Comparison of the Host Responses to Wild-Type and<i>cpsB</i>Mutant<i>Klebsiella pneumoniae</i>Infections

Lawlor, Matthew S.; Handley, Scott A.; Miller, Virginia L.

doi:10.1128/iai.00244-06

Cited by 70 publications

(74 citation statements)

References 33 publications

(31 reference statements)

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“…It is known that K. pneumoniae strains expressing small amounts of CPS are less virulent than strains expressing larger amounts of CPS (51,52) and, furthermore, that CPS mutants are avirulent in a mouse model of pneumonia (13,41,42). A previous study from our laboratory showed that a CPS mutant is more susceptible to hBD1 than wild-type K. pneumoniae (8), and here we have shown that this is also true for hBD2.…”

Section: Discussionsupporting

confidence: 55%

“…Capsule polysaccharide (CPS) is recognized as one of the most important virulence factors of this pathogen. CPS mutants are unable to colonize pulmonary and systemic tissues (13,41,42). In vitro studies have shown that the presence of CPS inhibits the deposition of the complement component C3 onto the bacterium (5,12,16) and reduces adhesion and phagocytosis of the bacterium by macrophages and epithelial cells (12,13,18,54).…”

mentioning

confidence: 99%

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Klebsiella pneumoniae Capsule Polysaccharide Impedes the Expression of β-Defensins by Airway Epithelial Cells

et al. 2010

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Section: Discussionsupporting

confidence: 55%

mentioning

confidence: 99%

Klebsiella pneumoniae Capsule Polysaccharide Impedes the Expression of β-Defensins by Airway Epithelial Cells

et al. 2010

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“…These cells are part of the innate immune system and Indeed, with bacterial burdens ranging from 10 6 to 10 9 CFU/g tissue in the lungs one would expect a robust proinflammatory response. However, our studies revealed a distinct delay in recruitment of PMNs to the alveolar spaces and lung tissue compared to both our observations of pulmonary infection with other gram-negative pathogens, such as K. pneumoniae, and the observations of other workers (20,21). Importantly, mice from the same shipment as the mice used in the Y. pestis infections that were infected with a lower number of LD 50 s of K. pneumoniae had a strong inflammatory response as early as 24 h postinfection.…”

Section: Discussioncontrasting

confidence: 54%

Delayed Inflammatory Response to Primary Pneumonic Plague Occurs in Both Outbred and Inbred Mice

2007

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Yersinia pestis is the causative agent of plague, a disease that can manifest as either bubonic or pneumonic plague. An interesting feature of plague is that it is a rapidly progressive disease, suggesting that Y. pestis either evades and/or suppresses the innate immune response to infection. Therefore, the early host response during the course of primary pneumonic plague was investigated in two mouse strains, the outbred strain CD1 and the inbred strain C57BL/6. A comparative analysis of the course of disease in these two strains of mice indicated that they are susceptible to intranasal Y. pestis CO92 infection and have similar 50% lethal doses and kinetics of infection with respect to colonization of the lung, liver, and spleen. Significantly, in both strains of mice, robust neutrophil recruitment to the lungs was not observed until 48 h after infection, suggesting that there was a delay in inflammatory cell recruitment to the site of infection. In addition, proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha, gamma interferon, IL-12p70, monocyte chemoattractant protein 1) and chemokines (KC, MIP-2) in the bronchoalveolar lavage fluids were not readily detected until 48 h after infection, which coincided with the increase in polymorphonuclear leukocyte (PMN) recruitment to the lungs. In comparison, CD1 mice with gram-negative pneumonia caused by Klebsiella pneumoniae exhibited strong inflammatory responses early in infection, with PMNs comprising the majority of the cells in the bronchoalveolar lavage fluid 24 h postinfection, indicating that PMN recruitment to the lungs could occur earlier in this infection than in Y. pestis infection. Together, our results indicate that there is a delay in the recruitment of neutrophils to the lungs in the mouse model of primary plague pneumonia that correlates with delayed expression of proinflammatory cytokines and chemokines in both outbred and inbred mice.

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“…2). Acapsular K. pneumoniae strains are dramatically less virulent than isogenic encapsulated strains in mouse models, based on decreased bacterial loads in the lungs, lower rates of mouse mortality, and an inability of the bacteria to spread systemically (167,194,197,198). Furthermore, HV K. pneumoniae strains produce a hypercapsule, also known as being hypermucoviscous, which consists of a mucoviscous exopolysaccharide bacterial coating that is more robust than that of the typical capsule.…”

Section: Capsulementioning

confidence: 99%

“…Capsule, a polysaccharide matrix that coats the cell, is necessary for K. pneumoniae virulence and is arguably the most thoroughly studied virulence factor of K. pneumoniae (79,197) (Fig. 2).…”

Section: Capsulementioning

confidence: 99%

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,293

1,345

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SUMMARYKlebsiella pneumoniaecauses a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically,K. pneumoniaehas caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore,K. pneumoniaestrains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity inK. pneumoniaestrains, and not every factor plays the same critical role in all virulentKlebsiellastrains. Recent studies have identified additionalK. pneumoniaevirulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.

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Comparison of the Host Responses to Wild-Type andcpsBMutantKlebsiella pneumoniaeInfections

Cited by 70 publications

References 33 publications

Klebsiella pneumoniae Capsule Polysaccharide Impedes the Expression of β-Defensins by Airway Epithelial Cells

Klebsiella pneumoniae Capsule Polysaccharide Impedes the Expression of β-Defensins by Airway Epithelial Cells

Delayed Inflammatory Response to Primary Pneumonic Plague Occurs in Both Outbred and Inbred Mice

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

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