Revisiting the Importance of Virulence Determinant<i>magA</i>and Its Surrounding Genes in<i>Klebsiella pneumoniae</i>Causing Pyogenic Liver Abscesses: Exact Role in Serotype K1 Capsule Formation

Yeh, Kuo-Ming; Lin, Jung‐Chung; Yin, Fon-Yi; Fung, Chang-Phoné; Hung, Han-Chang; Siu, L. Kristopher; Chang, Feng–Yee

doi:10.1086/606010

Cited by 81 publications

(80 citation statements)

References 29 publications

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“…8,9 The serotyping was performed as previously described. 9 MLST was performed according to the Institute Pasteur scheme. Sequences of 7 housekeeping genes were obtained from isolates from liver abscess patients and carriers.…”

Section: Methodsmentioning

confidence: 99%

“…Plasmid pUT-kmy consists of an R6K origin of replication, an mobRP4 origin of transfer, and a kanamycin resistance cassette, 9 and was ligated with a sacB gene to generate plasmid pUT-KB to construct allelic exchange mutants. Plasmid pUT-KB is a suicide vector containing a counter-selection marker sacB that originates from Bacillus subtilis.…”

Section: Detection Of Virulence Determinants For Hypervirulent Strainmentioning

confidence: 99%

“…Single-crossover strains were selected from brilliant green containing inositol-nitrate-deoxycholate (BIND) plates supplemented with kanamycin (50 mg/ml), while the growth of non-K. pneumoniae strains was effectively suppressed on the BIND plates. 9 A kanamycin-resistant transconjugant was selected, and the insertion of p-galF, p-acidPPc, p-wzi, p-wza, p-wzb or p-wzc was verified via PCR. After incubation in 20 ml BHI for 6 hours in the absence of kanamycin at 37 C, the fully grown cultures were spread onto LB plates supplemented with 10% sucrose.…”

Section: Detection Of Virulence Determinants For Hypervirulent Strainmentioning

confidence: 99%

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Effect in virulence of switching conserved homologous capsular polysaccharide genes fromKlebsiella pneumoniaeserotype K1 into K20

et al. 2016

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The capsular polysaccharides in different serotypes of Klebsiella pneumoniae (KP) coded by the (CPS) gene cluster are characterized by a conserved and a hyper-variable region. We performed a virulence study by switching genes in the highly conserved region of the CPS cluster between strains. Six genes in the CPS conserved region in serotype K20, including galF, acidPPc, wzi, wza, wzb and wzc, were knocked out and replaced by the homologous genes from serotype K1. Compared to the parental K20 strain, the mutants showed a decline in lethality (LD 50 ) in mice from 10-fold to > 10 5 -fold and were categorized in terms of the effect on virulence as low (L) for galF and acidPPC, moderate (M) for wzi, and high (H) for wza, wzb and wzc. Although substituting the acidPPC gene from K1 for acidPPC in the K20 strain fully restored virulence, substitution with the wzi, wza, wzb or wzc homologs from K1 did not. The restoration with wzi from K1 led to a partial restoration of virulence, with the LD 50 in mice changing from 10 4 to 10 3 CFU . For the wza, wzb and wzc genes, Complementation of K20 wza, wzb and wzc from K1 resulted in varied degrees of lethality in mice. Variable improvement in serum killing and phagocytosis was observed when the knockout mutants were compared with the geneswitched strains. In conclusion, homologous genes for capsule synthesis failed to exhibit the same functionality when switched between serotypes and virulence was decreased in different degree in according to the genes' homology.

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Section: Methodsmentioning

confidence: 99%

Section: Detection Of Virulence Determinants For Hypervirulent Strainmentioning

confidence: 99%

Section: Detection Of Virulence Determinants For Hypervirulent Strainmentioning

confidence: 99%

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Effect in virulence of switching conserved homologous capsular polysaccharide genes fromKlebsiella pneumoniaeserotype K1 into K20

et al. 2016

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“…DK1 is a non-polar glycosyl transferase gene (rfbP) mutant derived from an STL43 strain in our previous study that proved to be an acapsular and non-mucoid mutant. 17 Gene clusters related to K1 capsule formation were sequenced and published in Genbank under accession number AY762939. 18 Virulence-associated magA, rmpA and aerobactin were confirmed repeatedly with specific, previously described primer sets for PCR identification (magA forward, 5 0 -CGTGCTCTT TACATCATTGC-3 0 , magA reverse, 5 0 -GCAATGGCCATTTG CGTTAC-3 0 ; rmpA forward, 5 0 -ACTGGCTACCTCTGCTT CA-3 0 , rmpA reverse, 5 0 -CTTGCATGAGCCATCTTTCA-3 0 ; aerobactin forward, 5 0 -GCATAGGCGGATACGAACAT-3 0 , aerobactin reverse, 5 0 -CACAGGGCAATTGCTTACCT-3 0 ).…”

Section: Materials and Methods Microorganismsmentioning

confidence: 99%

Immune response and pathophysiological features of Klebsiella pneumoniae liver abscesses in an animal model

