Characteristics, Clinical Relevance, and the Role of Echinocandins in Fungal–Bacterial Interactions

Arvanitis, Marios; Mylonakis, Eleftherios

doi:10.1093/cid/civ816

Cited by 9 publications

(9 citation statements)

References 43 publications

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“…Biofilm formation is not only relevant on teeth, but also on medical devices such as implants or catheters and in wounds [114,115]. Biofilms are medically relevant because they serve as infection reservoirs for microbes [114,116,117]. Antimicrobial effectors, such as host immune cells or antibiotics, are less potent towards biofilm-associated bacteria and fungi as compared with planktonic microbes [118].…”

Section: Fungal-bacterial Interactions—niche By Nichementioning

confidence: 99%

Fungal-Bacterial Interactions in Health and Disease

et al. 2019

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Fungi and bacteria encounter each other in various niches of the human body. There, they interact directly with one another or indirectly via the host response. In both cases, interactions can affect host health and disease. In the present review, we summarized current knowledge on fungal-bacterial interactions during their commensal and pathogenic lifestyle. We focus on distinct mucosal niches: the oral cavity, lung, gut, and vagina. In addition, we describe interactions during bloodstream and wound infections and the possible consequences for the human host.

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Section: Fungal-bacterial Interactions—niche By Nichementioning

confidence: 99%

Fungal-Bacterial Interactions in Health and Disease

et al. 2019

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“…Furthermore, our study in a fungal mono-infection model cannot recapitulate the complexity of trauma-related soft tissue infections that are often polymicrobial in nature (1, 9–15). Cross-kingdom interactions of pathogens have been increasingly recognized as key virulence determinants shaping the outcomes of life-threatening infectious diseases (54–55). Direct physical interaction, inter-kingdom signaling, altered immunopathology, and competition for nutrients or trace elements are considered to play a driving role in the mutual modulation of bacterial and fungal virulence (54, 56).…”

Section: Discussionmentioning

confidence: 99%

“…Cross-kingdom interactions of pathogens have been increasingly recognized as key virulence determinants shaping the outcomes of life-threatening infectious diseases (54–55). Direct physical interaction, inter-kingdom signaling, altered immunopathology, and competition for nutrients or trace elements are considered to play a driving role in the mutual modulation of bacterial and fungal virulence (54, 56). Interestingly, preliminary results of R. arrhizus and Staphylococcus aureus co-infection studies in our fruit fly model suggest that TSC-induced hyper-virulence rather increases in a mixed infection setting (Wurster et al, unpublished data), highlighting a need to obtain a more refined understanding of the influence of shear forces on the complex inter-dependencies in polymicrobial infections.…”

Section: Discussionmentioning

confidence: 99%

Tornadic shear stress induces a transient, calcineurin-dependent hyper-virulent phenotype in Mucorales molds

Wurster

Tatara

Albert

et al. 2020

Preprint

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6Trauma-related necrotizing myocutaneous mucormycosis (NMM) has a high morbidity and mortality in 2 7 victims of combat-related injuries, geo-meteorological disasters, and severe burns. Inspired by the obser-2 8 vation that several recent clusters of NMM have been associated with extreme mechanical forces (e.g. 2 9during tornados), we studied the impact of mechanical stress on Mucoralean biology and virulence in a 3 0 Drosophila melanogaster infection model. In contrast to other experimental procedures to exert mechani-3 1 cal stress, tornadic shear challenge (TSC) by magnetic stirring induced a hyper-virulent phenotype in sev-3 2 eral clinically relevant Mucorales species but not in Aspergillus or Fusarium. Whereas fungal growth 3 3 rates, morphogenesis, and susceptibility to noxious environments or phagocytes were not altered by TSC, 3 4 soluble factors released in the supernatant of shear-challenged R. arrhizus spores rendered static spores 3 5 hyper-virulent. Consistent with a rapid decay of TSC-induced hyper-virulence, minimal transcriptional 3 6 changes were revealed by comparative RNA sequencing analysis of static and shear-challenged Rhizopus 3 7 arrhizus. However, inhibition of the calcineurin/heat shock protein 90 (hsp90) stress response circuitry by 3 8 cyclosporine A (CsA) and tanespimycin abrogated the increased pathogenicity of R. arrhizus spores fol-3 9 lowing TSC. Similarly, calcineurin loss-of-function mutants of Mucor circinelloides displayed no in-4 0 creased virulence capacity in flies after undergoing TSC. Collectively, these results establish that TSC 4 1 induces hyper-virulence specifically in Mucorales and point out the calcineurin/hsp90 pathway as a key 4 2 orchestrator of this phenotype. Our findings invite future studies of topical calcineurin inhibitor treatment 4 3 of wounds as an adjunct mitigation strategy for NMM following high-energy trauma. 4 4 3 Significance 4 5 Given the limited efficacy of current medical treatments in trauma-related necrotizing mucormycosis, 4 6there is a dire need to better understand the Mucoralean pathophysiology in order to develop novel strate-4 7 gies to counteract fungal tissue invasion following severe trauma. Here, we describe that tornadic shear 4 8 stress challenge transiently induces a hyper-virulent phenotype in various pathogenic Mucorales species 4 9

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“…In 1974 the first member of another group of antifungals also active against fungal biofilms was found [107,108]. This group of cyclopetides esterified with a long-chain fatty acid is named echinocandins after its first representative echinocandin B 78, from Aspergillus echinulatus [109,110].…”

Section: From Papulacandins and Echinocandins To Drugs Against Fungalmentioning

confidence: 99%

Fungal Metabolites for the Control of Biofilm Infections

Estrela

Abraham

2016

Agriculture

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Many microbes attach to surfaces and produce a complex matrix of polymers surrounding their cells, forming a biofilm. In biofilms, microbes are much better protected against hostile environments, impairing the action of most antibiotics. A pressing demand exists for novel therapeutic strategies against biofilm infections, which are a grave health wise on mucosal surfaces and medical devices. From fungi, a large number of secondary metabolites with antimicrobial activity have been characterized. This review discusses natural compounds from fungi which are effective against fungal and bacterial biofilms. Some molecules are able to block the cell communication process essential for biofilm formation (known as quorum sensing), others can penetrate and kill cells within the structure. Several targets have been identified, ranging from the inhibition of quorum sensing receptors and virulence factors, to cell wall synthesizing enzymes. Only one group of these fungal metabolites has been optimized and made it to the market, but more preclinical studies are ongoing to expand the biofilm-fighting arsenal. The broad diversity of bioactive compounds from fungi, their activities against various pathogens, and the multi-target trait of some molecules are promising aspects of fungal secondary metabolites. Future screenings for biofilm-controlling compounds will contribute to several novel clinical applications.

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Characteristics, Clinical Relevance, and the Role of Echinocandins in Fungal–Bacterial Interactions

Cited by 9 publications

References 43 publications

Fungal-Bacterial Interactions in Health and Disease

Fungal-Bacterial Interactions in Health and Disease

Tornadic shear stress induces a transient, calcineurin-dependent hyper-virulent phenotype in Mucorales molds

Fungal Metabolites for the Control of Biofilm Infections

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