Klebsiella pneumoniae in gastrointestinal tract and pyogenic liver abscess.
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ABSTRACT:
SUBMITTER: Fung CP
PROVIDER: S-EPMC3414011 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K(1) (-) O(1)) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain.
| S-EPMC3299736 | biostudies-literature
Project description:BACKGROUND: Community-acquired pyogenic liver abscess (PLA) complicated with meningitis and endophthalmitis caused by Klebsiella pneumoniae is an emerging infectious disease. To investigate the mechanisms and effects of biofilm formation of K. pneumoniae causing PLA, microtiter plate assays were used to determine the levels of biofilm formed by K. pneumoniae clinical isolates and to screen for biofilm-altered mutants from a transposon mutant library of a K. pneumoniae PLA-associated strain. METHODOLOGY/PRINCIPAL FINDINGS: The biofilm formation of K. pneumoniae was examined by microtiter plate assay. Higher levels of biofilm formation were demonstrated by K. pneumoniae strains associated with PLA. A total of 23 biofilm-decreased mutants and 4 biofilm-increased mutants were identified. Among these mutants, a biofilm-decreased treC mutant displayed less mucoviscosity and produced less capsular polysaccharide (CPS), whereas a biofilm-increased sugE mutant displayed higher mucoviscosity and produced more CPS. The biofilm phenotypes of treC and sugE mutants also were confirmed by glass slide culture. Deletion of treC, which encodes trehalose-6-phosphate hydrolase, impaired bacterial trehalose utilization. Addition of glucose to the culture medium restored the capsule production and biofilm formation in the treC mutant. Transcriptional profile analysis suggested that the increase of CPS production in ?sugE may reflect elevated cps gene expression (upregulated through rmpA) in combination with increased treC expression. In vivo competition assays demonstrated that the treC mutant strain was attenuated in competitiveness during intragastric infection in mice. CONCLUSIONS/SIGNIFICANCE: Genes important for biofilm formation by K. pneumoniae PLA strain were identified using an in vitro assay. Among the identified genes, treC and sugE affect biofilm formation by modulating CPS production. The importance of treC in gastrointestinal tract colonization suggests that biofilm formation contributes to the establishment and persistence of K. pneumoniae infection.
| S-EPMC3155550 | biostudies-literature
Project description:BACKGROUND: Klebsiella pneumoniae has emerged worldwide as a cause of pyogenic liver abscess (PLA) often complicated by meningitis and endophthalmitis. Early detection of this infectious disease will improve its clinical outcome. Therefore, we tried to isolate immunodominant proteins secreted by K. pneumoniae strains causing PLA. RESULTS: The secreted proteins of the NTUH-K2044 strain were separated by two-dimensional electrophoresis and then immunoblotted using convalescent sera from patients with K. pneumoniae PLA. A ~30-kDa immunodominant protein was then identified. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed an open reading frame (KP1_p307) located on the pK2044 plasmid and bioinformatic analysis identified this protein as a signal peptide of unknown function. The KP1_p307 gene was more prevalent in PLA strains and capsular type K1/K2 strains, but disruption of this gene in NTUH-K2044 strain did not decrease virulence in mice. Ten of fourteen (71%) sera from patients with K. pneumoniae PLA were immunoreactive with the recombinant KP1_p307 protein. Seroconversion demonstrated by a rise in serum titer in serial serum samples confirmed that antibodies against the KP1_p307 protein were elicited after infection. CONCLUSIONS: The KP1_p307 protein could be used as an antigen for early serodiagnosis of K. pneumoniae PLA, particularly in K1/K2 PLA strains.
| S-EPMC4280002 | biostudies-literature
Project description:ObjectiveTo explore why serotype K2 accounts for a stable share in Klebsiella pneumoniae from pyogenic liver abscess (PLA).MethodsTotally 15 K2 K. pneumoniae strains from PLA, 21 K2 from non-PLA, and 31 K1 from PLA were collected from China. Sequence typing, molecular serotyping, regular PCR, and Galleria mellonella lethality were performed. A total of 12 virulence genes were detected: peg-344, allS, p-rmpA, p-rmpA2, c-rmpA, fimH, mrkD, iucA, iroN, irp2, entB, and wzi. The differences between K2 K. pneumoniae strains from PLA and non-PLA were investigated along with K1 ones.ResultsSignificant differences were found between K2 strains from PLA and non-PLA for the rates of virulence genes peg-344 and iucA. The latter group also showed more diverse sequence types than the former. Significant differences were only found for virulence genes allS and irp2 between K1 and K2 strains from PLA. Based on the equal virulence factors backgrounds other than serotypes, K2 strain is more virulent than K1 as G. mellonella lethality confirmed. Gene p-rmpA only brings equal virulence to p-rmpA plus p-rmpA2 in K2 strain.ConclusionBased on the same virulence factors backgrounds except serotypes, K2 K. pneumoniae is more virulent than K1 from PLA, which provides a survival advantage to maintain a stable share.