Fung

Chang

Lin

et al. 2011

Laboratory Investigation

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Capsular serotypes K1 and K2, the rmpA gene (a regulator of the mucoid phenotype) and aerobactin from Klebsiella pneumoniae have been identified as the major virulence factors for pyogenic liver abscesses with high morbidity, mortality and severe complications. The pathological mechanisms remain unclear. In this study, we compared liver immune responses and pathological changes in response to different serotypes of K. pneumoniae infections. A mouse model was used to investigate cytokine and chemokine production, histopathology findings, phagocytic uptake and mortality induced by serotypespneumoniae serotypes K1 and K2 showed lower 50% lethal dose values and more phagocytic resistance to neutrophils than K62 and the DK1 mutant. In sequential liver samples, viable bacteria counts increased 3 h to 3 days after low-dose inoculation (o10 1 colony-forming unit (cfu)) with K1 and K2, while K62 and DK1 cleared rapidly and became undetectable even with high-dose inoculation (B2.9 Â 10 5 cfu). Time-dependent increases in cytokines and chemokines, including tumor necrosis factor-a, interleukin (IL)-1b, IL-6, IL-10, keratinocyte-derived chemokines and macrophage inflammatory protein-2, were observed in the serum and liver tissue of K1-and K2-infected mice, and severe disease progression manifesting as microabscesses was also identified. K62 and DK1 inoculation did not result in similar immune responses and histological changes. These findings illustrate the critical role of phagocytic resistance against innate immunological defense mechanisms as well as its contribution to the development of liver abscesses.

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“…The implicated K. pneumoniae strains are generally hypermucoviscous, and their virulence is dependent on the wzyAKpK1 (formerly called magA) gene, which is specific to the K1 serotype (6,7). wzyAKpK1 encodes a polymerase involved in the assembly of the K1 antigen (7,8). Other important virulence factors in these Klebsiella strains include the rmpA gene, which regulates synthesis of the capsule, and aerobactin, a catecholate siderophore (9)(10)(11)(12).…”

mentioning

confidence: 99%

Klebsiella pneumoniae K1 Liver Abscess and Septic Endophthalmitis in a U.S. Resident

et al. 2013

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Klebsiella pneumoniae K1 is a major agent of hepatic abscess with metastatic disease in East Asia, with sporadic reports originating elsewhere. We report a case of abscess complicated by septic endophthalmitis caused by a wzyAKpK1-positive Klebsiella strain in a U.S. resident, raising concern for global emergence. CASE REPORTA 58-year-old female resident of Bronx, New York, who was originally from the Dominican Republic presented with a chief complaint of 1 day of decreased vision in her right eye and concomitant symptoms, including weakness, myalgia, low-grade fever, and right upper quadrant pain for 1 week. She had a history of uncomplicated choledochal cyst resection and Roux-en-Y hepaticojejunostomy approximately 5 years prior to presentation but no history of ocular disease or prior intraocular surgery. She reported subsequent travel to the Dominican Republic but denied travel to Asia at any point before or after her surgery. On the initial ophthalmic examination, visual acuity was 20/60 in the affected eye. Slit-lamp examination revealed moderate conjunctival injection in the right eye, along with 4ϩ cells and hypopyon in the anterior chamber. The fundus view was hazy because of opacity in the anterior segment, but the retina was flat. She was diagnosed with presumed endogenous endophthalmitis. Her vision in the affected eye worsened over the next 24 h. Because of right upper quadrant tenderness on examination, further imaging was performed, revealing a hepatic abscess (7 by 7 by 7 cm) (Fig. 1). The patient reported no history of diabetes, and the serum glucose was normal. She was treated with intravenous levofloxacin, and the abscess was drained percutaneously. Cultures of liver aspirate, blood, and urine grew K. pneumoniae susceptible to expandedand broad-spectrum cephalosporins, ampicillin-sulbactam, levofloxacin, aminoglycosides, and trimethoprim-sulfamethoxazole. The isolate exhibited a hypermucoviscous phenotype, as exemplified by a positive string test (Fig. 2). On the seventh hospital day, her ophthalmologic exam deteriorated; she was found to have a subretinal abscess in the peripheral temporal retina, and retinal detachment was noted (Fig. 3). A sample of vitreous fluid was obtained, which revealed polymorphonuclear leukocytes on Gram stain but a negative culture, and intravitreal injection of ceftazidime was performed. Over the next several weeks, the vitreous debris cleared, and the retina more clearly assumed the configuration of a bullous rhegmatogenous detachment stemming from a break related to the retinal necrosis at the site of the subretinal abscess. The patient underwent a vitrectomy for retinal detachment 2 months after her initial presentation. The patient's subsequent course was complicated by a relapse of abdominal pain and an increase in size of the liver abscess following a transition to oral therapy. An abdominal CT scan conducted 2 months after the completion of an 8-week antibiotic course demonstrated resolution of her liver abscess.Because of the similarity of this case to rep...

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Revisiting the Importance of Virulence DeterminantmagAand Its Surrounding Genes inKlebsiella pneumoniaeCausing Pyogenic Liver Abscesses: Exact Role in Serotype K1 Capsule Formation

Abstract: In accordance with the bacterial polysaccharide gene nomenclature (BPGN) scheme, MagA should be renamed Wzy(KpK1), the capsular polymerase specific to K. pneumoniae serotype K1.

Cited by 81 publications

References 29 publications

Effect in virulence of switching conserved homologous capsular polysaccharide genes fromKlebsiella pneumoniaeserotype K1 into K20

Effect in virulence of switching conserved homologous capsular polysaccharide genes fromKlebsiella pneumoniaeserotype K1 into K20

Immune response and pathophysiological features of Klebsiella pneumoniae liver abscesses in an animal model

Klebsiella pneumoniae K1 Liver Abscess and Septic Endophthalmitis in a U.S. Resident

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