The characterization and manipulation of the bacterial microbiome of the Rocky Mountain wood tick, Dermacentor andersoni

BACKGROUND: In North America, ticks are the most economically impactful vectors of human and animal pathogens. The Rocky Mountain wood tick, Dermacentor andersoni (Acari: Ixodidae), transmits Rickettsia rickettsii and Anaplasma marginale to humans and cattle, respectively. In recent years, studies have shown that symbiotic organisms are involved in a number of biochemical and physiological functions. Characterizing the bacterial microbiome of D. andersoni is a pivotal step towards understanding symbiont-host interactions. FINDINGS: In this study, we have shown by high-throughput sequence analysis that the composition of endosymbionts in the midgut and salivary glands in adult ticks is dynamic over three generations. Four Proteobacteria genera, Rickettsia, Francisella, Arsenophonus, and Acinetobacter, were identified as predominant symbionts in these two tissues. Exposure to therapeutic doses of the broad-spectrum antibiotic, oxytetracycline, affected both proportions of predominant genera and significantly reduced reproductive fitness. Additionally, Acinetobacter, a free-living ubiquitous microbe, invaded the bacterial microbiome at different proportions based on antibiotic treatment status suggesting that microbiome composition may have a role in susceptibility to environmental contaminants. CONCLUSIONS: This study characterized the bacterial microbiome in D. andersoni and determined the generational variability within this tick. Furthermore, this study confirmed that microbiome manipulation is associated with tick fitness and may be a potential method for biocontrol

Eradication of Staphylococcus aureus Biofilm Infection by Persister Drug Combination

Staphylococcus aureus can cause a variety of infections, including persistent biofilm infections, which are difficult to eradicate with current antibiotic treatments. Here, we demonstrate that combining drugs that have robust anti-persister activity, such as clinafloxacin or oritavancin, in combination with drugs that have high activity against growing bacteria, such as vancomycin or meropenem, could completely eradicate S. aureus biofilm bacteria in vitro. In contrast, single or two drugs, including the current treatment doxycycline plus rifampin for persistent S. aureus infection, failed to kill all biofilm bacteria in vitro. In a chronic persistent skin infection mouse model, we showed that the drug combination clinafloxacin + meropenem + daptomycin which killed all biofilm bacteria in vitro completely eradicated S. aureus biofilm infection in mice while the current treatments failed to do so. The complete eradication of biofilm bacteria is attributed to the unique high anti-persister activity of clinafloxacin, which could not be replaced by other fluoroquinolones including moxifloxacin, levofloxacin, or ciprofloxacin. We also compared our persister drug combination with the current approaches for treating persistent infections, including gentamicin + fructose and ADEP4 + rifampin in the S. aureus biofilm infection mouse model, and found neither treatment could eradicate the biofilm infection. Our study demonstrates an important treatment principle, the Yin–Yang model, for persistent infections by targeting both growing and non-growing heterogeneous bacterial populations, utilizing persister drugs for the more effective eradication of persistent and biofilm infections. Our findings have implications for the improved treatment of other persistent and biofilm infections in general

Laboratory colonization stabilizes the naturally dynamic microbiome composition of field collected Dermacentor andersoni ticks

Abstract Background Nearly a quarter of emerging infectious diseases identified in the last century are arthropod-borne. Although ticks and insects can carry pathogenic microorganisms, non-pathogenic microbes make up the majority of their microbial communities. The majority of tick microbiome research has had a focus on discovery and description; very few studies have analyzed the ecological context and functional responses of the bacterial microbiome of ticks. The goal of this analysis was to characterize the stability of the bacterial microbiome of Dermacentor andersoni ticks between generations and two populations within a species. Methods The bacterial microbiome of D. andersoni midguts and salivary glands was analyzed from populations collected at two different ecologically distinct sites by comparing field (F1) and lab-reared populations (F1-F3) over three generations. The microbiome composition of pooled and individual samples was analyzed by sequencing nearly full-length 16S rRNA gene amplicons using a Pacific Biosciences CCS platform that allows identification of bacteria to the species level. Findings In this study, we found that the D. andersoni microbiome was distinct in different geographic populations and was tissue specific, differing between the midgut and the salivary gland, over multiple generations. Additionally, our study showed that the microbiomes of laboratory-reared populations were not necessarily representative of their respective field populations. Furthermore, we demonstrated that the microbiome of a few individual ticks does not represent the microbiome composition at the population level. Conclusions We demonstrated that the bacterial microbiome of D. andersoni was complex over three generations and specific to tick tissue (midgut vs. salivary glands) as well as geographic location (Burns, Oregon vs. Lake Como, Montana vs. laboratory setting). These results provide evidence that habitat of the tick population is a vital component of the complexity of the bacterial microbiome of ticks, and that the microbiome of lab colonies may not allow for comparative analyses with field populations. A broader understanding of microbiome variation will be required if we are to employ manipulation of the microbiome as a method for interfering with acquisition and transmission of tick-borne pathogens

Fucoidan is a non-anticoagulant inhibitor of intimal hyperplasia

We previously reported that heparin inhibits the proliferation of fibroblasts and vascular smooth muscle cells (SMC), in part, by binding to and increasing the antiproliferative activity of transforming growth factor-β1 (TGF-β1). We now report that certain other polyanions which are structurally distinct from heparin, such as fucoidan and polyinosinic acid, are more avid ligands for TGF-β1 and more potent antiproliferative agents than heparin. Fucoidan possessed more potent antiproliferative activity than heparin against rat and bovine aortic SMC in vitro, though possessing much lower anticoagulant activity than heparin. Furthermore, fucoidan suppressed in vivo intimal hyperplasia when continuously infused into rats subjected to balloon-catheter injury. Unlike heparin, which also suppressed intimal hyperplasia, fucoidan did not cause systemic anticoagulation. Thus, fucoidan may be useful as a non-anticoagulant inhibitor of post-angioplasty intimal hyperplasia. © 1992

Pregnant women´s perceptions of information about alcohol use during pregnancy: a qualitative pilot study

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