Filamentous fungal biofilms: Conserved and unique aspects of extracellular matrix composition, mechanisms of drug resistance and regulatory networks in Aspergillus fumigatus

Liu, Shuai; Mauff, François Le; Sheppard, Donald C.; Zhang, Shizhu

doi:10.1038/s41522-022-00347-3

Cited by 15 publications

(13 citation statements)

References 108 publications

(154 reference statements)

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“…11 In vitro, A. fumigatus was shown to form highly structured biofilms on both biotic and abiotic surfaces. 12 The presence of biofilms has been demonstrated in various Aspergillus diseases such as in people with cystic fibrosis (CF) and those with acute IPA. 13,14 Laboratory studies indicate that the MIC required to kill or inhibit biofilm structures of A. fumigatus are much higher than those required to kill/inhibit planktonic forms.…”

Section: In Vitro Susceptibility Testing and Treatment Failurementioning

confidence: 99%

“…13,14 Laboratory studies indicate that the MIC required to kill or inhibit biofilm structures of A. fumigatus are much higher than those required to kill/inhibit planktonic forms. 12,15 One study indicated that the fungus became increasingly resistant to polyenes, azoles, and echinocandins throughout its morphological differentiation to a mature biofilm phenotype. 12,15 Biofilm formation may reduce the activity of antifungal agents compared to planktonic cells.…”

Section: In Vitro Susceptibility Testing and Treatment Failurementioning

confidence: 99%

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Antifungal Resistance in Pulmonary Aspergillosis

Verweij,

Song,

Buil

et al. 2024

Semin Respir Crit Care Med

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Aspergilli may cause various pulmonary diseases in humans, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and acute invasive pulmonary aspergillosis (IPA). In addition, chronic colonization may occur in cystic fibrosis (CF). Aspergillus fumigatus represents the main pathogen, which may employ different morphotypes, for example, conidia, hyphal growth, and asexual sporulation, in the various Aspergillus diseases. These morphotypes determine the ease by which A. fumigatus can adapt to stress by antifungal drug exposure, usually resulting in one or more resistance mutations. Key factors that enable the emergence of resistance include genetic variation and selection. The ability to create genetic variation depends on the reproduction mode, including, sexual, parasexual, and asexual, and the population size. These reproduction cycles may take place in the host and/or in the environment, usually when specific conditions are present. Environmental resistance is commonly characterized by tandem repeat (TR)-mediated mutations, while in-host resistance selection results in single-resistance mutations. Reported cases from the literature indicate that environmental resistance mutations are almost exclusively present in patients with IA indicating that the risk for in-host resistance selection is very low. In aspergilloma, single-point mutations are the dominant resistance genotype, while in other chronic Aspergillus diseases, for example, ABPA, CPA, and CF, both TR-mediated and single-resistance mutations are reported. Insights into the pathogenesis of resistance selection in various Aspergillus diseases may help to improve diagnostic and therapeutic strategies.

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Section: In Vitro Susceptibility Testing and Treatment Failurementioning

confidence: 99%

Section: In Vitro Susceptibility Testing and Treatment Failurementioning

confidence: 99%

Antifungal Resistance in Pulmonary Aspergillosis

Verweij,

Song,

Buil

et al. 2024

Semin Respir Crit Care Med

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“…GAG is a cationic linear heteropolymer composed of α‐1,4‐linked galactose, N ‐acetylgalactosamine (GalNAc), and galactosamine (GalN) (Fontaine et al, 2011; Speth et al, 2019). As GAG is found on the surface of A. fumigatus hyphae and secreted as component of the extracellular matrix (ECM) of biofilms, it has multiple effects on host immune responses and biofilm formation (Liu et al, 2022; Speth et al, 2019). Interestingly, GAG was found only on the surface of hyphae and was absent in conidia (Briard et al, 2016; Fontaine et al, 2011; Loussert et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Transcription factor CreA is involved in the inverse regulation of biofilm formation and asexual development through distinct pathways in Aspergillus fumigatus

