scholarly journals Genetic Requirements for Klebsiella pneumoniae-Induced Liver Abscess in an Oral Infection Model

2009 ◽  
Vol 77 (7) ◽  
pp. 2657-2671 ◽  
Author(s):  
Ya-Chun Tu ◽  
Min-Chi Lu ◽  
Ming-Ko Chiang ◽  
Shu-Ping Huang ◽  
Hwei-Ling Peng ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Regulatory Networks ◽  
Oral Infection ◽  
Genetic Regulatory Networks ◽  
Class I ◽  
Infection Model ◽  
Wild Type ◽  
Virulence Attenuation ◽  
Mutant Strains

ABSTRACT Klebsiella pneumoniae is the predominant pathogen of primary liver abscess. However, our knowledge regarding the molecular basis of how K. pneumoniae causes primary infection in the liver is limited. We established an oral infection model that recapitulated the characteristics of liver abscess and conducted a genetic screen to identify the K. pneumoniae genes required for the development of liver abscess in mice. Twenty-eight mutants with attenuated growth in liver or spleen samples out of 2,880 signature-tagged mutants that produced the wild-type capsule were identified, and genetic loci which were disrupted in these mutants were identified to encode products with roles in cellular metabolism, adhesion, transportation, gene regulation, and unknown functions. We further evaluated the virulence attenuation of these mutants in independent infection experiments and categorized them accordingly into three classes. In particular, the class I and II mutant strains exhibited significantly reduced virulence in mice, and most of these strains were not detected in extraintestinal tissues at 48 h after oral inoculation. Interestingly, the mutated loci of about one-third of the class I and II mutant strains encode proteins with regulatory functions, and the transcript abundances of many other genes identified in the same screen were markedly changed in these regulatory mutant strains, suggesting a requirement for genetic regulatory networks for translocation of K. pneumoniae across the intestinal barrier. Furthermore, our finding that preimmunization with certain class I mutant strains protected mice against challenge with the wild-type strain implied a potential application for these strains in prophylaxis against K. pneumoniae infections.

scholarly journals Pneumococcal Surface Protein C Contributes to Sepsis Caused by Streptococcus pneumoniae in Mice

2004 ◽  
Vol 72 (5) ◽  
pp. 3077-3080 ◽  
Author(s):  
Francesco Iannelli ◽  
Damiana Chiavolini ◽  
Susanna Ricci ◽  
Marco Rinaldo Oggioni ◽  
Gianni Pozzi
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein C ◽  
Lethal Dose ◽  
Surface Protein ◽  
Infection Model ◽  
Wild Type ◽  
Mutant Strains ◽  
Type 3

ABSTRACT The role of pneumococcal surface protein C (PspC; also called SpsA, CbpA, and Hic) in sepsis by Streptococcus pneumoniae was investigated in a murine infection model. The pspC gene was deleted in strains D39 (type 2) and A66 (type 3), and the mutants were tested by being injected intravenously into mice. The animals infected with the mutant strains showed a significant increase in survival, with the 50% lethal dose up to 250-fold higher than that for the wild type. Our findings indicate that PspC affords a decisive contribution to sepsis development.

scholarly journals Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

2020 ◽  
Author(s):  
Tao Chen ◽  
Guofeng Dong ◽  
Siqin Zhang ◽  
Xiucai Zhang ◽  
Yajie Zhao ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Biofilm Formation ◽  
Iron Chelator ◽  
Infection Model ◽  
Invasive Infection ◽  
Liver Abscesses ◽  
Severe Infections ◽  
Lower Expression ◽  
Additional Iron

Abstract Background: Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. Results: All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P<0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions (P<0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions (P<0.05). Conclusions: It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.

The metallo-sulphur centres of the nitrogenase MoFe protein (Kp1) from wild-type and mutant strains of Klebsiella pneumoniae.

1993 ◽  
Vol 51 (1-2) ◽  
pp. 348
Author(s):  
B.E. Smith ◽  
M. Buck ◽  
K.Y. Faridoon ◽  
C.A. Gormal ◽  
B.D. Howes ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Wild Type ◽  
Mofe Protein ◽  
Mutant Strains

The metallo-sulphur centres of the nitrogenase MoFe protein (Kp1) from wild-type and mutant strains of Klebsiella pneumoniae.

1993 ◽  
Vol 51 (1-2) ◽  
pp. 357
Author(s):  
B.E. Smith ◽  
M. Buck ◽  
K.Y. Faridoon ◽  
C.A. Gormal ◽  
B.D. Howes ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Wild Type ◽  
Mofe Protein ◽  
Mutant Strains

scholarly journals Oral Immunization with an rfaH Mutant Elicits Protection against Salmonellosis in Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 4297-4301 ◽  
Author(s):  
Gábor Nagy ◽  
Ulrich Dobrindt ◽  
Jörg Hacker ◽  
Levente Emödy
Keyword(s):  
Type Strain ◽  
Wild Type Strain ◽  
Lethal Dose ◽  
Fold Increase ◽  
Oral Immunization ◽  
Oral Infection ◽  
Wild Type ◽  
Virulence Attenuation ◽  
Serovar Typhimurium

ABSTRACT Loss of the transcriptional antiterminator RfaH results in virulence attenuation (>104-fold increase in 50% lethal dose) of the archetypal Salmonella enterica serovar Typhimurium strain SL1344 by both orogastric and intraperitoneal routes of infection in BALB/c mice. Oral immunization with the mutant efficiently protects mice against a subsequent oral infection with the wild-type strain. Interestingly, in vitro immunoreactivity is not confined to strain SL1344; rather, it is directed also towards other serovars of S. enterica and even Salmonella bongori strains.

