Establishment of Experimental Murine Peritonitis Model with Hog Gastric Mucin for Carbapenem-Resistant Gram-Negative Bacteria

Park, Jung Yeon; Park, Chulmin; Chun, Hye Sun; Byun, Ji Hyun; Cho, Sung‐Yeon; Lee, Dong Gun

doi:10.3947/ic.2017.49.1.57

Cited by 8 publications

(11 citation statements)

References 17 publications

(14 reference statements)

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“…Female BALB/c mice were infected systemically with a lethal dose of NDM-HK in the presence of 2% mucin. Mucin is the macromolecular component of mammalian mucus, and commixture of mucin is used to enhance the bacterial pathogenicity in mouse peritoneal cavity 28 , 45 , whereas mice showed no morbidity or mortality when mucin was used alone. The infected mice were then administrated with a vehicle control, MER or CBS monotherapy or combination therapy, 4 h post infection, followed by twice-daily treatment via i.p.…”

Section: Resultsmentioning

confidence: 99%

Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors

et al. 2018

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Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.

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Section: Resultsmentioning

confidence: 99%

Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors

et al. 2018

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“…infection with A. baumannii strains of different virulence. Several laboratories have used porcine mucin to enhance the virulence of various A. baumannii clinical and type strains in mice (13,21,(24)(25)(26)(27). In this study, we assessed the relative virulence of 3 A. baumannii strains (ATCC 19606 T , ATCC 17961, and LAC-4) by the inclusion of mucin in the inocula.…”

Section: Resultsmentioning

confidence: 99%

“…1D), suggesting that the mucin-enhanced virulence in A. baumannii is not restricted to BALB/c mice. In this regard, other mouse strains, such as ICR-Swiss, Swiss White, and CF-1, previously have been used in similar models (16,18,19,26), although actual magnitudes of the enhancement in some of those studies had not been reported in detail.…”

Section: Resultsmentioning

confidence: 99%

Potential Mechanisms of Mucin-Enhanced Acinetobacter baumannii Virulence in the Mouse Model of Intraperitoneal Infection

et al. 2019

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Porcine mucin has been commonly used to enhance the infectivity of bacterial pathogens, including Acinetobacter baumannii, in animal models, but the mechanisms for enhancement by mucin remain relatively unknown. In this study, using the mouse model of intraperitoneal (i.p.) mucin-enhanced A. baumannii infection, we characterized the kinetics of bacterial replication and dissemination and the host innate immune responses, as well as their potential contribution to mucin-enhanced bacterial virulence. We found that mucin, either admixed with or separately injected with the challenge bacterial inoculum, was able to enhance the tissue and blood burdens of A. baumannii strains of different virulence. Intraperitoneal injection of A. baumannii-mucin or mucin alone induced a significant but comparable reduction of peritoneal macrophages and lymphocytes, accompanied by a significant neutrophil recruitment and early interleukin-10 (IL-10) responses, suggesting that the resulting inflammatory cellular and cytokine responses were largely induced by the mucin. Depletion of peritoneal macrophages or neutralization of endogenous IL-10 activities showed no effect on the mucin-enhanced infectivity. However, pretreatment of mucin with iron chelator DIBI, but not deferoxamine, partially abolished its virulence enhancement ability, and replacement of mucin with iron significantly enhanced the bacterial burdens in the peritoneal cavity and lung. Taken together, our results favor the hypothesis that iron at least partially contributes to the mucin-enhanced infectivity of A. baumannii in this model.

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“…Many reports have suggested that bacteria can exploit mucin secreted by the human mucosa to survive and escape host defence systems . It is well known that a lethal dose of various bacteria in animal experimental models can be reduced when mucin is added to bacteria .…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that a lethal dose of various bacteria in animal experimental models can be reduced when mucin is added to bacteria . It has also been shown that a 3% mucin solution from porcine stomach was enough to increase the virulence of E. coli , Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii in a mouse peritonitis model . Salmonella enterica serovar Typhi enhanced its virulence in a murine model of infection .…”

Section: Discussionmentioning

confidence: 99%

Mucin adsorbed by E. coli can affect neutrophil activation in vitro

et al. 2019

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Bacteria colonizing human intestine adhere to the gut mucosa and avoid the innate immune system. We previously demonstrated that Escherichia coli isolates can adsorb mucin from a diluted solution in vitro. Here, we evaluated the effect of mucin adsorption by E. coli cells on neutrophil activation in vitro. Activation was evaluated based on the detection of reactive oxygen species production by a chemiluminescent reaction (ChL), observation of morphological alterations in neutrophils and detection of exocytosis of myeloperoxidase and lactoferrin. We report that mucin adsorbed by cells of SharL1 isolate from Crohn's disease patient's inflamed ileum suppressed the potential for the activation of neutrophils in whole blood. Also, the binding of plasma complement proteins and immunoglobulins to the bacteria was reduced. Desialylated mucin, despite having the same adsorption efficiency to bacteria, had no effect on the blood ChL response. The effect of mucin suggests that it shields epitopes that interact with neutrophils and plasma proteins on the bacterial outer membrane. Potential candidates for these epitopes were identified among the proteins within the bacterial outer membrane fraction by 2D‐PAGE, fluorescent mucin binding on a blot and HPLC‐MS/MS. In vitro, the following proteins demonstrated mucin adsorption: outer membrane porins (OmpA, OmpC, OmpD and OmpF), adhesin OmpX, the membrane assembly factor OmpW, cobalamine transporter, ferrum uptake protein and the elongation factor Ef Tu‐1. In addition to their other functions, these proteins are known to be bacterial surface antigens. Therefore, the shielding of epitopes by mucin may affect the dynamics and intensity of an immune response.

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Establishment of Experimental Murine Peritonitis Model with Hog Gastric Mucin for Carbapenem-Resistant Gram-Negative Bacteria

Cited by 8 publications

References 17 publications

Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors

Bismuth antimicrobial drugs serve as broad-spectrum metallo-β-lactamase inhibitors

Potential Mechanisms of Mucin-Enhanced Acinetobacter baumannii Virulence in the Mouse Model of Intraperitoneal Infection

Mucin adsorbed by E. coli can affect neutrophil activation in vitro

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