<i>Klebsiella pneumoniae</i>FimK Promotes Virulence in Murine Pneumonia

Rosen, David A.; Hilliard, Julia K.; Tiemann, Kristin M.; Todd, Elizabeth M.; Morley, Sharon Celeste; Hunstad, David A.

doi:10.1093/infdis/jiv440

Cited by 42 publications

(38 citation statements)

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“…K. pneumoniae also carries a gene not carried by E. coli, fimK, whose exact function is unknown. One theory is that FimK is involved in type 1 fimbrial regulation, due to the loss of type 1 fimbria expression upon deletion of fimK (116,283). K. pneumoniae type 1 fimbriae bind D-mannosylated glycoproteins, and therefore, binding by type 1 fimbriae is frequently termed "mannose-sensitive" binding (284,285).…”

Section: Type 1 and 3 Fimbriaementioning

confidence: 99%

“…This suggests that even a small amount of type 1 fimbria expression may be detrimental for survival in these sites. Along these lines, experiments in a mouse model found that a K. pneumoniae strain lacking fimK, which resulted in the overexpression of type 1 fimbriae, was attenuated during lung infection (283). However, it should be noted that this phenotype could also be due to the associated decrease in capsule production that occurs in a fimK mutant (283).…”

Section: Figmentioning

confidence: 99%

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Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,295

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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Section: Type 1 and 3 Fimbriaementioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Paczosa

Mecsas

2016

Microbiol Mol Biol Rev

1,295

1,345

View full text Add to dashboard Cite

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“…Biofilms formation were assayed using the standard crystal violet quantification assay described by O'Toole and associates [88]. Serum-killing assay was performed based on the method described by Rosen and associates [89]. G. mellonella infection assay was conducted as described by McLaughlin and associates [90].…”

Section: Klebsiella Isolated Strainsmentioning

confidence: 99%

Amoxicillin exposure significantly increases the population and virulence of antibiotic-resistant Klebsiella pathogen in the simulated human intestinal microbiota

Liu

Chen

Wang

et al. 2020

Preprint

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Background: The extensive use and misuse of antibiotics have caused the emergence and spread of antibiotic resistance among bacterial pathogens, which is threatening to this idyllic world. The human intestinal microbiota is significant to health, while its composition and stability are easily perturbed by antibiotic exposure. However, the association between antibiotic exposure and the abnormal bloom of opportunistic pathogens in human gut, and its health implications are not fully understood. Therefore, this study investigated the influence of amoxicillin (AMX), one of the most prescribed antibiotics in human life, on human intestinal microbiota using the simulator of the human intestinal microbial ecosystem (SHIME). Results: Our results suggest that AMX exposure could cause the substantial effect on human intestinal microbiota in different colon regions, with most significant alteration in ascending colon. Intriguingly, AMX significantly increased the abundance of antibiotic-resistant Klebsiella pathogen in gut microbiota, resulting in the enrichment of human disease-related pathways. By isolation of Klebsiella strains from SHIME before and after exposure to AMX, we also observed that the virulence phenotypes of these pathogens including biofilm formation, serum resistance, and Galleria mellonella infection were significantly increased after AMX administration. The genotype analysis from whole genome sequencing indicated that the enhanced virulence phenotypes were plausibly caused by the mutations of virulence factors relevant to fimbriae, lipopolysaccharide, capsule, and siderophores. More importantly, the effects from AMX administration could not be fully recovered after two-week drug discontinuance, showing the potential long-term adverse influence of this antibiotic. Conclusions: This study for the first time demonstrates that AMX used for the treatment of bacterial infections may cause adverse effects on human health via significantly increasing population and virulence of intestinal Klebsiella opportunistic pathogen. Given that inherent resistance to β-lactam already poses a significant therapeutic challenge for Klebsiella infections, the AMX-induced virulence increasing phenomenon found in this study undoubtedly further increases its health risk.

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“…MICs of these pathogens were determined according to the CLSI M07-A8 2011 guidelines. The serum-killing assay was performed based on the method described by David and associates [32].…”

Section: Antibiotic Susceptibility Test and Serum Killing Resistance mentioning

confidence: 99%

Human disease-related pathways increasing with opportunistic pathogens bloom in intestinal microbiome after vancomycin exposure and restoration with fecal transplantation by simulator of the human intestinal microbial ecosystem (SHIME)

Liu

Wang

et al. 2019

Preprint

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Background: Antibiotics are growing reported to cause human intestinal microbial disorders with increasing abundances of opportunistic pathogens, and fecal microbiota transplantation (FMT) has been confirmed to restore the dysbiosis of gut flora in many kinds of intestinal disease. However, to date, few studies have focused on the bloomed opportunistic pathogens associated human disease-related pathways as well as antibiotic resistance genes (ARGs) after vancomycin exposure, and there is limited information on using FMT for restoration of intestinal microbiome affected by antibiotics. Methods: This study investigated effects of vancomycin on the opportunistic pathogens, human disease-related pathways as well as ARGs in human gut, and the restoration of intestinal microbiome by FMT. Using the simulator of the human intestinal microbial ecosystem (SHIME), two reactors (representing the ascending and descending colon, respectively) were inoculated with human intestinal microbiota from a healthy adult volunteer who did not suffer from gastrointestinal diseases or take any antibiotic in the previous six months. Samples were collected from the reactors at six-time points (before treatment, after seven days of individual 10 mg/L, 100 mg/L, 1000 mg/L vancomycin treatment, 14 days following the termination of vancomycin and 14 days following FMT). The intestinal microbiome composition and function were analyzed using 16S rRNA gene sequencing and High-throughput Quantitative PCR (HT-qPCR).Results: Vancomycin treatment substantially increased human disease-related pathways and decreased abundances of ARGs. Besides, the bloomed opportunistic pathogens including Achromobacter, Klebsiella, and Pseudomonas, caused by vancomycin exposure, were positively correlated with human disease-related pathways. The microbiota abundance and genes of human disease-related pathways and antibiotic resistance showed a remarkable return towards baseline after FMT, but not for natural recovery. Conclusions: These findings suggest that impacts of vancomycin on human gut are profound and FMT will be a promising strategy in clinical application that can restore the dysbiosis of gut microbiota, which may be valuable for directing future work.

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Klebsiella pneumoniaeFimK Promotes Virulence in Murine Pneumonia

Cited by 42 publications

References 50 publications

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

Amoxicillin exposure significantly increases the population and virulence of antibiotic-resistant Klebsiella pathogen in the simulated human intestinal microbiota

Human disease-related pathways increasing with opportunistic pathogens bloom in intestinal microbiome after vancomycin exposure and restoration with fecal transplantation by simulator of the human intestinal microbial ecosystem (SHIME)

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