scholarly journals Increased Pho Regulon Activation Correlates with Decreased Virulence of an Avian Pathogenic Escherichia coli O78 Strain

2010 ◽  
Vol 78 (12) ◽  
pp. 5324-5331 ◽  
Author(s):  
Nicolas Bertrand ◽  
Sébastien Houle ◽  
Guillaume LeBihan ◽  
Édith Poirier ◽  
Charles M. Dozois ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Regulatory System ◽  
Rabbit Serum ◽  
Infection Model ◽  
Pho Regulon ◽  
Wild Type ◽  
Mutant Strains ◽  
Pst System

ABSTRACT Avian pathogenic Escherichia coli (APEC) strains are associated with respiratory infections, septicemia, cellulitis, peritonitis, and other conditions, since colibacillosis manifests in many ways. The Pho regulon is jointly controlled by the two-component regulatory system PhoBR and by the phosphate-specific transport (Pst) system. To determine the specific roles of the PhoBR regulon and the Pst system in the pathogenesis of the APEC O78 strain χ7122, different phoBR and pst mutant strains were tested in vivo in chickens and in vitro for virulence traits. Mutations resulting in constitutive activation of the Pho regulon rendered strains more sensitive than the wild type to hydrogen peroxide and to the bactericidal effects of rabbit serum. In addition, production of type 1 fimbriae was also impaired in these strains. Using a chicken competitive infection model, all PhoB constitutive mutants were outcompeted by the wild-type parent, including strains containing a functional Pst system. Cumulative inactivation of the Pst system and the PhoB regulator resulted in a restoration of virulence. In addition, loss of the PhoB regulator alone did not affect virulence in the chicken infection model. Interestingly, the level of attenuation of the mutant strains correlated directly with the level of activation of the Pho regulon. Overall, results indicate that activation of the Pho regulon rather than phosphate transport by the Pst system plays a major role in the attenuation of the APEC O78 strain χ7122.

scholarly journals Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

2020 ◽  
Author(s):  
Tao Chen ◽  
Guofeng Dong ◽  
Siqin Zhang ◽  
Xiucai Zhang ◽  
Yajie Zhao ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Biofilm Formation ◽  
Iron Chelator ◽  
Infection Model ◽  
Invasive Infection ◽  
Liver Abscesses ◽  
Severe Infections ◽  
Lower Expression ◽  
Additional Iron

Abstract Background: Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. Results: All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P<0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions (P<0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions (P<0.05). Conclusions: It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.

scholarly journals A Novel Virulence Gene in Klebsiella pneumoniae Strains Causing Primary Liver Abscess and Septic Metastatic Complications

2004 ◽  
Vol 199 (5) ◽  
pp. 697-705 ◽  
Author(s):  
Chi-Tai Fang ◽  
Yi-Ping Chuang ◽  
Chia-Tung Shun ◽  
Shan-Chwen Chang ◽  
Jin-Town Wang
Keyword(s):  
Infectious Disease ◽  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Virulence Genes ◽  
Wild Type Strain ◽  
Virulence Gene ◽  
Emerging Infectious Disease ◽  
High Serum ◽  
Bacterial Virulence ◽  
Wild Type

Primary Klebsiella pneumoniae liver abscess complicated with metastatic meningitis or endophthalmitis is a globally emerging infectious disease. Its pathogenic mechanism remains unclear. The bacterial virulence factors were explored by comparing clinical isolates. Differences in mucoviscosity were observed between strains that caused primary liver abscess (invasive) and those that did not (noninvasive). Hypermucoviscosity correlated with a high serum resistance and was more prevalent in invasive strains (52/53 vs. 9/52; P &lt; 0.0001). Transposon mutagenesis identified candidate virulence genes. A novel 1.2-kb locus, magA, which encoded a 43-kD outer membrane protein, was significantly more prevalent in invasive strains (52/53 vs. 14/52; P &lt; 0.0001). The wild-type strain produced a mucoviscous exopolysaccharide web, actively proliferated in nonimmune human serum, resisted phagocytosis, and caused liver microabscess and meningitis in mice. However, magA− mutants lost the exopolysaccharide web and became extremely serum sensitive, phagocytosis susceptible, and avirulent to mice. Virulence was restored by complementation using a magA-containing plasmid. We conclude that magA fits molecular Koch's postulates as a virulence gene. Thus, this locus can be used as a marker for the rapid diagnosis and for tracing the source of this emerging infectious disease.

scholarly journals Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

2019 ◽  
Author(s):  
Tao Chen ◽  
Guofeng Dong ◽  
Siqin Zhang ◽  
Xiucai Zhang ◽  
Yajie Zhao ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Biofilm Formation ◽  
Iron Chelator ◽  
Infection Model ◽  
Invasive Infection ◽  
Iron Depletion ◽  
Liver Abscesses ◽  
Severe Infections ◽  
Additional Iron

Abstract Background: Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. Results: All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P<0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron depletion conditions (P<0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron depletion conditions (P<0.05). Conclusions: It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.

scholarly journals Effects of iron on the growth, biofilm formation and virulence of Klebsiella pneumoniae causing liver abscess

2020 ◽  
Author(s):  
Tao Chen ◽  
Guofeng Dong ◽  
Siqin Zhang ◽  
Xiucai Zhang ◽  
Yajie Zhao ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Biofilm Formation ◽  
Iron Chelator ◽  
Infection Model ◽  
Invasive Infection ◽  
Liver Abscesses ◽  
Severe Infections ◽  
Lower Expression ◽  
Additional Iron

Abstract Background: Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. Results: All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator (P<0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions (P<0.05). The relative expression levels of the four siderophore genes (iucB, iroB, irp1, entB) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions (P<0.05). Conclusions: It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses. A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae. Further deeper evaluation of these phenomena is warranted.

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