):  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Survival Rates ◽  
Bacterial Count ◽  
Enzyme Linked Immunosorbent Assay ◽  
Bacterial Suspension ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Tnf Α ◽  
Α Level

Besides urinary tract infection (UTI) and pneumonia, increased severe liver abscesses caused by Klebsiella pneumoniae (KP), especially in diabetic patients, have been observed in infections acquired in hospitals. This indicates that different KP strains with higher virulence have emerged in recent years. Our goal was to investigate the infectivity of KP isolates in mice from liver abscess or UTI patients. Mice were injected with streptozotocin to induce diabetes. Male ICR mice were infected with KpU1 (UTI strain CG3 for survival experiment only) and KpL1 (liver abscess strain CG5) by tail-vein injection of 5 × 104 colony-forming units (CFU) bacterial suspension. The mice survival rates, cytokine level by enzyme-linked immunosorbent assay (ELISA), and bacterial presence in liver tissue by Giemsa stain were examined. The survival rates for the KpL1-infected animals were 28% and 0% in normal and diabetic groups, respectively, whereas, for the KpU1-infected mice, the rates were 100% and 75% during a 30-day observation. Nonsurviving KpL1-infected mice showed >105 bacteria/ml blood and the bacteria appeared in the liver sinus area and inside liver cells. The KpL1-infected mice showed a tendency to increase the blood interleukin 1β (IL-1β) level in both nondiabetic and diabetic groups, whereas the tumor necrosis factor-Α (TNF-Α) level was significantly decreased in the KpL1-infected diabetic mice (P = 0.002). In conclusion, the KP strain from liver abscess showed a greater virulence in mice than the KP from UTI and was more virulent in diabetic than in nondiabetic mice. The infection with KP from liver abscess significantly decreased the blood TNF-Α level in diabetes mellitus (DM) mice and the blood IL-1β level tended to increase in both infected nondiabetic and diabetic groups. High blood bacterial count and appearance of bacteria in liver sinus and cells usually contribute to death of the animals.

scholarly journals Molecular and Clinical Characterization of Multidrug-Resistant and Hypervirulent Klebsiella pneumoniae Strains from Liver Abscess in Taiwan

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Yi-Tsung Lin ◽  
Yi-Hsiang Cheng ◽  
Chien Chuang ◽  
Sheng-Hua Chou ◽  
Wan-Hsin Liu ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Virulence Plasmid ◽  
Content Type ◽  
Sequence Types

ABSTRACT Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.

scholarly journals Transfer of CMY-2 Cephalosporinase from Escherichia coli to Virulent Klebsiella pneumoniae Causing a Recurrent Liver Abscess

2015 ◽  
Vol 59 (8) ◽  
pp. 5000-5002 ◽  
Author(s):  
Yi-Tsung Lin ◽  
Yi-Jiun Pan ◽  
Tzu-Lung Lin ◽  
Chang-Phone Fung ◽  
Jin-Town Wang
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Multidrug Resistant ◽  
Wild Type ◽  
Content Type ◽  
Resistant Phenotype ◽  
High Virulence ◽  
Successful Transfer ◽  
Conjugation Experiment

ABSTRACTA CMY-2-producing capsular type K2Klebsiella pneumoniaestrain (TVGHKP93) with multidrug resistance was isolated from a recurrent liver abscess in a patient who also carried a CMY-2-producingEscherichia colistrain (TVGHEC01) in the stool. TVGHKP93 retained its high virulence compared with that of the isogenic strain (TVGHKP60) with wild-type resistance from the first liver abscess. Our conjugation experiment showed the successful transfer of theblaCMY-2-carrying plasmid from TVGHEC01 into TVGHKP60. The transconjugant showed both high virulence and the multidrug-resistant phenotype, as did TVGHKP93.

scholarly journals High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

2016 ◽  
Vol 113 (40) ◽  
pp. E5934-E5943 ◽  
Author(s):  
Julie Tomas ◽  
Céline Mulet ◽  
Azadeh Saffarian ◽  
Jean-Baptiste Cavin ◽  
Robert Ducroc ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Small Intestine ◽  
Antimicrobial Peptide ◽  
Bacterial Colonization ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Peptide Expression ◽  
Antimicrobial Peptide Expression

Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum—which is usually described as free of bacteria—became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance ofErysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) andCandidatus arthromitus. A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed inPpar-γ–deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.

scholarly journals Efficacy of Intranasal Administration of the Recombinant Endolysin SAL200 in a Lethal MurineStaphylococcus aureusPneumonia Model

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Ji Yun Bae ◽  
Kang Il Jun ◽  
Chang Kyung Kang ◽  
Kyoung-Ho Song ◽  
Pyoeng Gyun Choe ◽  
...  
Keyword(s):  
Intranasal Administration ◽  
Survival Rates ◽  
Severe Pneumonia ◽  
Treated Group ◽  
Control Group ◽  
Content Type ◽  
Adjunct Treatment ◽  
Candidate Drug ◽  
Cytokine Levels ◽  
And Control

ABSTRACTSAL200 is derived from a phage endolysin and is a novel candidate drug for the treatment ofStaphylococcus aureusinfection. We investigated the efficacy of the recombinant endolysin SAL200 in a lethal murine pneumonia model. Lethal pneumonia was established by intranasally administering a methicillin-susceptible (Newman) or methicillin-resistant (LAC)S. aureusstrain into BALB/c mice. The mice were treated with a single intranasal administration of SAL200 or phosphate-buffered saline at 2 h afterS. aureusinfection. The survival rates were recorded until 60 h after the bacterial challenge. The bacterial loads in the lungs and blood, histopathology of lung tissues, and serum cytokine levels were evaluated following theS. aureuschallenge. The SAL200-treated group and control group exhibited 90% to 95% and 10% to 40% survival rates, respectively. The bacterial loads in the lungs of the SAL200-treated group were significantly lower by ∼10-fold than those of the control group as early as 1 h after treatment. Histopathologic recovery of pneumonia was observed in the SAL200-treated mice. The cytokine levels were comparable between groups. These results suggest that direct administration of SAL200 into the lungs could be a potential adjunct treatment against severe pneumonia caused byS. aureus.

Role of the Yersinia pseudotuberculosis Virulence Plasmid in Pathogen-Phagocyte Interactions in Mesenteric Lymph Nodes

EcoSal Plus ◽  
2021 ◽  
Author(s):  
James B. Bliska ◽  
Igor E. Brodsky ◽  
Joan Mecsas
Keyword(s):  
Small Intestine ◽  
Lymph Nodes ◽  
Family Member ◽  
Yersinia Pseudotuberculosis ◽  
Oral Route ◽  
Virulence Plasmid ◽  
Mesenteric Lymph Nodes ◽  
Content Type ◽  
Mesenteric Lymph

Yersinia pseudotuberculosis is an Enterobacteriaceae family member that is commonly transmitted by the fecal-oral route to cause infections. From the small intestine, Y. pseudotuberculosis can invade through Peyer’s patches and lymph vessels to infect the mesenteric lymph nodes (MLNs).

Peyer's patch-specificLactobacillus reuteristrains increase extracellular microbial DNA and antimicrobial peptide expression in the mouse small intestine

2018 ◽  
Vol 9 (5) ◽  
pp. 2989-2997 ◽  
Author(s):  
Ce Qi ◽  
Jin Sun ◽  
Ya Li ◽  
Min Gu ◽  
Tim Goulette ◽  
...  
Keyword(s):  
Small Intestine ◽  
Gut Microbiota ◽  
Antimicrobial Peptide ◽  
Extracellular Dna ◽  
Peyer’S Patch ◽  
Peyer's Patch ◽  
Mouse Small Intestine ◽  
Peptide Expression ◽  
Antimicrobial Peptide Expression ◽  
Microbial Dna

Peyer's patch-specificL. reuterialters gut microbiota, promotes the release of bacterial extracellular DNA and increases antibacterial peptide expression in the small intestine crypts of mice.

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