scholarly journals Tools for Assessing Translation in Cryptococcus neoformans

2021 ◽  
Vol 7 (3) ◽  
pp. 159
Author(s):  
Corey M. Knowles ◽  
Kelcy M. McIntyre ◽  
John C. Panepinto

Cryptococcus neoformans is a ubiquitous environmental fungus capable of establishing an infection in a human host. Rapid changes in environments and exposure to the host immune system results in a significant amount of cellular stress, which is effectively combated at the level of translatome reprogramming. Repression of translation following stress allows for the specific reallocation of limited resources. Understanding the mechanisms involved in regulating translation in C. neoformans during host infection is critical in the development of new antifungal drugs. In this review, we discuss the main tools available for assessing changes in translation state and translational output during cellular stress.

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Serena Delbue ◽  
Manola Comar ◽  
Pasquale Ferrante

The polyomaviruses are small DNA viruses that can establish latency in the human host. The name polyomavirus is derived from the Greek rootspoly-, which means “many,” and -oma, which means “tumours.” These viruses were originally isolated in mouse (mPyV) and in monkey (SV40). In 1971, the first human polyomaviruses BK and JC were isolated and subsequently demonstrated to be ubiquitous in the human population. To date, at least nine members of thePolyomaviridaefamily have been identified, some of them playing an etiological role in malignancies in immunosuppressed patients. Here, we describe the biology of human polyomaviruses, their nonmalignant and malignant potentials ability, and their relationship with the host immune response.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 314 ◽  
Author(s):  
Jakub Suchodolski ◽  
Daria Derkacz ◽  
Jakub Muraszko ◽  
Jarosław J. Panek ◽  
Aneta Jezierska ◽  
...  

Recognizing the β-glucan component of the Candida albicans cell wall is a necessary step involved in host immune system recognition. Compounds that result in exposed β-glucan recognizable to the immune system could be valuable antifungal drugs. Antifungal development is especially important because fungi are becoming increasingly drug resistant. This study demonstrates that lipopeptide, surfactin, unmasks β-glucan when the C. albicans cells lack ergosterol. This observation also holds when ergosterol is depleted by fluconazole. Surfactin does not enhance the effects of local chitin accumulation in the presence of fluconazole. Expression of the CHS3 gene, encoding a gene product resulting in 80% of cellular chitin, is downregulated. C. albicans exposure to fluconazole changes the composition and structure of the fungal plasma membrane. At the same time, the fungal cell wall is altered and remodeled in a way that makes the fungi susceptible to surfactin. In silico studies show that surfactin can form a complex with β-glucan. Surfactin forms a less stable complex with chitin, which in combination with lowering chitin synthesis, could be a second anti-fungal mechanism of action of this lipopeptide.


2021 ◽  
Vol 7 (2) ◽  
pp. 133
Author(s):  
Rayssa Karla de Medeiros Oliveira ◽  
Fabián Andrés Hurtado ◽  
Pedro Henrique Gomes ◽  
Luiza Lassi Puglia ◽  
Fernanda Fonsêca Ferreira ◽  
...  

Pathogenic microbes are exposed to a number of potential DNA-damaging stimuli during interaction with the host immune system. Microbial survival in this situation depends on a fine balance between the maintenance of DNA integrity and the adaptability provided by mutations. In this study, we investigated the association of the DNA repair response with the virulence of Cryptococcus neoformans, a basidiomycete that causes life-threatening meningoencephalitis in immunocompromised individuals. We focused on the characterization of C. neoformansAPN1 and APN2 putative genes, aiming to evaluate a possible role of the predicted Apurinic/apyrimidinic (AP) endonucleases 1 and 2 of the base excision repair (BER) pathway on C. neoformans response to stress conditions and virulence. Our results demonstrated the involvement of the putative AP-endonucleases Apn1 and Apn2 in the cellular response to DNA damage induced by alkylation and by UV radiation, in melanin production, in tolerance to drugs and in virulence of C. neoformans in vivo. We also pointed out the potential use of DNA repair inhibitor methoxy-amine in combination with conventional antifungal drugs, for the development of new therapeutic approaches against this human fungal pathogen. This work provides new information about the DNA damage response of the highly important pathogenic fungus C. neoformans.


2021 ◽  
Vol 11 ◽  
Author(s):  
Chalita Chomkatekaew ◽  
Phumrapee Boonklang ◽  
Apiwat Sangphukieo ◽  
Claire Chewapreecha

A better understanding of co-evolution between pathogens and hosts holds promise for better prevention and control strategies. This review will explore the interactions between Burkholderia pseudomallei, an environmental and opportunistic pathogen, and the human host immune system. B. pseudomallei causes “Melioidosis,” a rapidly fatal tropical infectious disease predicted to affect 165,000 cases annually worldwide, of which 89,000 are fatal. Genetic heterogeneities were reported in both B. pseudomallei and human host population, some of which may, at least in part, contribute to inter-individual differences in disease susceptibility. Here, we review (i) a multi-host—pathogen characteristic of the interaction; (ii) selection pressures acting on B. pseudomallei and human genomes with the former being driven by bacterial adaptation across ranges of ecological niches while the latter are driven by human encounter of broad ranges of pathogens; (iii) the mechanisms that generate genetic diversity in bacterial and host population particularly in sequences encoding proteins functioning in host—pathogen interaction; (iv) reported genetic and structural variations of proteins or molecules observed in B. pseudomallei—human host interactions and their implications in infection outcomes. Together, these predict bacterial and host evolutionary trajectory which continues to generate genetic diversity in bacterium and operates host immune selection at the molecular level.


