Pathogenic landscape of transboundary zoonotic diseases in the Mexico–US border along the Rio Grande

Transboundary zoonotic diseases, several of which are vector borne, can maintain a dynamic focus and have pathogens circulating in geographic regions encircling multiple geopolitical boundaries. Global change is intensifying transboundary problems, including the spatial variation of the risk and incidence of zoonotic diseases.The complexity of these challenges can be greater in areas where rivers delineate international boundaries and encompass transitions between ecozones.The Rio Grande serves as a natural border between the US State ofTexas and the Mexican States of Chihuahua, Coahuila, Nuevo León, andTamaulipas. Not only do millions of people live in this transboundary region, but also a substantial amount of goods and people pass through it everyday. Moreover, it occurs over a region that functions as a corridor for animal migrations, and thus links the Neotropic and Nearctic biogeographic zones, with the latter being a known foci of zoonotic diseases. However, the pathogenic landscape of important zoonotic diseases in the southTexas–Mexico transboundary region remains to be fully understood. An international perspective on the interplay between disease systems, ecosystem processes, land use, and human behaviors is applied here to analyze landscape and spatial features of Venezuelan equine encephalitis, Hantavirus disease, Lyme Borreliosis, Leptospirosis, Bartonellosis, Chagas disease, human Babesiosis, and Leishmaniasis. Surveillance systems following the One Health approach with a regional perspective will help identifying opportunities to mitigate the health burden of those diseases on human and animal populations. It is proposed that the Mexico–US border along the Rio Grande region be viewed as a continuum landscape where zoonotic pathogens circulate regardless of national borders

Mechanosensing uses the intricate internal organization of bacteria to regulate surface behaviors

