Susceptibilities of<i>Cryptococcus neoformans</i>Strains to Platelet Binding In Vivo and to the Fungicidal Activity of Thrombin-Induced Platelet Microbicidal Proteins In Vitro

Nail, Sandrine; Robert, Raymond; Dromer, Françoise; Marot-Leblond, A.; Senet, Jean-Marcel

doi:10.1128/iai.69.2.1221-1225.2001

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…These observations further support our hypotheses (7,8,50) that (i) the antimicrobial effects of tPMP-1 are likely most important in limiting the proliferation phase of infection, rather than initial adhesion of pathogens to a target tissue, (ii) a tPMP-1 s phenotype in vitro translates to reduced achievable microbial densities in vivo in specific target tissues compared to the tPMP-1 r phenotype, and (iii) the tPMP-1 r phenotype likely confers survival advantages to pathogens in selected target tissues. Similarly, Nail et al have recently demonstrated that tPMPs likely influence clearance of fungi from the bloodstream in a murine model of infection (31). Together, these data support the idea that platelet release of PMPs in vivo contributes an important host defense role against Candida.…”

supporting

confidence: 72%

Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Increased Fluconazole Efficacy against Experimental Endocarditis Due to Candida albicans

Yeaman

Cheng²,

Desai³

et al. 2004

Antimicrob Agents Chemother

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Platelet microbicidal proteins (PMPs) are believed to be integral to host defense against endovascular infection. We previously demonstrated that susceptibility to thrombin-induced PMP 1 (tPMP-1) in vitro negatively influences Candida albicans virulence in the rabbit model of infective endocarditis (IE). This study evaluated the relationship between in vitro tPMP-1 susceptibility (tPMP-1 s ) or resistance (tPMP-1 r ) and efficacy of fluconazole (FLU) therapy of IE due to C. albicans. Candida IE was established in rabbits with either tPMP-1 s or tPMP-1 r strains. Treatment groups received FLU (100 mg/kg/day) intraperitoneally for 7 or 14 days; control animals received no therapy. At these time points, cardiac vegetations, kidneys, and spleens were quantitatively cultured to assess fungal burden. At both 7 and 14 days and in all target tissues, the extent of candidal clearance by FLU was greater in animals infected with the tPMP-1 s strain than in those infected with the tPMP-1 r strain. These differences were statistically significant in the spleen and kidney. Corroborating these in vivo data, FLU (a candidastatic agent), in combination with tPMP-1, exerted an enhanced fungicidal effect in vitro against tPMP-1 s and tPMP-1 r C. albicans, with the extent of this effect greatest against the tPMP-1 s strain. Collectively, these results support the concept that tPMP-1 susceptibility contributes to the net efficacy of FLU against C. albicans IE in vivo, particularly in tissues in which platelets and tPMP-1 likely play significant roles in host defense.

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supporting

confidence: 72%

Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Increased Fluconazole Efficacy against Experimental Endocarditis Due to Candida albicans

Yeaman

Cheng²,

Desai³

et al. 2004

Antimicrob Agents Chemother

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“…More detailed analyses revealed differences in the platelet interaction between capsular and non-encapsulated cryptococcal strains. Platelets exclusively attached to non-encapsulated isolates, which were also the only ones to be susceptible to antifungal activity of the platelet microbicidal peptide tPMP (63). Further platelet-derived proteins that act fungicidal against Cryptococcus are thrombocidins, RANTES, PF-4 and the fibrinopeptins (9,59).…”

Section: Cryptococcusmentioning

confidence: 99%

Platelet immunology in fungal infections

Speth¹,

Rambach²,

Lass‐Flörl³

2014

Thromb Haemost

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Up to date, perception of platelets has changed from key players in coagulation to multitaskers within the immune network, connecting its most diverse elements and crucially shaping their interplay with invading pathogens such as fungi. In addition, antimicrobial effector molecules and mechanisms in platelets enable a direct inhibitory effect on fungi, thus completing their immune capacity. To precisely assess the impact of platelets on the course of invasive fungal infections is complicated by some critical parameters. First, there is a fragile balance between protective antimicrobial effects and detrimental reactions that aggravate the fungal pathogenesis. Second, some platelet effects are exerted indirectly by other immune mediators and are thus difficult to quantify. Third, drugs such as antimycotics, antibiotics, or cytostatics, are commonly administered to the patients and might modulate the interplay between platelets and fungi. Our article highlights selected aspects of the complex interactions between platelets and fungi and the relevance of these processes for the pathogenesis of fungal infections.

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“…Platelets liberate platelet microbicidal proteins (PMPs) when activated, thereby contributing to the host defence against infection. PMPs from thrombin-induced rabbit, and human platelets, also called the kinocidins (hPF-4), were isolated and characterized and were shown to have potent microbicidal activity against pathogens of the bloodstream, such as Staphylococcus aureus, Streptococcus viridans, Escherichia coli, Candida albicans and Cryptococcus neoformans [10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Enhanced antimicrobial activity of peptide-cocktails against common bacterial contaminants of ex vivo stored platelets

Mohan

Rao

Gao

et al. 2014

Clinical Microbiology and Infection

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Bacterial contamination of blood components such as ex vivo-stored platelets is a major safety risk in transfusion medicine. We have recently shown that synthetic antimicrobial peptides named PD1-PD4 derived from the thrombin-induced human platelet-derived antimicrobial proteins, and repeats of Arg-Trp (RW1-RW5) demonstrate microbicidal activity against selected bacteria and viruses. In the present study, we selected PD3, PD4, RW2, RW3 and RW4 and evaluated each individual peptide and their various combinations to see whether the cocktail regimen enhances the antimicrobial activity above and over the individual peptides. Stored platelet or plasma samples spiked with known titres of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Bacillus cereus were treated with either individual peptides or with peptides in various combinations. Analyses revealed that individual peptides show moderate microbicidal activity (10- to 100-fold reduction) against the tested bacteria relative to their combined regimen. The peptide combinations (RW2 + RW4, RW2 + RW3 + RW4 and PD4 + RW3 + RW4) on the other hand enhanced the microbicidal activity (c.10 000-fold reduction) and revealed a minimal inhibitory concentration of 5 μM. Time-kill kinetics indicated that these three peptide combinations exhibited enhanced antimicrobial activity bringing about a 100-fold reduction of bacterial titres within 20 min of incubation. The present study therefore demonstrates the synergistic effect of antimicrobial peptides when used in combinations and provides a proof-of-concept of its potential application as a molecular tool towards pathogen reduction and further extends the possibility of using peptide combinatorial therapeutics as broad-spectrum antibiotics or as alternatives to combat drug-resistant bacteria.

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Susceptibilities ofCryptococcus neoformansStrains to Platelet Binding In Vivo and to the Fungicidal Activity of Thrombin-Induced Platelet Microbicidal Proteins In Vitro

Cited by 6 publications

References 33 publications

Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Increased Fluconazole Efficacy against Experimental Endocarditis Due to Candida albicans

Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Increased Fluconazole Efficacy against Experimental Endocarditis Due to Candida albicans

Platelet immunology in fungal infections

Enhanced antimicrobial activity of peptide-cocktails against common bacterial contaminants of ex vivo stored platelets

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