Protective Role of Murine β-Defensins 3 and 4 and Cathelin-Related Antimicrobial Peptide in Fusarium solani Keratitis

Kolar, Satya Sree N.; Baidouri, Hasna; Hanlon, Samuel; McDermott, Alison M.

doi:10.1128/iai.00179-13

Cited by 33 publications

(26 citation statements)

References 38 publications

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“…Previous work identified neutrophil ROS and iron-chelating enzymes as essential in anti-fungal responses during keratitis (7, 8). Furthermore, neutrophils contain numerous anti-microbial peptides and enzymes including defensins, cathelicidin, proteases and chitinases, which potentially mediate killing and degradation of fungal pathogens (34, 35). Therefore CP likely inhibits growth early in infection, which complements other anti-fungal mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Zinc and Manganese Chelation by Neutrophil S100A8/A9 (Calprotectin) Limits Extracellular Aspergillus fumigatus Hyphal Growth and Corneal Infection

Clark

Jhingran

Sun

et al. 2016

The Journal of Immunology

128

110

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Calprotectin, a heterodimer of S100A8 and S100A9, is an abundant neutrophil protein which possesses anti-microbial activity primarily due to its ability to chelate zinc and manganese. In the current study, we showed that neutrophils from calprotectin-deficient S100A9 −/− mice have an impaired ability to inhibit Aspergillus fumigatus hyphal growth in vitro, and in infected corneas in a murine model of fungal keratitis; however, the ability to inhibit hyphal growth was restored in S100A9−/− mice by injecting recombinant calprotectin. Further, using recombinant calprotectin with mutations in either the Zn and Mn binding sites or the Mn binding site alone, we show that both zinc and manganese binding are necessary for calprotectin’s anti-hyphal activity. In contrast to hyphae, we found no role for neutrophil calprotectin in uptake or killing of intracellular A. fumigatus conidia either in vitro, or in a murine model of pulmonary aspergillosis. We also found that an A. fumigatus ΔzafA mutant, which demonstrates deficient zinc transport, exhibits impaired growth in infected corneas and following incubation with neutrophils or calprotectin in vitro as compared to wild-type. Collectively, these studies demonstrate a novel stage - specific susceptibility of A. fumigatus to zinc and manganese chelation by neutrophil-derived calprotectin.

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Section: Discussionmentioning

confidence: 99%

Zinc and Manganese Chelation by Neutrophil S100A8/A9 (Calprotectin) Limits Extracellular Aspergillus fumigatus Hyphal Growth and Corneal Infection

Clark

Jhingran

Sun

et al. 2016

The Journal of Immunology

128

110

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“…AMP is a kind of small molecular polypeptide produced by the natural immune system, which widely exists in plants, insects, and mammals and has a broad-spectrum antimicrobial activity [18,19]. AMPs have an inhibitory effect on multiple species of bacteria, fungus, and even viruses [20][21][22][23][24]. Moreover, AMPs are effective against both planktonic bacteria and bacterial biofilms [25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Effect of a Peptide Containing Novel Oral Spray on Streptococcus mutans

Xiong

Chen

et al. 2020

BioMed Research International

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Objective. To investigate the antibacterial effect of a novel antimicrobial peptide containing oral spray GERM CLEAN on Streptococcus mutans (S. mutans) in vitro and further explore the related mechanisms at phenotypic and transcriptional levels. Methods. The disk diffusion method was used to preliminarily appraise the antimicrobial effect of GERM CLEAN. The minimal inhibitory concentration (MIC) of GREM CLEAN towards S. mutans was determined by the broth dilution method. S. mutans virulence-related phenotypic assays including initial adhesive assay, pH drop, exopolysaccharides (EPS), and biofilm formation measurements and quantitative real-time PCR (qRT-PCR) were further applied to detect the inhibitory mechanisms of GREM CLEAN at 1/2MIC. Results. The diameter (10.18 ± 1.744 mm) of inhibition zones formed by GERM CLEAN preliminarily indicated its inhibitory effect on the major cariogenic bacteria S. mutans. The minimal inhibitory concentration of GERM CLEAN on S. mutans was 100% mass fraction (the stock solution). The study of the antibacterial mechanism showed that GERM CLEAN had a certain inhibitory effect on the initial adhesion, acid production, extracellular polysaccharides (EPS) production, and biofilm formation of S. mutans. GERM CLEAN disturbed S. mutans biofilm physiology mainly through destruction of biofilm architecture and suppression of bacterial growth. The results of qRT-PCR further confirmed that the expression levels of EPS and lactic acid generation genes including gtfB, gtfC, gtfD, and ldh were significantly repressed by treating with GERM CLEAN, and this was consistent with our phenotypic results. Conclusion. The novel antimicrobial peptide containing oral spray GERM CLEAN has an anti-Streptococcus mutans effect and the inhibitory property may be due to suppression of the virulence factors of S. mutans including adhesive, acidogenicity, EPS, and biofilm formation.

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“…Typhimurium) proliferate better within macrophages of mCRAMP knockout mice (39). Cathelicidin-deficient mice are likewise more susceptible to Escherichia coli urinary tract infection (40), meningococcal septicemia (41), Pseudomonas aeruginosa keratitis (42), Klebsiella pneumoniae lung infection (43) and Helicobacter pylori gastritis (23254369), while mice deficient in β-defensin production show impaired defense against P. aeruginosa (44) or Fusarium solani keratitis (45). In gain-of-function analyses, transgenic mice overexpressing porcine cathelicidin were more resistant to bacterial skin infection (46), while transgenic expression of the human defensin-5 in mouse Paneth cells provided enhanced defense against S .…”

Section: Introductionmentioning

confidence: 99%

Bacterial Evasion of Host Antimicrobial Peptide Defenses

Cole

Nizet

2016

Microbiol Spectr

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SUMMARY Antimicrobial peptides (AMPs), also known as host defense peptides, are small naturally occurring microbicidal molecules produced by the host innate immune response that function as a first line of defense to kill pathogenic microorganisms by inducing deleterious cell membrane damage. AMPs also possess signaling and chemoattractant activities and can modulate the innate immune response to enhance protective immunity or suppress inflammation. Human pathogens have evolved defense molecules and strategies to counter and survive the AMPs released by host immune cells such as neutrophils and macrophages. Here, we review the various mechanisms used by human bacterial pathogens to resist AMP-mediated killing, including surface charge modification, active efflux, alteration of membrane fluidity, inactivation by proteolytic digestion, and entrapment by surface proteins and polysaccharides. Enhanced understanding of AMP resistance at the molecular level may offer insight into the mechanisms of bacterial pathogenesis and augment the discovery of novel therapeutic targets and drug design for the treatment of recalcitrant multidrug-resistant bacterial infections.

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Protective Role of Murine β-Defensins 3 and 4 and Cathelin-Related Antimicrobial Peptide in Fusarium solani Keratitis

Cited by 33 publications

References 38 publications

Zinc and Manganese Chelation by Neutrophil S100A8/A9 (Calprotectin) Limits Extracellular Aspergillus fumigatus Hyphal Growth and Corneal Infection

Zinc and Manganese Chelation by Neutrophil S100A8/A9 (Calprotectin) Limits Extracellular Aspergillus fumigatus Hyphal Growth and Corneal Infection

Antimicrobial Effect of a Peptide Containing Novel Oral Spray on Streptococcus mutans

Bacterial Evasion of Host Antimicrobial Peptide Defenses

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