The Two-Component Sensor Kinase TcsC and Its Role in Stress Resistance of the Human-Pathogenic Mold Aspergillus fumigatus

Mj, Allison; Jacobsen, Ilse D.; Broniszewska, Marzena; Beck, Julia; Heesemann, Jürgen; Ebel, Frank

doi:10.1371/journal.pone.0038262

Cited by 47 publications

(51 citation statements)

References 31 publications

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“…developmental programme responsible for a fluffy, moundshaped morphology (see Fig. 7A and Willger et al, 2009;McCormick et al, 2012). Although no obvious differences in colony morphology were visible between the wild type and the fglA null mutant following longer incubation times in severe hypoxia (0.2%), the fglA mutant showed the tendency to induce a fluffy morphology already at slightly higher O2 concentration than the parental strain (Fig.…”

Section: Fungoglobin Deficiency Promotes Aerial Hyphae Formationmentioning

confidence: 88%

The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus

Hillmann

Linde

Beckmann

et al. 2014

Molecular Microbiology

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SummaryThe human pathogenic fungus Aspergillus fumigatus normally lives as a soil saprophyte. Its environment includes poorly oxygenated substrates that also occur during tissue invasive growth of the fungus in the human host. Up to now, few cellular factors have been identified that allow the fungus to efficiently adapt its energy metabolism to hypoxia. Here, we cultivated A. fumigatus in an O2-controlled fermenter and analysed its responses to O2 limitation on a minute timescale. Transcriptome sequencing revealed several genes displaying a rapid and highly dynamic regulation. One of these genes was analysed in detail and found to encode fungoglobin, a previously uncharacterized member of the sensor globin protein family widely conserved in filamentous fungi. Besides low O2, iron limitation also induced transcription, but regulation was not entirely dependent on the two major transcription factors involved in adaptation to iron starvation and hypoxia, HapX and SrbA respectively. The protein was identified as a functional haemoglobin, as binding of this cofactor was detected for the recombinant protein. Gene deletion in A. fumigatus confirmed that haem-binding fungoglobins are important for growth in microaerobic environments with O 2 levels far lower than in hypoxic human tissue.

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Section: Fungoglobin Deficiency Promotes Aerial Hyphae Formationmentioning

confidence: 88%

The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus

Hillmann

Linde

Beckmann

et al. 2014

Molecular Microbiology

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“…In ascomycetous fungi, hypoxic adaptation extends well beyond balancing sterol biosynthesis covering energy metabolism and a complex developmental program. In A. fumigatus, this program leads to an altered colony morphology and suppresses conidiation during hypoxia (McCormick et al 2012). This program seems to be conserved among other Aspergilli (Fig.…”

Section: Oxygen Levels In the Field Lab And Hostmentioning

confidence: 89%

Insights into the cellular responses to hypoxia in filamentous fungi

2015

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Most eukaryotes require molecular oxygen for growth. In general, oxygen is the terminal electron acceptor of the respiratory chain and represents an important substrate for the biosynthesis of cellular compounds. However, in their natural environment, such as soil, and also during the infection, filamentous fungi are confronted with low levels of atmospheric oxygen. Transcriptome and proteome studies on the hypoxic response of filamentous fungi revealed significant alteration of the gene expression and protein synthesis upon hypoxia. These analyses discovered not only common but also species-specific responses to hypoxia with regard to NAD(+) regeneration systems and other metabolic pathways. A surprising outcome was that the induction of oxidative and nitrosative stress defenses during oxygen limitation represents a general trait of adaptation to hypoxia in many fungi. The interplay of these different stress responses is poorly understood, but recent studies have shown that adaptation to hypoxia contributes to virulence of pathogenic fungi. In this review, results on metabolic changes of filamentous fungi during adaptation to hypoxia are summarized and discussed.

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“…In A. fumigatus , only a few HKs have been characterized so far [18]–[22]. To gain more comprehensive insight into the A. fumigatus TCS, we determined the expression profiles of all HKs.…”

Section: Discussionmentioning

confidence: 99%

NikA/TcsC Histidine Kinase Is Involved in Conidiation, Hyphal Morphology, and Responses to Osmotic Stress and Antifungal Chemicals in Aspergillus fumigatus

et al. 2013

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The fungal high osmolarity glycerol (HOG) pathway is composed of a two-component system (TCS) and Hog1-type mitogen-activated protein kinase (MAPK) cascade. A group III (Nik1-type) histidine kinase plays a major role in the HOG pathway of several filamentous fungi. In this study, we characterized a group III histidine kinase, NikA/TcsC, in the life-threatening pathogenic fungus, Aspergillus fumigatus. A deletion mutant of nikA showed low conidia production, abnormal hyphae, marked sensitivity to high osmolarity stresses, and resistance to cell wall perturbing reagents such as congo red and calcofluor white, as well as to fungicides such as fludioxonil, iprodione, and pyrrolnitrin. None of these phenotypes were observed in mutants of the SskA response regulator and SakA MAPK, which were thought to be downstream components of NikA. In contrast, in response to fludioxonil treatment, NikA was implicated in the phosphorylation of SakA MAPK and the transcriptional upregulation of catA, dprA, and dprB, which are regulated under the control of SakA. We then tested the idea that not only NikA, but also the other 13 histidine kinases play certain roles in the regulation of the HOG pathway. Interestingly, the expression of fos1, phkA, phkB, fhk5, and fhk6 increased by osmotic shock or fludioxonil treatment in a SakA-dependent manner. However, deletion mutants of the histidine kinases showed no significant defects in growth under the tested conditions. Collectively, although the signal transduction network related to NikA seems complicated, NikA plays a crucial role in several aspects of A. fumigatus physiology and, to a certain extent, modulates the HOG pathway.

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The Two-Component Sensor Kinase TcsC and Its Role in Stress Resistance of the Human-Pathogenic Mold Aspergillus fumigatus

Cited by 47 publications

References 31 publications

The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus

The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus

Insights into the cellular responses to hypoxia in filamentous fungi

NikA/TcsC Histidine Kinase Is Involved in Conidiation, Hyphal Morphology, and Responses to Osmotic Stress and Antifungal Chemicals in Aspergillus fumigatus

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