18 research outputs found
Control of Pyrethroid-Resistant Chagas Disease Vectors with Entomopathogenic Fungi
Chagas disease, also known as American Trypanosomiasis, is the most relevant parasitic disease in Latin America, being a major burden that affects mostly poor human populations living in rural areas. The kissing-bugs of the Triatominae family transmit the parasite Trypanosoma cruzi by infectious blood-sucking; Triatoma infestans is the vector of major relevance in the southern Cone of South America. Current control strategies, heavily based on residual insecticide spraying, are threatened by the emergence of pyrethroid-resistant bug populations. Furthermore, ensuring the long-term and sustainable control of this overwhelming disease remains a major challenge. Here we show the utility of a simple, low-cost, biological control methodology against T. infestans bugs, regardless of their susceptibility to pyrethroid insecticides. It is based on the understanding of the initial contact interactions between a mycoinsecticide agent—the fungus Beauveria bassiana—and the host defense barrier, the bug cuticle. The proposed methodology is also supported by present data showing a relationship between the triatomine cuticle width and its hydrocarbon surface components, with insecticide resistance. These results will help to provide a safe and efficient alternative to overcome pyrethroid-resilience of these noxious bugs. A high transfer potential to immediate application in rural communities located in remote areas inaccessible to sanitary control teams, and to the control of other Chagas disease vectors as well, is also envisaged
Transcriptome Analysis of Neisseria meningitidis in Human Whole Blood and Mutagenesis Studies Identify Virulence Factors Involved in Blood Survival
During infection Neisseria meningitidis (Nm) encounters multiple
environments within the host, which makes rapid adaptation a crucial factor for
meningococcal survival. Despite the importance of invasion into the bloodstream
in the meningococcal disease process, little is known about how Nm adapts to
permit survival and growth in blood. To address this, we performed a time-course
transcriptome analysis using an ex vivo model of human whole
blood infection. We observed that Nm alters the expression of ≈30% of
ORFs of the genome and major dynamic changes were observed in the expression of
transcriptional regulators, transport and binding proteins, energy metabolism,
and surface-exposed virulence factors. In particular, we found that the gene
encoding the regulator Fur, as well as all genes encoding iron uptake systems,
were significantly up-regulated. Analysis of regulated genes encoding for
surface-exposed proteins involved in Nm pathogenesis allowed us to better
understand mechanisms used to circumvent host defenses. During blood infection,
Nm activates genes encoding for the factor H binding proteins, fHbp and NspA,
genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as
several less characterized surface-exposed proteins that might have a role in
blood survival. Through mutagenesis studies of a subset of up-regulated genes we
were able to identify new proteins important for survival in human blood and
also to identify additional roles of previously known virulence factors in
aiding survival in blood. Nm mutant strains lacking the genes encoding the
hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and
NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate
permease LctP were sensitive to killing by human blood. This increased knowledge
of how Nm responds to adaptation in blood could also be helpful to develop
diagnostic and therapeutic strategies to control the devastating disease cause
by this microorganism