Synergistic fight against future pandemics: Lessons from previous pandemics.

The history of pandemics spans centuries and has had a profound impact on human health, societies, and economies. Pandemics have caused fear, panic, and significant morbidity and mortality rates throughout history. From the Athenian Plague in 430 BC to the ongoing COVID-19 pandemic, infectious diseases have posed a continuous threat to global health systems. The transition from hunter-gatherer societies to agrarian communities, increased trade and interaction between humans and animals, urbanization, travel rates, and the impact of a growing human population have all contributed to the emergence and spread of infectious diseases. Climate change and changes in land use further affect the transmission of pathogens and the distribution of disease-carrying vectors. Lessons from previous pandemics include the importance of early diagnosis and response, global cooperation and collaboration, strengthened healthcare systems, preparedness planning, public health education and communication, research and development, and adaptability and flexibility in response strategies. These lessons emphasize the significance of timely identification, swift action, sharing information and resources, investing in healthcare infrastructure, preparedness planning, effective communication, research advancements, and the ability to adapt measures as pandemics evolve. In addition, the COVID-19 pandemic has reinforced the need for a collaborative and coordinated global response to future pandemics. Governments, international bodies, healthcare organizations, and individuals could learn from the lessons of the past and apply them effectively to combat and mitigate the impact of future outbreaks. By prioritizing all the recommendations stated, the world can synergistically protect public health and minimize the devastating consequences of pandemics.

Two hybrid histidine kinases, TcsB and the phytochrome FphA, are involved in temperature sensing in Aspergillus nidulans.

The adaptation of microorganisms to different temperatures is an advantage in habitats with steadily changing conditions and raises the question about temperature sensing. Here we show that in the filamentous fungus Aspergillus nidulans, the hybrid histidine kinase TcsB and phytochrome are involved in temperature-induced gene transcription. Temperature-activated phytochrome fed the signal into the HOG MAP kinase pathway. There is evidence that the photoreceptor phytochrome fulfills a temperature sensory role in plants and bacteria. The effects in plants are based on dark reversion from the active form of phytochrome, Pfr, to the inactive form, Pr. Elevated temperature leads to higher dark reversion rates, and hence, temperature sensing depends on light. In A. nidulans and in Alternaria alternata, the temperature response was light-independent. In order to understand the primary temperature response of phytochrome, we performed spectral analyses of recombinant FphA from both fungi. Spectral properties after heat stress resembled the spectrum of free biliverdin, suggesting conformational changes and a softening of the binding pocket of phytochrome, possibly mimicking photoactivation. We propose a novel function for fungal phytochrome as temperature sensor.

Transcriptomic and Functional Studies of the RGS Protein Rax1 in Aspergillus fumigatus.

In the comparative transcriptomic studies of wild type (WT) and rax1 null mutant strains, we obtained an average of 22,222,727 reads of 101 bp per sample and found that 183 genes showed greater than 2.0-fold differential expression, where 92 and 91 genes were up-and down-regulated in rax1 compared to WT, respectively. In accordance with the significantly reduced levels of gliM and casB transcripts in the absence of rax1, the rax1 mutant exhibited increased sensitivity to exogenous gliotoxin (GT) without affecting levels of GT production. Moreover, rax1 resulted in significantly restricted colony growth and reduced viability under endoplasmic reticulum stress condition. In summary, Rax1 positively affects expression of gliM and metacaspase genes.

Characterization of the rax1 gene encoding a putative regulator of G protein signaling in Aspergillus fumigatus.

The filamentous fungus Aspergillus fumigatus is the major cause of life threatening invasive aspergillosis, and its small hydrophobic asexual spores (conidia) are the major infection agent. To better understand biology of A. fumigatus, we have characterized the rax1 gene encoding a putative regulator of G protein signaling (RGS). The deletion (Δ) of rax1 results in restricted colony growth and highly reduced number of conidia in A. fumigatus. Transcript levels of the three central activators of asexual development abaA, brlA, and wetA are significantly reduced in the Δrax1 mutant. However, the Δrax1 conidia, but not vegetative cells, are specifically resistant against H2O2 stress. The Δrax1 conidia accumulate higher mRNA levels of sakA encoding a key MAP kinase for stress response. Moreover, the Δrax1 conidia contain over five-fold amount of trehalose, an osmolyte and protein/membrane protectant. Transmission electron microscopy analyses indicate that the Δrax1 conidia have the thicker melanized-outermost cell wall layer compared to those of wild-type. In summary, Rax1 positively controls growth and development, and modulates intracellular trehalose amount, cell wall melanin levels in conidia, and spore resistance to H2O2.