Bacteria use conserved signal transduction pathways, called sensory systems, to sense environmental stimuli. Most of our understanding of sensory systems in bacteria, however, comes from the chemotaxis system of Escherichia coli, which senses chemical gradients to control the direction of flagellar-based motility (chemosensing). Importantly, bacteria can also sense mechanical stimuli to actively shape their physiology. An in-depth mechanistic understanding of mechanosensory systems, when compared to their chemosensory counterparts, is however lacking. This dissertation presents work towards understanding mechanosensing in the important opportunistic human pathogen Pseudomonas aeruginosa. This Gram-negative bacterium uses Type IV pili (TFP), retractile polarly localized appendages, to sense mechanical forces generated during surface contact at one cell pole. We and others have demonstrated that spatially resolved mechanical stimuli transmitted by TFP activates the Pil-Chp mechanosensory system. Upon surface contact, TFP transmits mechanical stimuli to the Pil-Chp receptor, PilJ, thereby altering the autophosphorylation state of ChpA and thus the phosphorylation of PilG and PilH, the antagonistic Pil-Chp response regulators. PilG and PilH inversely control two outputs of the Pil-Chp system in P. aeruginosa: cAMP production and twitching motility. Sensing of surface contact by the Pil-Chp system activates the membrane bound CyaB adenylate cyclase, which catalyzes the production of the second messenger, cyclic adenosine monophosphate (cAMP). cAMP binds to the Vfr transcription factor, leading to altered transcription of >200 genes involved in acute virulence as well as selected TFP regulatory proteins. Signal processing through PilG and PilH is critical for surface-dependent cAMP production. PilG promotes cAMP production and upregulation of the surface dependent transcriptional program while PilH has the opposite effect. The Pil-Chp mechanosensory system is required for twitching motility, partially independently of cAMP levels. In Chapter 2, we demonstrate that P. aeruginosa actively directs twitching in the direction of mechanical input from TFP, in a process called mechanotaxis. The Pil-Chp system controls the balance of forward and reverse twitching motility of single cells in response to the mechanical inputs. We show that the Pil-Chp response regulators PilG and PilH control the polarization of the TFP extension motor PilB. PilG localizes to both poles, but shows greater accumulation at the leading pole, where it stimulates polarization favoring forward migration. In contrast, PilH, is primarily cytoplasmic, thereby globally antagonizing PilG. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. The distinct localization of response regulators establishes a signaling landscape known as local-excitation, global-inhibition in higher order organisms.In Chapter 3, we demonstrate that PilG and PilH enable dynamic cell polarization by coupling their antagonistic functions on TFP extension. By precisely quantifying the localization of fluorescent protein fusions, we show that phosphorylation of PilG by the histidine kinase ChpA controls PilG polarization. Although PilH is not inherently required for twitching reversals, upon phosphorylation, PilH becomes activated and breaks the local positive feedback established by PilG so that forward-twitching cells can reverse. To spatially resolve mechanical signals, the Pil-Chp system thus locally transduces signals with a main output response regulator, PilG. To respond to signal changes, Chp uses its second regulator, PilH, to break the local feedback. In Chapter 4, we report the mechanism of sensory adaptation in the Pil-Chp mechanosensory system. Bacterial sensory adaptation has primarily been studied in flagellar-mediated chemotaxis, where reversible methylation of sensory receptors by a methyltransferase and a methylesterase “tune” their sensitivity of signaling. The Pil-Chp system encodes the PilK methyltransferase, predicted to methylate PilJ, and the ChpB methylesterase, predicted to demethylate PilJ; however, whether sensory adaptation occurs in response to surface contact remained underexplored. Using biochemistry, genetics, and cell biology, we discovered that PilK and ChpB are segregated to opposing cell poles as P. aeruginosa explore surfaces. By coordinating the localization of both enzymes, we found that the Pil-Chp response regulators influence local PilJ methylation in vivo. We propose a model in which spatially resolved mechanical inputs transmitted by TFP not only alter PilG and PilH signaling mechanisms but locally controls PilJ methylation to modulate twitching motility reversal rates and surface-dependent cAMP production. Despite decades of chemosensory adaptation studies, our work has uncovered an unrecognized mechanism that bacteria use to achieve adaptation to mechanical sensory stimuli.Acinetobacter species are opportunistic pathogens that are ubiquitous throughout the environment and are emerging as a public health threat around the world due to their widespread multidrug resistance. Intriguingly, many Acinetobacter strains encode homologs of the P. aeruginosa Pil-Chp mechanosensory system. In Chapter 5, we demonstrate that A. nosocomialis strain M2, a pathogenic member of the Acinetobacter calcoaceticus-baumannii complex, has a robust surface-dependent transcriptional response. We speculate that the homologous Pil-Chp mechanosensory system is responsible for the surface-dependent transcriptional response that we report in this dissertation. Overall, this dissertation demonstrates that mechanosensing through the Pil-Chp system takes advantage of the intricate internal organization of bacteria to sense spatially resolved mechanical information. As medically Acinetobacter species exhibit a surface transcriptional response, defining the mechanosensing mechanism of Acinetobacter species represents an exciting area of investigation. Understanding the mechanisms of bacterial mechanosensing may lead to the generation of desperately needed therapeutics to treat multi-drug resistant infections, such as the ones typically caused by P. aeruginosa and medically relevant Acinetobacter species

Chitosan: Biocontrol agent of Fusarium oxysporum in tomato fruit (Solanum lycopersicum L.)

Synthetic fungicides have experienced a significant increase in recent years, necessitating the search for more sustainable and environmentally friendly alternatives. In this regard, chitosan has emerged as an option to reduce reliance on these products. This study evaluated the effect of chitosan as a biocontrol agent against Fusarium oxysporum in tomato fruits. A fully randomized experimental design incorporating 6 treatments was employed, consisting of four chitosan treatments (0.5, 1, 2, and 3 g L-1), a negative control involving the application of a synthetic fungicide, and a positive control inoculated with F. oxysporum. Samples were taken from infected tomato fruits. The F4 isolate of Fusarium sp. was identified as F. oxysporum, and demonstrated the highest level of virulence. Among the four chitosan treatments, the 3 g L-1 treatment showed the highest a percentage of mycelial growth inhibition (PMGI) at 79.92% and the greatest reduction in biomass at 0.65 g, which did not differ significantly from the synthetic fungicide. Regarding disease severity and incidence, there were significant variations among each of the chitosan treatments, with the highest results obtained with the 2 and 3 g L-1 treatments. All chitosan treatments reduced disease severity in tomato fruits. Applying chitosan on fruits of the tomato plant presents an alternative for diminishing reliance on synthetic fungicides

Mechanotaxis directs Pseudomonas aeruginosa twitching motility.