| S-EPMC10825582 | biostudies-literature
Project description:While Klebsiella pneumoniae is a common cause of nosocomial and community-acquired infections, including pneumonia and pyogenic liver abscess, little is known about the population structure of this bacterium. In this study, we investigated the prevalence and molecular characteristics of K. pneumoniae isolates from carriers, pyogenic liver abscess patients, and pneumonia patients, and genomic and phenotypic assays were used to determine the differences among the isolates. A total of 232 K. pneumoniae isolates were subtyped into 74 sequence types (STs). The isolates from different sources had their own STs, and the predominant subtypes in liver abscess and pneumonia patients were ST23 and ST11, respectively. Pangenome analysis also distinguished three phylogroups that were consistent with the isolate sources. The isolates collected from liver abscess patients carried significantly more virulence factors, and those from pneumonia patients harbored significantly more resistance genes and replicons. Almost all isolate STs (93/97 [95.88%]) from liver abscesses strongly correlated with the virulence factor salmochelin, while most pneumonia isolate STs (52/53 [98.11%]) from pneumonia did not correlate with salmochelin. The isolates collected from liver abscesses showed higher virulence in the cytotoxicity and mouse models. These data provide genomic support for the proposal that isolates collected from carriers, liver abscess patients, and pneumonia patients have distinct genomic features. Isolates from the different sources are largely nonoverlapping, suggesting that different patients may be infected via different sources. Further studies on the pathogenic mechanisms of salmochelin and other virulence factors will be required. IMPORTANCE While Klebsiella pneumoniae is a common cause of nosocomial and community-acquired infections, including pneumonia and pyogenic liver abscess, little is known about the population structure of this bacterium. We collected 232 isolates from carriers, pyogenic liver abscess patients, and pneumonia patients, and the isolates from different sources had their own sequence types. Pangenome analysis also distinguished three phylogroups that were consistent with the isolate sources. The isolates collected from liver abscess patients carried significantly more virulence factors, and those from pneumonia patients harbored significantly more resistance genes and replicons. Besides, there was a strong link between salmochelin and liver abscess. The isolates collected from liver abscesses also showed higher virulence in the cytotoxicity and mouse models. Isolates collected from different sources have distinct genomic features, suggesting that different patients may be infected via different sources.
| S-EPMC9045331 | biostudies-literature
Project description:Pyogenic liver abscess has a variable clinical presentation. Its management requires input from several disciplines and is often coordinated by a gastroenterologist. This review examines demographics, clinical presentation, aetiology, diagnosis and prognosis; a suggested management approach, including antibiotic selection, radiological intervention and indications for surgery, is offered from a physician's perspective.
| S-EPMC5369710 | biostudies-other
Project description:Taiwan has witnessed an emerging syndrome of liver abscess caused by Klebsiella pneumoniae carrying the magA gene required for exopolysaccharide web biosynthesis. We report a patient transferred from Alaska to Washington State with a magA(+) K. pneumoniae liver abscess and describe a simple approach for recognition of these hypervirulent strains.
| S-EPMC548117 | biostudies-literature
Project description:The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent Klebsiella pneumoniae (hvKP), the causative agent of KLA. DNA and myeloperoxidase levels were elevated in the plasma of KLA patients compared to uninfected individuals indicating neutrophil activation, but diabetic status had no effect on these neutrophil extracellular trap (NET) biomarkers in both subject groups. Clinical hvKP isolates universally stimulated KLA patient neutrophils to produce NETs ex vivo, regardless of host diabetic status. Ability of representative capsule types (K1, K2, and non-K1/K2 strains) to survive intra- and extra-cellular killing by type 2 DM and healthy neutrophils was subsequently examined. Key findings were: (1) type 2 DM and healthy neutrophils exhibited comparable total, phagocytic, and NETs killing against hvKP, (2) phagocytic and NETs killing were equally effective against hvKP, and (3) hypermucoviscous K1 and K2 strains were more resistant to total, phagocytic, and NETs killing compared to the non-mucoviscous, non-K1/K2 strain. The cytokine response and intracellular killing ability of type 2 DM as well as healthy PBMCs upon encounter with the different capsule types was also examined. Notably, the IL-12-IFNγ axis and its downstream chemokines MIG, IP-10, and RANTES were produced at slightly lower levels by type 2 DM PBMCs than healthy PBMCs in response to representative K1 and non-K1/K2 strains. Furthermore, type 2 DM PBMCs have a mild defect in its ability to control hvKP replication relative to healthy PBMCs. In summary, our work demonstrates that type 2 DM does not overtly impact neutrophil intra- and extra-cellular killing of hvKP, but may influence cytokine/chemokine production and intracellular killing by PBMCs.
