Project description:Opportunistic infections of the respiratory tract often succeed under a weakened immune response caused by an underlying illness or hospitalization. The human fungal pathogen, Cryptococcus neoformans, and the bacterial pathogen, Klebsiella pneumoniae, are both well-characterized microbes that cause severe infections within immunocompromised individuals. In this study, we simulate a concentration-dependent pulmonary coinfection of a bacterial and fungal pathogen, and profile the proteomic changes by DDA vs. DIA. Dual perspective profiling provides new insights into host defense regulation of infection and pathogenic mechanisms of invasion.
Project description:Streptococcus pyogenes (Group A Streptococcus: GAS) is a major human pathogen that causes streptococcal pharyngitis, skin and soft-tissue infections, and life-threatening conditions such as streptococcal toxic shock syndrome (STSS). A large number of virulence-related genes are encoded on GAS genomes, which are involved in host-pathogen interaction, colonization, immune invasion, and long-term survival within hosts, causing the diverse symptoms. Here, we investigated the interaction between GAS-derived extracellular vesicles and host cells in order to reveal pathogenicity mechanisms induced by GAS infection.
Project description:Trichophyton rubrum, an anthropophilic and cosmopolitan fungus, is the most common agent of superficial mycoses, causing rarely deep dermatophytosis in immunocompromised hosts. In this study, an infection condition of T. rubrum was modeled by adding human skin sections into a limited medium containing glucose to monitor T. rubrum gene expression patterns using cDNA microarrays on a global level. We found that exposure to human skin resulted in up-regulation of the expression levels of T. rubrum genes related to many cellular and biological processes, including transcription and translation, metabolism and secondary transport, stress response, and signaling pathways. These results provide a reference set of T. rubrum genes whose expression patterns change upon infection and reveal previously unknown genes that probably corresponding to proteins that should be considered as virulence factor candidates and potential new drug targets for T. rubrum infections.
Project description:Ticks are blood feeding arthropod ectoparasites that transmit pathogens, which cause diseases in humans and animals worldwide. In the past ten decades, the continuous human exploitation of environmental resources and the increase in human outdoor activities has promoted contact with arthropod vectors normally present in the wild, resulting in increased transmission of vector-borne pathogens. In addition, vector populations are expanding in response to climate change and human interventions that impact reservoir host movement and human exposure to infected vectors. Among these emerging vector-borne pathogens, Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) has become an important tick-borne pathogen in the United States, Europe and Asia, with increasing numbers of infected people and animals every year. Diseases caused by A. phagocytophilum include human granulocytic anaplasmosis (HGA), equine and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. The natural infection cycle of A. phagocytophilum is dependent upon the presence of infected vertebrate reservoir hosts and Ixodid tick vectors. In the United States and Europe the main vector species are Ixodes scapularis, Ixodes pacificus, and Ixodes ricinus, while a wide range of mammals, lizards, and birds serve as reservoir hosts for various A. phagocytophilum genotypes. A. phagocytophilum initially infects tick midgut cells and then subsequently develops in salivary glands for transmission to susceptible hosts during tick feeding where the pathogen infects granulocytic cells, primarily neutrophils. Anaplasma phagocytophilum develops within membrane-bound inclusions in the host cell cytoplasm. This pathogen has evolved with its tick and vertebrate hosts through dynamic processes involving genetic traits of the pathogen and hosts that collectively mediate pathogen infection, development, persistence, and survival. However, the mechanisms used by A. phagocytophilum for molecular mechanisms involved in tick-pathogen interactions have not been fully characterized. The objective of this study is to characterize the dynamics of the microRNA response in the tick vector Ixodes scapularis in response to A. phagocytophilum infection. To address this objective, the composition of tick microRNAs was characterize using RNA sequencing in I. scapularis tick cells in response to A. phagocytophilum infection. The discovery of these mechanisms provides evidence that a control strategy could be developed targeted at both vertebrate and tick hosts for more complete control of A. phagocytophilum and its associated diseases.
Project description:Escherichia coli is the most widely studied strains, which has irreplaceable position in medicine and biology research. Pseudomonas aeruginosa, an opportunistic human pathogen, tends to cause potentially lethal acute or chronic infections in patients with cystic fibrosis (CF), immunocompromised individuals and burn victims. However, it is little know about the effect of the special secondary structure rG4 (G-quadruplex) in the mRNA on virulence regulation. Here, we aim to reveal the new and important post-transcriptional regulatory roles of rG4 in bacterial pathogenicity and metabolic pathways.
Project description:Pseudomonas aeruginosa is an opportunistic human pathogen, infecting immuno-compromised patients and causing persistent respiratory infections in people affected from cystic fibrosis. Pseudomonas strain Pseudomonas aeruginosa PA14 shows higher virulence than Pseudomonas aeruginosa PAO1 in a wide range of hosts including insects, nematodes and plants but the precise cause of this difference is not fully understood. Little is known about the host response upon infection with Pseudomonas and whether or not transcription is being affected as a host defense mechanism or altered in the benefit of the pathogen. In this context the social amoeba Dictyostelium discoideum has been described as a suitable host to study virulence of Pseudomonas and other opportunistic pathogens.
Project description:Trichophyton rubrum, an anthropophilic and cosmopolitan fungus, is the most common agent of superficial mycoses, causing rarely deep dermatophytosis in immunocompromised hosts.
Project description:Candida albicans is the most important fungal pathogen of humans, causing severe infections especially in nosocomial and immunocompromised settings. However, it is also the most prevalent fungus of the normal human microbiome, where it shares its habitat with hundreds of trillions of other microbial cells. Despite weak organic acids (WOAs) being among the most abundant metabolites produced by bacterial microbiota, little is known about their effect on C. albicans. Here we employed a sequencing-based profiling strategy to systematically investigate the transcriptional stress response of C. albicans to lactic, acetic, propionic and butyric acid at several time points after treatment. Our data reveal a complex transcriptional response, with individual WOAs triggering unique gene expression profiles and with important differences between acute and chronic exposure. In spite of all these dissimilarities, we found significant overlaps between the gene expression changes induced by each WOA, which lead us to uncover a core transcriptional signature that was unrelated to the general response to low pH. Genes commonly up-regulated by WOAs were enriched in several iron transporters, which was associated with an overall decrease in intracellular iron concentrations. Moreover, chronic exposure to any WOA lead to down-regulation of RNA synthesis and ribosome biogenesis genes, which resulted in significant reduction of total RNA levels in general and of ribosomal RNA in particular. In conclusion, this study suggests that GI microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its hosts in both health and disease. Transcriptional profiling of wild-type Candida albicans strain SC5314 under 6 differents condition (2 controls, 4 weak acids) at 4 time points by cDNA deep-sequencing, with 4 biological replicates, on the Illumina HiSeq 2000 platform. 96 total samples were sequenced (6 x 4 x 4).