Candida Worsens Klebsiella pneumoniae Induced-Sepsis in a Mouse Model with Low Dose Dextran Sulfate Solution through Gut Dysbiosis and Enhanced Inflammation

Abstract

Klebsiella pneumoniae is an opportunistic pathogen and a commensal organism that is possibly enhanced in several conditions with gut dysbiosis, and frequently detectable together with Candida overgrowth. Here, K. pneumoniae with or without Candida albicans was daily orally administered for 3 months in 0.8% dextran sulfate solution-induced mucositis mice and also tested in vitro. As such, Candida worsened Klebsiella-DSS-colitis as demonstrated by mortality, leaky gut (FITC-dextran assay, bacteremia, endotoxemia, and serum beta-glucan), gut dysbiosis (increased Deferribacteres from fecal microbiome analysis), liver pathology (histopathology), liver apoptosis (activated caspase 3), and cytokines (in serum and in the internal organs) when compared with Klebsiella-administered DSS mice. The combination of heat-killed Candida plus Klebsiella mildly facilitated inflammation in enterocytes (Caco-2), hepatocytes (HepG2), and THP-1-derived macrophages as indicated by supernatant cytokines or the gene expression. The addition of heat-killed Candida into Klebsiella preparations upregulated TLR-2, reduced Occludin (an intestinal tight junction molecule), and worsened enterocyte integrity (transepithelial electrical resistance) in Caco-2 and enhanced casp8 and casp9 (apoptosis genes) in HepG2 when compared with heat-killed Klebsiella alone. In conclusion, Candida enhanced enterocyte inflammation (partly through TLR-2 upregulation and gut dysbiosis) that induced gut translocation of endotoxin and beta-glucan causing hyper-inflammatory responses, especially in hepatocytes and macrophages.

Rapid Synergistic Biofilm Production of Pseudomonas and Candida on the Pulmonary Cell Surface and in Mice, a Possible Cause of Chronic Mixed Organismal Lung Lesions

“…Due to the biofilm production of C. albicans being less than that of P. aeruginosa [ 9 ], the pulmonary cells (NCI-H292) with biofilms from P. aeruginosa plus C. albicans or P. aeruginosa alone were used for a proteomic analysis. Notably, the initial abundance of P. aeruginosa in the Pseudomonas alone (PA) group was approximately 2-fold higher than that in the Pseudomonas plus Candida (PA+CA) group due to the protocol to ensure a similar total organismal abundance between both conditions (PA vs. PA+CA).…”

“…Likewise, 20% of systemic Candida albicans infections are polymicrobial, with Staphylococcus epidermidis and Staphylococcus aureus being the first and third most common co-isolated organisms, respectively, with a strong interspecies biofilm formation [ 7 , 8 ]. Moreover, an enhanced severity of infection with the co-presence of C. albicans and Klebsiella pneumoniae has been reported [ 9 ]. However, Pseudomonas aeruginosa and Candida albicans are two of the most common opportunistic pathogens that usually colonize numerous sites of the human body, resulting in several diseases, including burn wounds, contaminated catheters, and infections in several organs (the genitourinary tract, gut, and lung).…”

Gut Barrier Damage and Gut Translocation of Pathogen Molecules in Lupus, an Impact of Innate Immunity (Macrophages and Neutrophils) in Autoimmune Disease

“…Notably, gut dysbiosis can be a cause or a consequence of gut leakage. As such, oral administration of bacteria or fungi caused leaky gut from an increase in pathobionts [ 62 , 63 ], while leaky gut by dextran sulfate induces dysbiosis [ 26 ]. Gut dysbiosis in SLE might be a result of a combination of (i) the genetic defects in the immune responses against some gut organisms that selectively allow some group of organisms to survive in the gut, together with (ii) the gut environmental factors from the host behaviors (diets, alcohol, smoking, and medications).…”

Candida Administration in 5/6 Nephrectomized Mice Enhanced Fibrosis in Internal Organs: An Impact of Lipopolysaccharide and (1→3)-β-D-Glucan from Leaky Gut

“…Although the presence of Candida spp. in the gut does not directly cause disease, gut fungi alter the gut microbiota and provide a higher BG in gut content [13], which possibly worsens systemic inflammation following a gut barrier malfunction (gut leakage) through the systemic immune responses against BG [14][15][16][17][18][19][20]. Indeed, the possible fungal mechanisms that interfere with the growth of specific bacteria (mostly the lower virulence) in the gut are mentioned, including some bactericidal molecules (yeast killer toxins, Candida exotoxin, and endogenous alcohol) [21][22][23][24], and the competition for certain nutrients [25].…”