CYP1B1-AS1 regulates CYP1B1 to promote pathogenesis by inhibiting ROS and host cell death.

(Cb), the causative agent of Q fever, replicates within host macrophages by modulating immune responses through poorly understood mechanisms. Long non-coding RNAs (lncRNAs) are emerging as critical regulators of inflammation, yet their role in Cb pathogenesis remains largely unexplored. Here, we employed a global transcriptomic approach to identify lncRNAs specific to Cb infection in THP-1 derived macrophages, compared to 15 other microbial infections.

The emerging roles of long non-coding RNA in host immune response and intracellular bacterial infections.

The long non-coding RNAs (lncRNAs) are evolutionarily conserved classes of non-coding regulatory transcripts of > 200 nucleotides in length. They modulate several transcriptional and post-transcriptional events in the organism. Depending on their cellular localization and interactions, they regulate chromatin function and assembly; and alter the stability and translation of cytoplasmic mRNAs.

Primary Murine Macrophages as a Tool for Virulence Factor Discovery in Coxiella burnetii.

Coxiella burnetii requires a type IVB secretion system (T4SS) to promote intracellular replication and virulence. We hypothesized that employs its T4SS to secrete effectors that enable stealthy colonization of immune cells. To address this, we used RNA sequencing to compare the transcriptional response of murine bone marrow-derived macrophages (BMDM) infected with those of wild-type and a T4SS-null mutant at 8 and 24 h postinfection.

Immunogenicity and Reactogenicity in Q Fever Vaccine Development.

is an obligate intracellular bacterium which, in humans, causes the disease Q fever. Although Q fever is most often a mild, self-limiting respiratory disease, it can cause a range of severe syndromes including hepatitis, myocarditis, spontaneous abortion, chronic valvular endocarditis, and Q fever fatigue syndrome. This agent is endemic worldwide, except for New Zealand and Antarctica, transmitted aerosols, persists in the environment for long periods, and is maintained through persistent infections in domestic livestock.

Soluble antigens derived from elicit protective immunity in three animal models without inducing hypersensitivity.

Q fever is caused by the intracellular bacterium , for which there is no approved vaccine in the United States. A formalin-inactivated whole-cell vaccine (WCV) from virulent NMI provides single-dose long-lived protection, but concerns remain over vaccine reactogenicity. We therefore sought an alternate approach by purifying native antigens from the clonally derived avirulent NMII strain.

inhibits host immunity by a protein phosphatase adapted from glycolysis.

is a bacterial pathogen that replicates within host cells by establishing a membrane-bound niche called the -containing vacuole. Biogenesis of this compartment requires effectors of its Dot/Icm type IV secretion system. A large cohort of such effectors has been identified, but the function of most of them remain elusive.

Whole Cell Vaccine Produces a Th1 Delayed-Type Hypersensitivity Response in a Novel Sensitized Mouse Model.

Q-VAX®, a whole cell, formalin-inactivated vaccine, is the only vaccine licensed for human use to protect against , the cause of Q fever. Although this vaccine provides long-term protection, local and systemic reactogenic responses are common in previously sensitized individuals which prevents its use outside of Australia. Despite the importance of preventing these adverse reactions to develop widely accepted, novel vaccines against , little is understood about the underlying cellular mechanisms.

Automated, High-Throughput Detection of Bacterial Adherence to Host Cells.

Identification of emerging bacterial pathogens is critical for human health and security. Bacterial adherence to host cells is an essential step in bacterial infections and constitutes a hallmark of potential threat. Therefore, examining the adherence of bacteria to host cells can be used as a component of bacterial threat assessment.

Subunit Vaccines Using TLR Triagonist Combination Adjuvants Provide Protection Against While Minimizing Reactogenic Responses.

Q fever is caused by the obligate intracellular bacterium, , a designated potential agent of bioterrorism because of its route of transmission, resistance to disinfectants, and low infectious dose. The only vaccine licensed for human use is Q-VAX (Seqirus, licensed in Australia), a formalin-inactivated whole-cell vaccine, which produces severe local and systemic reactogenic responses in previously sensitized individuals. Accordingly, the U.

Intratracheal Inoculation with Brucella melitensis in the Pregnant Guinea Pig Is an Improved Model for Reproductive Pathogenesis and Vaccine Studies.

Reproductive failure is the hallmark of brucellosis in animals. An uncommon but important complication in pregnant women who become acutely infected with is spontaneous pregnancy loss or vertical transmission to the fetus. Unfortunately, the mechanism behind reproductive failure is still obscure, partially due to the lack of a proper study model.

Chemokine Receptor 7 Is Essential for Coxiella burnetii Whole-Cell Vaccine-Induced Cellular Immunity but Dispensable for Vaccine-Mediated Protective Immunity.

Background: Protective immunity against Coxiella burnetii infection is conferred by vaccination with virulent (PI-WCV), but not avirulent (PII-WCV) whole-cell inactivated bacterium. The only well-characterized antigenic difference between virulent and avirulent C. burnetii is they have smooth and rough lipopolysaccharide (LPS), respectively.

Quantitative Yeast Genetic Interaction Profiling of Bacterial Effector Proteins Uncovers a Role for the Human Retromer in Salmonella Infection.