mBio ◽  
2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Teresa R. O'Meara ◽  
Stephanie M. Holmer ◽  
Kyla Selvig ◽  
Fred Dietrich ◽  
J. Andrew Alspaugh

ABSTRACTInfectious microorganisms often play a role in modulating the immune responses of their infected hosts. We demonstrate thatCryptococcus neoformanssignals through the Rim101 transcription factor to regulate cell wall composition and the host-pathogen interface. In the absence of Rim101,C. neoformansexhibits an altered cell surface in response to host signals, generating an excessive and ineffective immune response that results in accelerated host death. This host immune response to therim101Δ mutant strain is characterized by increased neutrophil influx into the infected lungs and an altered pattern of host cytokine expression compared to the response to wild-type cryptococcal infection. To identify genes associated with the observed phenotypes, we performed whole-genome RNA sequencing experiments under capsule-inducing conditions. We defined the downstream regulon of the Rim101 transcription factor and determined potential cell wall processes involved in the capsule attachment defects and altered mechanisms of virulence in therim101Δ mutant. The cell wall generates structural stability for the cell and allows the attachment of surface molecules such as capsule polysaccharides. In turn, the capsule provides an effective mask for the immunogenic cell wall, shielding it from recognition by the host immune system.IMPORTANCECryptococcus neoformansis an opportunistic human pathogen that is a significant cause of death in immunocompromised individuals. There are two major causes of death due to this pathogen: meningitis due to uncontrolled fungal proliferation in the brain in the face of a weakened immune system and immune reconstitution inflammatory syndrome characterized by an overactive immune response to subclinical levels of the pathogen. In this study, we examined howC. neoformansuses the conserved Rim101 transcription factor to specifically remodel the host-pathogen interface, thus regulating the host immune response. These studies explored the complex ways in which successful microbial pathogens induce phenotypes that ensure their own survival while simultaneously controlling the nature and degree of the associated host response.


2021 ◽  
Author(s):  
Nedaa Alomari ◽  
Farizeh Aalasm ◽  
Romina Nabiee ◽  
Jesus Ramirez Castano ◽  
Jennifer Totonchy

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) extensively manipulates the host immune system and the cytokine milieu, and cytokines are known to influence the progression of KSHV-associated diseases. However, the precise role of cytokines in the early stages of KSHV infection remains undefined. Here, using our unique model of KSHV infection in tonsil lymphocytes, we investigate the influence of host cytokines on the establishment of KSHV infection in B cells. Our data demonstrate that KSHV manipulates the host cytokine microenvironment during early infection and susceptibility generally associated with downregulation of multiple cytokines. However, we show that IL-21 signaling promotes KSHV infection by promoting both plasma cell numbers and increasing KSHV infection in plasma cells. Our data reveal that IL-21 producing T cells, particularly Th17/Tc17 and central memory CD8+ T cells may represent immunological factors that modulate host-level susceptibility to KSHV infection. These results suggest that IL-21 plays a significant role in the early stages of KSHV infection in the human immune system and may represent a novel mechanism to be further explored in the context of preventing KSHV transmission.Author SummaryVery little is known about how KSHV is transmitted and how it initially establishes infection in a new human host and this lack of information limits our ability to prevent KSHV-associated cancers by limiting its person-to-person transmission. Saliva is thought to be the primary route of person-to-person transmission for KSHV, making the tonsil a likely first site for KSHV replication in a new human host. In particular, the tonsil is likely to be the first place KSHV is able to enter B cells, which are thought to be a major site of persistent infection. Our previous work identified plasma cells as a highly targeted cell type in early KSHV infection in cultured cells from human tonsil. In this study, we show that the human cytokine IL-21 promotes both overall KSHV infection and the establishment of infection in plasma cells. We also investigate the immunological mechanisms underlying this effect. Our results demonstrate that IL-21 and IL-21-producing cells are a novel factor that influences the initial establishment of KSHV infection in humans.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 259-261
Author(s):  
Aamir Khan ◽  
Rajni K. Gurmule

Vasavaleha is one of the best medicine given for respiratory diseases. Corona viruses typically affect the respiratory system, causing symptoms such as coughing, fever and shortness of breath. It also affects host immune system of human body. Spreading rate of this disease is very high. Whole world is seeking for the treatment which can uproots this diseases. There in no vaccine available till date against this pandemic disease. Ayurveda mainly focuses on prevention of diseases alongwith its total cure. Rajyakshma Vyadhi is MadhyamMarga Roga as per Ayurveda. It shows many symptoms such as Kasa, Shwasa etc. By overall view of Covid 19, shows its resemblance with Rajyakshma Vyadhi described in Ayurveda. Vasavaleha is a Kalpa which is described in Rogadhikara of Rajyakshma. It shows Kasahara, Shwashara properties. It consists of Vasa, Pipalli, Madhu and Goghrita. These components shows actions like bronchodilation, antitussive effect and many more other actions. Pipalli shows important Rasayana effect. So in present review, we have tried to focus on role of Vasavaleha in the management of Covid 19. This can be used as preventive as well as adjuvant medication in treating Covid 19. There is need of further clinical research to rule of exact action of Vasavaleha against Covid 19.


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