Positive rates of virulence genes vary remarkably in . Genes , and were primary ones inducing Hv- (+)-KP. IncHI1B plasmids carrying virulence genes and IncFII ones with constitute the primary combination responsible for Hv- (+)-KP. The making of Hv- (+)-KP is mostly (+)-KP acquiring another plasmid harboring virulence genes.Positive rates of virulence genes vary remarkably in K. pneumoniae. Genes iucA, p-rmpA2 and p-rmpA were primary ones inducing Hv-bla KPC(+)-KP. IncHI1B plasmids carrying virulence genes and IncFII ones with bla KPC constitute the primary combination responsible for Hv-bla KPC(+)-KP. The making of Hv-bla KPC(+)-KP is mostly via bla KPC(+)-KP acquiring another plasmid harboring virulence genes.Salmonella Typhi is a human-restricted bacterial pathogen that causes typhoid fever, a life-threatening systemic infection. A fundamental aspect of S. Typhi pathogenesis is its ability to survive in human macrophages but not in macrophages from other animals (i.e. mice). Despite the importance of macrophages in establishing systemic S. Typhi infection, the mechanisms that macrophages use to control the growth of S. Typhi and the role of these mechanisms in the bacterium's adaptation to the human host are mostly unknown. To facilitate unbiased identification of genes involved in controlling the growth of S. Typhi in macrophages, we report optimized experimental conditions required to perform loss-of function pooled shRNA screens in primary mouse bone-marrow derived macrophages. Following infection with a fluorescent-labeled S. Typhi, infected cells are sorted based on the intensity of fluorescence (i.e. number of intracellular fluorescent bacteria). shRNAs enriched in the fluorescent population are identified by next-generation sequencing. A proof-of-concept screen targeting the mouse Rab GTPases confirmed Rab32 as important to restrict S. Typhi in mouse macrophages. Interestingly and rather unexpectedly, this screen also revealed that Rab1b controls S. Typhi growth in mouse macrophages. This constitutes the first report of a Rab GTPase other than Rab32 involved in S. Typhi host-restriction. The methodology described here should allow genome-wide screening to identify mechanisms controlling the growth of S. Typhi and other intracellular pathogens in primary immune cells.Plasmodium, the unicellular parasite that causes malaria, evolved a highly unusual mode of reproduction. During its complex life cycle, invasive or transmissive stages alternate with proliferating stages, where a single parasite can produce tens of thousands of progeny. In the clinically relevant blood stage of infection, the parasite replicates its genome up to thirty times and forms a multinucleated cell before daughter cells are assembled. selleck chemicals Thus, within a single cell cycle, Plasmodium develops from a haploid to a polypoid cell, harboring multiple copies of its genome. Polyploidy creates several biological challenges, such as imbalances in genome output, and cells can respond to this by changing their size and/or alter the production of RNA species and protein to achieve expression homeostasis. However, the effects and possible adaptations of Plasmodium to the massively increasing DNA content are unknown. Here, we revisit and embed current Plasmodium literature in the context of polyploidy and propose potential mechanisms of the parasite to cope with the increasing gene dosage.Leishmaniasis is a group of heterogenous diseases considered as an important public health problem in several countries. This neglected disease is caused by over 20 parasite species of the protozoa belonging to the Leishmania genus and is spread by the bite of a female phlebotomine sandfly. Depending on the parasite specie and the immune status of the patient, leishmaniasis can present a wide spectrum of clinical manifestations. As an obligate intracellular parasite, Leishmania colonize phagocytic cells, mainly the macrophages that orchestrate the host immune response and determine the fate of the infection. Once inside macrophages, Leishmania triggers different signaling pathways that regulate the immune and metabolic response of the host cells. Various transcription factors regulate such immune-metabolic responses and the associated leishmanicidal and inflammatory reaction against the invading parasite. In this review, we will highlight the most important transcription factors involved in these responses, their interactions and their impact on the establishment and the progression of the immune response along with their effect on the physiopathology of the disease. Mucosal leishmaniasis (ML), the most inflammatory form of tegumentary leishmaniasis, is predominantly caused by . The disease is characterized by the development of lesions, mainly in the nasal mucosa. An exacerbated inflammatory response has been associated with the presence of destructive and disfiguring lesions, with stages of severity ranging from small nodulations to the complete destruction of the nasal pyramid architecture. As is an intracellular parasite, most immunological studies have emphasized the cell-mediated immune response, while relatively few studies aimed to investigate the role antibodies in protection against, or the pathology of ML. Patients with a confirmed diagnosis of ML were classified according to clinical staging criteria. Serum levels of -specific IgG, IgG1 and IgG2 antibodies were determined by ELISA before and after treatment with antimony or antimony plus pentoxifylline. Patients in stages IV and V produced higher concentrations of IgG and IgG1 antibodies when compared to those in stage I and II. Significant reductions were seen in the concentrations of IgG and IgG2 antibodies in most patients who responded well to treatment. Our data demonstrate an association between IgG antibody titers and the severity of mucosal disease. The observed reduction in antibody production after successful treatment in most patients preliminarily indicates that these tests can be used to aid in the assessment of therapeutic response.Our data demonstrate an association between IgG antibody titers and the severity of mucosal disease. The observed reduction in antibody production after successful treatment in most patients preliminarily indicates that these tests can be used to aid in the assessment of therapeutic response.