Intracellular bacterial pathogens secrete a repertoire of effector proteins into host cells that are required to hijack cellular pathways and cause disease. Despite decades of research, the molecular functions of most bacterial effectors remain unclear. To address this gap, we generated quantitative genetic interaction profiles between 36 validated and putative effectors from three evolutionarily divergent human bacterial pathogens and 4,190 yeast deletion strains.

Identification and characterization of arginine finger-like motifs, and endosome-lysosome basolateral sorting signals within the Coxiella burnetii type IV secreted effector protein CirA.

Coxiella burnetii is an obligate intracellular pathogen that replicates in an endolysosome-like compartment termed the Coxiella-containing vacuole (CCV). Formation of this unique replicative niche requires delivery of bacterial effector proteins into the host cytosol where they mediate crucial interactions with the host. We previously identified an essential Dot/Icm effector, CirA that is required for intracellular replication and CCV formation.

Use of Reverse Vaccinology in the Design and Construction of Nanoglycoconjugate Vaccines against Burkholderia pseudomallei.

is a Gram-negative, facultative intracellular pathogen that causes the disease melioidosis in humans and other mammals. Respiratory infection with leads to a fulminant and often fatal disease. It has previously been shown that glycoconjugate vaccines can provide significant protection against lethal challenge; however, the limited number of known antigens has slowed progress toward vaccine development.

Global Reprogramming of Host Kinase Signaling in Response to Fungal Infection.

Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular lifestyle is important for virulence. Host mechanisms controlling fungal phagocytosis and replication remain obscure. Here, we perform a global phosphoproteomic analysis of the host response to Cryptococcus infection.

The SCID Mouse Model for Identifying Virulence Determinants in .

is an intracellular, zoonotic pathogen that is the causative agent of Q fever. Infection most frequently occurs after inhalation of contaminated aerosols, which can lead to acute, self-limiting febrile illness or more serve chronic infections such as hepatitis or endocarditis. Macrophages are the principal target cells during infection where resides and replicates within a unique phagolysosome-like compartment, the -containing vacuole (CCV).

Identification of Coxiella burnetii CD8+ T-Cell Epitopes and Delivery by Attenuated Listeria monocytogenes as a Vaccine Vector in a C57BL/6 Mouse Model.

Coxiella burnetii is a gram-negative bacterium that causes acute and chronic Q fever. Because of the severe adverse effect of whole-cell vaccination, identification of immunodominant antigens of C. burnetii has become a major focus of Q fever vaccine development.

The Type IV Secretion System Effector Protein CirA Stimulates the GTPase Activity of RhoA and Is Required for Virulence in a Mouse Model of Coxiella burnetii Infection.

Coxiella burnetii, the etiological agent of Q fever in humans, is an intracellular pathogen that replicates in an acidified parasitophorous vacuole derived from host lysosomes. Generation of this replicative compartment requires effectors delivered into the host cell by the Dot/Icm type IVb secretion system. Several effectors crucial for C.

Contrasting Lifestyles Within the Host Cell.

Intracellular bacterial pathogens have evolved to exploit the protected niche provided within the boundaries of a eukaryotic host cell. Upon entering a host cell, some bacteria can evade the adaptive immune response of its host and replicate in a relatively nutrient-rich environment devoid of competition from other host flora. Growth within a host cell is not without their hazards, however.

Space: A Final Frontier for Vacuolar Pathogens.

There is a fundamental gap in our understanding of how a eukaryotic cell apportions the limited space within its cell membrane. Upon infection, a cell competes with intracellular pathogens for control of this same precious resource. The struggle between pathogen and host provides us with an opportunity to uncover the mechanisms regulating subcellular space by understanding how pathogens modulate vesicular traffic and membrane fusion events to create a specialized compartment for replication.

Modulation of the host transcriptome by Coxiella burnetii nuclear effector Cbu1314.

Coxiella burnetii is a Gram-negative, obligate intracellular pathogen that directs the formation of a parasitophorous vacuole derived from the host lysosomal network. Biogenesis and maintenance of this replicative compartment is dependent on bacterial protein synthesis and results in differential expression of specific host genes. However, the mechanisms by which the pathogen induces changes in the host transcriptome is poorly understood.

Surfactant Protein D Binds to Coxiella burnetii and Results in a Decrease in Interactions with Murine Alveolar Macrophages.

Coxiella burnetii is a Gram-negative, obligate intracellular bacterium and the causative agent of Q fever. Infections are usually acquired after inhalation of contaminated particles, where C. burnetii infects its cellular target cells, alveolar macrophages.

Cloning, expression, and characterization of a Coxiella burnetii Cu/Zn Superoxide dismutase.

Background: Periplasmically localized copper-zinc co-factored superoxide dismutase (SodC) enzymes have been identified in a wide range of Gram-negative bacteria and are proposed to protect bacteria from exogenously produced toxic oxygen radicals, which indicates the potential significance of a Coxiella burnetii SodC.

Results: Assays for SOD activity demonstrated that the cloned C. burnetii insert codes for a SOD that was active over a wide range of pH and inhibitable with 5 mM H2O2 and 1 mM sodium diethyldithiocarbamate, a characteristic of Cu/ZnSODs that distinguishes them from Fe or Mn SODs.