An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms.

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens.

Autophagy facilitates intracellular survival of pathogenic rickettsiae in macrophages via evasion of autophagosomal maturation and reduction of microbicidal pro-inflammatory IL-1 cytokine responses.

spp. are intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some rickettsiae are responsible for several severe human diseases globally.

Pathogenic, but Not Nonpathogenic, spp. Evade Inflammasome-Dependent IL-1 Responses To Establish an Intracytosolic Replication Niche.

species (spp.) are strict obligate intracellular bacteria, some of which are pathogenic in their mammalian host, including humans. One critical feature of these stealthy group of pathogens is their ability to manipulate hostile cytosolic environments to their benefits.

Anti-inflammatory activity of crude and detoxified leaves of Daphne oleoides Schreb. on carrageenan-induced paw edema in wistar rats.

Background: Mazaryun (Daphne oleoides Schreb.) is used as an anti-inflammatory drug in Unani medicine after detoxification, as it is defined under fourth-degree drugs.

Objective(s): To evaluate and compare the anti-inflammatory activity of crude and detoxified Mazaryun in maximum and minimum doses.

Lipid A Structural Divergence in Pathogens.

Species of (: ) are obligate intracellular parasites of a wide range of eukaryotes, with recognized arthropod-borne human pathogens belonging to the transitional group (TRG), typhus group (TG), and spotted fever group (SFG) rickettsiae. Growing in the host cytosol, rickettsiae pilfer numerous metabolites to make a typical Gram-negative bacterial cell envelope. The O-antigen of rickettsial lipopolysaccharide (LPS) is immunogenic and has been shown to tether the S-layer to the rickettsial surface; however, little is known about the structure and immunogenicity of the lipid A moiety.

Rickettsia-host interaction: strategies of intracytosolic host colonization.

Bacterial infection is a highly complex biological process involving a dynamic interaction between the invading microorganism and the host. Specifically, intracellular pathogens seize control over the host cellular processes including membrane dynamics, actin cytoskeleton, phosphoinositide metabolism, intracellular trafficking and immune defense mechanisms to promote their host colonization. To accomplish such challenging tasks, virulent bacteria deploy unique species-specific secreted effectors to evade and/or subvert cellular defense surveillance mechanisms to establish a replication niche.

A chromosome-level assembly of the cat flea genome uncovers rampant gene duplication and genome size plasticity.

Background: Fleas (Insecta: Siphonaptera) are small flightless parasites of birds and mammals; their blood-feeding can transmit many serious pathogens (i.e., the etiological agents of bubonic plague, endemic and murine typhus).

Risk1, a Phosphatidylinositol 3-Kinase Effector, Promotes Rickettsia typhi Intracellular Survival.

To establish a habitable intracellular niche, various pathogenic bacteria secrete effectors that target intracellular trafficking and modulate phosphoinositide (PI) metabolism. Murine typhus, caused by the obligate intracellular bacterium , remains a severe disease in humans. However, the mechanisms by which effector molecules contribute to internalization by induced phagocytosis and subsequent phagosomal escape into the cytosol to facilitate the intracellular growth of the bacteria remain ill-defined.

Scientific appraisal of Unani concept of islah-e-advia (rectification/purification of drugs) and its importance.

Ethnopharmacological Relevance: Unani system of medicine uses drugs from plants, minerals and animals (Mawaleed-e-salasa) origin. Most of the drugs used are believed to be safe, but some drugs may have toxins and produce harmful effects, so it is very important to remove the toxins or to minimize their harmful effects before using, so as to increase their therapeutic values and make easy for use.

Aim Of The Study: To explore the concept, aims and objectives of islah-e-advia (rectification/purification of drugs) in Unani system of medicine.

Rickettsia Lipid A Biosynthesis Utilizes the Late Acyltransferase LpxJ for Secondary Fatty Acid Addition.

Members of the genus are obligate intracellular, Gram-negative coccobacilli that infect mammalian and arthropod hosts. Several rickettsial species are human pathogens and are transmitted by blood-feeding arthropods. In Gram-negative parasites, the outer membrane (OM) sits at the nexus of the host-pathogen interaction and is rich in lipopolysaccharide (LPS).

The Rickettsial Ankyrin Repeat Protein 2 Is a Type IV Secreted Effector That Associates with the Endoplasmic Reticulum.

Strains of , the tick-borne agent of Rocky Mountain spotted fever, vary considerably in virulence. Genomic comparisons of strains have identified a relatively small number of genes divergent in an avirulent strain. Among these is one annotated as ankyrin repeat protein 2 (RARP-2).

The Cat Flea (Ctenocephalides felis) Immune Deficiency Signaling Pathway Regulates Rickettsia typhi Infection.

species are obligate intracellular bacteria with both conserved and lineage-specific strategies for invading and surviving within eukaryotic cells. One variable component of biology involves arthropod vectors: for instance, typhus group rickettsiae are principally vectored by insects (i.e.

