Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans.

Studies across various pathogens highlight the importance of pathogen genetic differences in disease manifestation. In the human fungal pathogen Cryptococcus neoformans, sequence type (ST) associates with patient outcome. We performed a meta-analysis of four genomic studies and identified overlapping gene regions associated with virulence, suggesting the importance of these gene regions in cryptococcal disease in diverse clinical isolates.

Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen .

We recently reported transposon mutagenesis as a significant driver of spontaneous mutations in the human fungal pathogen during murine infection. Mutations caused by transposable element (TE) insertion into reporter genes were dramatically elevated at high temperatures (37° vs. 30°) in vitro, suggesting that heat stress stimulates TE mobility in the genome.

Dynamic genome plasticity during unisexual reproduction in the human fungal pathogen Cryptococcus deneoformans.

Genome copy number variation occurs during each mitotic and meiotic cycle and it is crucial for organisms to maintain their natural ploidy. Defects in ploidy transitions can lead to chromosome instability, which is a hallmark of cancer. Ploidy in the haploid human fungal pathogen Cryptococcus neoformans is exquisitely orchestrated and ranges from haploid to polyploid during sexual development and under various environmental and host conditions.

Transposon mobilization in the human fungal pathogen is mutagenic during infection and promotes drug resistance in vitro.

When transitioning from the environment, pathogenic microorganisms must adapt rapidly to survive in hostile host conditions. This is especially true for environmental fungi that cause opportunistic infections in immunocompromised patients since these microbes are not well adapted human pathogens. species are yeastlike fungi that cause lethal infections, especially in HIV-infected patients.

Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi.

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species and , which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models.

Lipooligosaccharide Structure is an Important Determinant in the Resistance of Neisseria Gonorrhoeae to Antimicrobial Agents of Innate Host Defense.

The strict human pathogen Neisseria gonorrhoeae has caused the sexually transmitted infection termed gonorrhea for thousands of years. Over the millennia, the gonococcus has likely evolved mechanisms to evade host defense systems that operate on the genital mucosal surfaces in both males and females. Past research has shown that the presence or modification of certain cell envelope structures can significantly impact levels of gonococcal susceptibility to host-derived antimicrobial compounds that bathe genital mucosal surfaces and participate in innate host defense against invading pathogens.

Regulation of streptokinase expression by CovR/S in Streptococcus pyogenes: CovR acts through a single high-affinity binding site.

The important human pathogen Streptococcus pyogenes (the group A streptococcus or GAS) produces many virulence factors that are regulated by the two-component signal transduction system CovRS (CsrRS). Dissemination of GAS infection originating at the skin has been shown to require production of streptokinase, whose transcription is repressed by CovR. In this work we have studied the interaction of CovR and phosphorylated CovR (CovR-P) with the promoter for streptokinase, Pska.

CovR activation of the dipeptide permease promoter (PdppA) in Group A Streptococcus.

CovR, the two-component response regulator of Streptococcus pyogenes (group A streptococcus [GAS]) directly or indirectly represses about 15% of the genome, including genes encoding many virulence factors and itself. Transcriptome analyses also showed that some genes are activated by CovR. We asked whether the regulation by CovR of one of these genes, dppA, the first gene in an operon encoding a dipeptide permease, is direct or indirect.

Phosphorylation of the group A Streptococcal CovR response regulator causes dimerization and promoter-specific recruitment by RNA polymerase.

The group A streptococcus (GAS), Streptococcus pyogenes, is an important human pathogen that causes infections ranging in severity from self-limiting pharyngitis to severe invasive diseases that are associated with significant morbidity and mortality. The pathogenic effects of GAS are mediated by the expression of virulence factors, one of which is the hyaluronic acid capsule (encoded by genes in the has operon). The expression of these virulence factors is controlled by the CovR/S (CsrR/S) two-component regulatory system of GAS which regulates, directly or indirectly, the expression of about 15% of the genome.

Binding of the global response regulator protein CovR to the sag promoter of Streptococcus pyogenes reveals a new mode of CovR-DNA interaction.

CovR (CsrR) is a response regulator of gene expression in Streptococcus pyogenes. It regulates approximately 15% of the genome, including the genes encoding several streptococcal virulence factors, and acts primarily as a repressor rather than an activator of transcription. We showed that in vitro, CovR is sufficient to repress transcription from the sag promoter, which directs the expression of streptolysin S, a hemolysin that can damage the membranes of eukaryotic cells and subcellular organelles.

The CovR response regulator of group A streptococcus (GAS) acts directly to repress its own promoter.

The CovR/S (CsrR/S) two component system is a global regulator of virulence gene expression in the group A streptococcus (GAS, Streptococcus pyogenes). The response regulator, CovR, regulates about 15% of the genes of GAS, including its own operon. Using in vitro DNA binding assays with purified CovR protein, we found that CovR binds a DNA fragment including the covR promoter (Pcov).

Characterization of the rRNA genes of Ehrlichia chaffeensis and Anaplasma phagocytophila.

The rRNA genes of Ehrlichia chaffeensis and Anaplasma phagocytophila have been analyzed. The 16S rRNA genes were previously characterized for both of these agents. Southern hybridization was used to show that there are single copies of both the 16S and 23S rRNA genes in the genomes of each organism, and that the 16S rRNA genes were upstream from the 23S rRNA genes by at least 16 and 11 Kb for E.

Isolation and characterization of two European strains of Ehrlichia phagocytophila of equine origin.

We report the isolation and partial genetic characterization of two equine strains of granulocytic Ehrlichia of the genogroup Ehrlichia phagocytophila. Frozen whole-blood samples from two Swedish horses with laboratory-verified granulocytic ehrlichiosis were inoculated into HL-60 cell cultures. Granulocytic Ehrlichia was isolated and propagated from both horses.