| S-EPMC5594087 | biostudies-literature
Project description:BACKGROUND: Commensurate with the advances in diagnostic and therapeutic radiology in the past two decades, percutaneous needle aspiration and catheter drainage have replaced open operation as the first choice of treatment for both single and multiple pyogenic liver abscesses. There has been little written on the place of surgical resection in the treatment of pyogenic liver abscess due to underlying hepatobiliary pathology or after failure of non-operative management. METHODS: The medical records of patients who underwent resection for pyogenic liver abscess over a 15-year period were retrospectively reviewed. The demographics, time from onset of symptoms to medical treatment and operation, site of abscess, organisms cultured, aetiology, reason for operation, type of resection and outcome were analysed. There were 49 patients in whom the abscesses were either single (19), single but multiloculated (11) or multiple (19). The median time from onset of symptoms to medical treatment was 21 days and from treatment to operation was 12 days. The indications for operation were underlying hepatobiliary pathology in 20% and failed non-operative treatment in 76%. Two patients presented with peritonitis from a ruptured abscess. RESULTS: The resections performed were anatomic (44) and non-anatomic (5). No patient suffered a recurrent abscess or required surgical or radiological intervention for any abdominal collection. Antibiotics were ceased within 5 days of operation in all but one patient. The median postoperative stay was 10 days. There were two deaths (4%), both following rupture of the abscess. DISCUSSION: Except for an initial presentation with intraperitoneal rupture and, possibly, cases of hepatobiliary pathology causing multiple abscesses above an obstructed duct system that cannot be negotiated non-operatively, primary surgical treatment of pyogenic liver abscess is not indicated. Non-operative management with antibiotics and percutaneous aspiration/drainage will be successful in most patients. If non-operative treatment fails, different physical characteristics of the abscesses are likely to be present and partial hepatectomy of the involved portion of liver is good treatment when performed by an experienced surgeon.
| S-EPMC2020568 | biostudies-other
Project description:Hypervirulent variants of Klebsiella pneumoniae (hvKp) that cause invasive community-acquired pyogenic liver abscess (PLA) have emerged globally. Little is known about the virulence determinants associated with hvKp, except for the virulence genes rmpA/A2 and siderophores (iroBCD/iucABCD) carried by the pK2044-like large virulence plasmid. Here, we collected most recent clinical isolates of hvKp from PLA samples in China, and performed clinical, molecular, and genomic sequencing analyses. We found that 90.9% (40/44) of the pathogens causing PLA were K. pneumoniae. Among the 40 LA-Kp, K1 (62.5%), and K2 (17.5%) were the dominant serotypes, and ST23 (47.5%) was the major sequence type. S1-PFGE analyses demonstrated that although 77.5% (31/40) of the LA-Kp isolates harbored a single large virulence plasmid varied in size, 5 (12.5%) isolates had no plasmid and 4 (10%) had two or three plasmids. Whole genome sequencing and comparative analysis of 3 LA-Kp and 3 non-LA-Kp identified 133 genes present only in LA-Kp. Further, large scale screening of the 133 genes in 45 LA-Kp and 103 non-LA-Kp genome sequences from public databases identified 30 genes that were highly associated with LA-Kp, including iroBCD, iucABCD and rmpA/A2 and 21 new genes. Then, these 21 new genes were analyzed in 40 LA-Kp and 86 non-LA-Kp clinical isolates collected in this study by PCR, showing that new genes were present 80-100% among LA-Kp isolates while 2-11% in K. pneumoniae isolates from sputum and urine. Several of the 21 genes have been proposed as virulence factors in other bacteria, such as the gene encoding SAM-dependent methyltransferase and pagO which protects bacteria from phagocytosis. Taken together, these genes are likely new virulence factors contributing to the hypervirulence phenotype of hvKp, and may deepen our understanding of virulence mechanism of hvKp.
| S-EPMC5126061 | biostudies-literature