Liu,

Lu,

Dai

et al. 2023

Molecular Microbiology

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The exopolysaccharide galactosaminogalactan (GAG) contributes to biofilm formation and virulence in the pathogenic fungus Aspergillus fumigatus. Increasing evidence indicates that GAG production is inversely linked with asexual development. However, the mechanisms underlying this regulatory relationship are unclear. In this study, we found that the dysfunction of CreA, a conserved transcription factor involved in carbon catabolite repression in many fungal species, causes abnormal asexual development (conidiation) under liquid‐submerged culture conditions specifically in the presence of glucose. The loss of creA decreased GAG production independent of carbon sources. Furthermore, CreA contributed to asexual development and GAG production via distinct pathways. CreA promoted A. fumigatus GAG production by positively regulating GAG biosynthetic genes (uge3 and agd3). CreA suppressed asexual development in glucose liquid‐submerged culture conditions via central conidiation genes (brlA, abaA, and wetA) and their upstream activators (flbC and flbD). Restoration of brlA expression to the wild‐type level by flbC or flbD deletion abolished the abnormal submerged conidiation in the creA null mutant but did not restore GAG production. The C‐terminal region of CreA was crucial for the suppression of asexual development, and the repressive domain contributed to GAG production. Overall, CreA is involved in GAG production and asexual development in an inverse manner.

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“…Subsequently it was confirmed that filamentous fungi such as A. fumigatus , Aspergillus spp., F. graminearum , F. solani , F. oxysporum , Fusarium spp., Botrytis spp., and Verticillium spp. [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] form biofilms. Despite these studies, mixed polymicrobial biofilms of a filamentous fungus and a bacterium on the ocular surface have been rarely studied.…”

Section: Introductionmentioning

confidence: 99%

Differential Susceptibility of Mixed Polymicrobial Biofilms Involving Ocular Coccoid Bacteria (Staphylococcus aureus and S. epidermidis) and a Filamentous Fungus (Fusarium solani) on Ex Vivo Human Corneas

2023

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Biofilms confer several advantages to the organisms associated with them, such as increased resistances to antibacterial and antifungal compounds compared to free living cells. Compared to monomicrobial biofilms involving a single microorganism, biofilms composed of microorganisms affiliated to bacterial and fungal kingdoms are predominant in nature. Despite the predominance of polymicrobial biofilms, and more so mixed polymicrobial biofilms, they are rarely studied. The objective of the current study is to evaluate the potential of ocular bacteria and a filamentous fungus to form monomicrobial and mixed polymicrobial biofilms on synthetic and natural substrates and to monitor their response to antibiotics. In this sense, we demonstrated that the ocular pathogens Staphylococcus aureus, S. epidermidis, and Fusarium solani form monomicrobial and mixed polymicrobial biofilms both on tissue culture polystyrene plates and on ex vivo human corneas from cadavers using confocal microscopy and scanning electron microscopy. Additionally, the mixed polymicrobial biofilms involving the above ocular bacteria and a filamentous fungus were less susceptible to different antibacterials and antifungals in relation to the corresponding control planktonic cells. Further, the MICs to the screened antibacterials and antifungals in polymicrobial biofilms involving a bacterium or a fungus was either increased, decreased, or unchanged compared to the corresponding individual bacterial or fungal biofilm. The results would be useful to the ophthalmologist to plan effective treatment regimens for the eye since these are common pathogens of the eye causing keratitis, endophthalmitis, conjunctivitis, etc.

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Filamentous fungal biofilms: Conserved and unique aspects of extracellular matrix composition, mechanisms of drug resistance and regulatory networks in Aspergillus fumigatus

Cited by 15 publications

References 108 publications

Antifungal Resistance in Pulmonary Aspergillosis

Antifungal Resistance in Pulmonary Aspergillosis

Transcription factor CreA is involved in the inverse regulation of biofilm formation and asexual development through distinct pathways in Aspergillus fumigatus

Differential Susceptibility of Mixed Polymicrobial Biofilms Involving Ocular Coccoid Bacteria (Staphylococcus aureus and S. epidermidis) and a Filamentous Fungus (Fusarium solani) on Ex Vivo Human Corneas

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