The opportunistic pathogen Pseudomonas aeruginosa explores surfaces using twitching motility powered by retractile extracellular filaments called type IV pili (T4P). Single cells twitch by sequential T4P extension, attachment, and retraction. How single cells coordinate T4P to efficiently navigate surfaces remains unclear. We demonstrate that P. aeruginosa actively directs twitching in the direction of mechanical input from T4P in a process called mechanotaxis. The Chp chemotaxis-like system controls the balance of forward and reverse twitching migration of single cells in response to the mechanical signal. Collisions between twitching cells stimulate reversals, but Chp mutants either always or never reverse. As a result, while wild-type cells colonize surfaces uniformly, collision-blind Chp mutants jam, demonstrating a function for mechanosensing in regulating group behavior. On surfaces, Chp senses T4P attachment at one pole, thereby sensing a spatially resolved signal. As a result, the Chp response regulators PilG and PilH control the polarization of the extension motor PilB. PilG stimulates polarization favoring forward migration, while PilH inhibits polarization, inducing reversal. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. The distinct localization of response regulators establishes a signaling landscape known as local excitation-global inhibition in higher-order organisms, identifying a conserved strategy to transduce spatially resolved signals

One Health Interactions of Chagas Disease Vectors, Canid Hosts, and Human Residents along the Texas-Mexico Border.

BACKGROUND:Chagas disease (Trypanosoma cruzi infection) is the leading cause of non-ischemic dilated cardiomyopathy in Latin America. Texas, particularly the southern region, has compounding factors that could contribute to T. cruzi transmission; however, epidemiologic studies are lacking. The aim of this study was to ascertain the prevalence of T. cruzi in three different mammalian species (coyotes, stray domestic dogs, and humans) and vectors (Triatoma species) to understand the burden of Chagas disease among sylvatic, peridomestic, and domestic cycles. METHODOLOGY/PRINCIPAL FINDINGS:To determine prevalence of infection, we tested sera from coyotes, stray domestic dogs housed in public shelters, and residents participating in related research studies and found 8%, 3.8%, and 0.36% positive for T. cruzi, respectively. PCR was used to determine the prevalence of T. cruzi DNA in vectors collected in peridomestic locations in the region, with 56.5% testing positive for the parasite, further confirming risk of transmission in the region. CONCLUSIONS/SIGNIFICANCE:Our findings contribute to the growing body of evidence for autochthonous Chagas disease transmission in south Texas. Considering this region has a population of 1.3 million, and up to 30% of T. cruzi infected individuals developing severe cardiac disease, it is imperative that we identify high risk groups for surveillance and treatment purposes

Pathogenic Landscape of Transboundary Zoonotic Diseases in the Mexico–US Border Along the Rio Grande