Wholly ! Reconstructed Metabolic Profile of the Quintessential Bacterial Parasite of Eukaryotic Cells.

Reductive genome evolution has purged many metabolic pathways from obligate intracellular (; ). While some aspects of host-dependent rickettsial metabolism have been characterized, the array of host-acquired metabolites and their cognate transporters remains unknown. This dearth of information has thwarted efforts to obtain an axenic culture, a major impediment to conventional genetic approaches.

RalF-Mediated Activation of Arf6 Controls Rickettsia typhi Invasion by Co-Opting Phosphoinositol Metabolism.

Rickettsiae are obligate intracellular pathogens that induce their uptake into nonphagocytic cells; however, the events instigating this process are incompletely understood. Importantly, diverse Rickettsia species are predicted to utilize divergent mechanisms to colonize host cells, as nearly all adhesins and effectors involved in host cell entry are differentially encoded in diverse Rickettsia species. One particular effector, RalF, a Sec7 domain-containing protein that functions as a guanine nucleotide exchange factor of ADP-ribosylation factors (Arfs), is critical for Rickettsia typhi (typhus group rickettsiae) entry but pseudogenized or absent from spotted fever group rickettsiae.

Structural Insight into How Bacteria Prevent Interference between Multiple Divergent Type IV Secretion Systems.

Unlabelled: Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.

Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion.

Bacterial Sec7-domain-containing proteins (RalF) are known only from species of Legionella and Rickettsia, which have facultative and obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS) effector, is a guanine nucleotide exchange factor (GEF) of ADP-ribosylation factors (Arfs), activating and recruiting host Arf1 to the Legionella-containing vacuole.

Disrupting protein expression with Peptide Nucleic Acids reduces infection by obligate intracellular Rickettsia.

Peptide Nucleic Acids (PNAs) are single-stranded synthetic nucleic acids with a pseudopeptide backbone in lieu of the phosphodiester linked sugar and phosphate found in traditional oligos. PNA designed complementary to the bacterial Shine-Dalgarno or start codon regions of mRNA disrupts translation resulting in the transient reduction in protein expression. This study examines the use of PNA technology to interrupt protein expression in obligate intracellular Rickettsia sp.

Secretome of obligate intracellular Rickettsia.

The genus Rickettsia (Alphaproteobacteria, Rickettsiales, Rickettsiaceae) is comprised of obligate intracellular parasites, with virulent species of interest both as causes of emerging infectious diseases and for their potential deployment as bioterrorism agents. Currently, there are no effective commercially available vaccines, with treatment limited primarily to tetracycline antibiotics, although others (e.g.

Rickettsia typhi possesses phospholipase A2 enzymes that are involved in infection of host cells.

The long-standing proposal that phospholipase A2 (PLA2) enzymes are involved in rickettsial infection of host cells has been given support by the recent characterization of a patatin phospholipase (Pat2) with PLA2 activity from the pathogens Rickettsia prowazekii and R. typhi. However, pat2 is not encoded in all Rickettsia genomes; yet another uncharacterized patatin (Pat1) is indeed ubiquitous.

Surface proteome analysis and characterization of surface cell antigen (Sca) or autotransporter family of Rickettsia typhi.

Surface proteins of the obligate intracellular bacterium Rickettsia typhi, the agent of murine or endemic typhus fever, comprise an important interface for host-pathogen interactions including adherence, invasion and survival in the host cytoplasm. In this report, we present analyses of the surface exposed proteins of R. typhi based on a suite of predictive algorithms complemented by experimental surface-labeling with thiol-cleavable sulfo-NHS-SS-biotin and identification of labeled peptides by LC MS/MS.

TolC-dependent secretion of an ankyrin repeat-containing protein of Rickettsia typhi.

Rickettsia typhi, the causative agent of murine (endemic) typhus, is an obligate intracellular pathogen with a life cycle involving both vertebrate and invertebrate hosts. In this study, we characterized a gene (RT0218) encoding a C-terminal ankyrin repeat domain-containing protein, named Rickettsia ankyrin repeat protein 1 (RARP-1), and identified it as a secreted effector protein of R. typhi.

Phase IV trial of miltefosine in adults and children for treatment of visceral leishmaniasis (kala-azar) in Bangladesh.

Miltefosine (target dose of 2.5 mg/kg/day for 28 days) is the recommended treatment for visceral leishmaniasis (kala-azar) in Bangladesh on the basis of data from India. We evaluated miltefosine in a phase IV trial of 977 patients in Bangladesh.

A Kunitz protease inhibitor from Dermacentor variabilis, a vector for spotted fever group rickettsiae, limits Rickettsia montanensis invasion.

A defining facet of tick-Rickettsia symbioses is the molecular strategy employed by each partner to ensure its own survival. Ticks must control rickettsial colonization to avoid immediate death. In the current study, we show that rickettsial abundance in the tick midgut increases once the expression of a Kunitz-type serine protease inhibitor from the American dog tick (Dermacentor variabilis) (DvKPI) is suppressed by small interfering RNA (siRNA).