Transboundary zoonotic diseases, several of which are vector borne, can maintain a dynamic focus, and have pathogens circulating in geographic regions encircling multiple geopolitical boundaries. Global change is intensifying transboundary problems including the spatial variation of the risk and incidence of zoonotic diseases. The complexity of these challenges can be greater in areas where rivers delineate international boundaries and encompass transitions between ecozones. The Rio Grande serves as a natural border between the US State of Texas and the Mexican States of Chihuahua, Coahuila, Nuevo León, and Tamaulipas. Not only millions of people live in this transboundary region but also a substantial movement of goods and people pass through it everyday. Moreover, it occurs over a region that functions as a corridor for animal migrations, and thus links the Neotropic and Nearctic biogeographic zones, with the latter being a known foci of zoonotic diseases. However, the pathogenic landscape of important zoonotic diseases in the south Texas-Mexico transboundary region remains to be fully understood. An international perspective on the interplay between disease systems, ecosystem processes, land use, and human behaviors is applied here to analyze landscape and spatial features of Venezuelan equine encephalitis, Hantavirus disease, Lyme Borreliosis, Leptospirosis, Bartonellosis, Chagas disease, human Babesiosis, and Leishmaniasis. Surveillance systems following the One Health approach with a regional perspective will help identifying opportunities to mitigate the health burden of those diseases on human and animal populations. It is proposed that the Mexico-US border, along the Rio Grande region be viewed as a continuum landscape where zoonotic pathogens circulate regardless of national borders

Bioeconomy. New framework for sustainable growth in Latin America

La bioeconomía constituye una estrategia basada en la idea de un uso más eficiente de los recursos, tecnologías y procesos biológicos para la provisión de bienes y servicios que nuestras sociedades demandan. Rápidamente está evolucionado hacia una visión amplia para el desarrollo sostenible que no solo se trata del aprovechamiento de los nuevos conocimientos y tecnologías que convergen y se potencian entre sí para ofrecer nuevas opciones impensadas como posibles hasta hace muy poco tiempo, sino también de un cambio total del papel de los recursos biológicos en la estructuración de las economías y la búsqueda de bienestar social. Para los países de América Latina y el Caribe estas tendencias representan una nueva y potente oportunidad. La región no solo es un gran productor de biomasa sostenible, también cuenta con importantes desarrollos en sus capacidades científico-tecnológicas, así como en su infraestructura industrial y en el desarrollo de la bioenergía, donde se ha transformado en uno de los principales actores en los mercados internacionales. Este libro presenta ejemplos de diferentes enfoques, así como algunas experiencias de países de América Latina que transitan hacia la construcción de una estrategia nacional específicamente dedicada a la bioeconomía.Bogot

<i>Trypanosoma Cruzi</i> (Chagas Disease) Positive Samples By Species And Geographic Origin.

<p><i>Trypanosoma Cruzi</i> (Chagas Disease) Positive Samples By Species And Geographic Origin.</p

<i>Trypanosoma Cruzi</i> (Chagas Disease) Prevalence In Coyotes, Shelter Dogs, Human Residents, And Vectors Of South Texas.

<p><i>Trypanosoma Cruzi</i> (Chagas Disease) Prevalence In Coyotes, Shelter Dogs, Human Residents, And Vectors Of South Texas.</p

Enabling genetic analysis of diverse bacteria with Mobile-CRISPRi

The vast majority of bacteria, including human pathogens and microbiome species, lack genetic tools needed to systematically associate genes with phenotypes. This is the major impediment to understanding the fundamental contributions of genes and gene networks to bacterial physiology and human health. Clustered regularly interspaced short palindromic repeats interference (CRISPRi), a versatile method of blocking gene expression using a catalytically inactive Cas9 protein (dCas9) and programmable single guide RNAs, has emerged as a powerful genetic tool to dissect the functions of essential and non-essential genes in species ranging from bacteria to humans 1–6 . However, the difficulty of establishing effective CRISPRi systems across bacteria is a major barrier to its widespread use to dissect bacterial gene function. Here, we establish ‘Mobile-CRISPRi’, a suite of CRISPRi systems that combines modularity, stable genomic integration and ease of transfer to diverse bacteria by conjugation. Focusing predominantly on human pathogens associated with antibiotic resistance, we demonstrate the efficacy of Mobile-CRISPRi in gammaproteobacteria and Bacillales Firmicutes at the individual gene scale, by examining drug–gene synergies, and at the library scale, by systematically phenotyping conditionally essential genes involved in amino acid biosynthesis. Mobile-CRISPRi enables genetic dissection of non-model bacteria, facilitating analyses of microbiome function, antibiotic resistances and sensitivities, and comprehensive screens for host–microorganism interactions