Tick-transmitted rickettsial diseases, such as ehrlichiosis and spotted fever rickettsiosis, are significant sources of morbidity and mortality in the southern United States. Because of their exposure in tick-infested woodlands, outdoor workers experience an increased risk of infection with tick-borne pathogens. As part of a double blind randomized-controlled field trial of the effectiveness of permethrin-treated clothing in preventing tick bites, we identified tick species removed from the skin of outdoor workers in North Carolina and tested the ticks for Rickettsiales pathogens. Ticks submitted by study participants from April-September 2011 and 2012 were identified to species and life stage, and preliminarily screened for the genus Rickettsia by nested PCR targeting the 17-kDa protein gene. Rickettsia were further identified to species by PCR amplification of 23S-5S intergenic spacer (IGS) fragments combined with reverse line blot hybridization with species-specific probes and through cloning and nucleotide sequence analysis of 23S-5S amplicons. Ticks were examined for Ehrlichia and Anaplasma by nested PCR directed at the gltA, antigen-expressing gene containing a variable number of tandem repeats, 16S rRNA, and groESL genes. The lone star tick (Amblyomma americanum) accounted for 95.0 and 92.9% of ticks submitted in 2011 (n = 423) and 2012 (n = 451), respectively. Specimens of American dog tick (Dermacentor variabilis), Gulf Coast tick (Amblyomma maculatum) and black-legged tick (Ixodes scapularis) were also identified. In both years of our study, 60.9% of ticks tested positive for 17-kDa. "Candidatus Rickettsia amblyommii", identified in all four tick species, accounted for 90.2% (416/461) of the 23S-5S-positive samples and 52.9% (416/787) of all samples tested. Nucleotide sequence analysis of Rickettsia-specific 23S-5S IGS, ompA and gltA gene fragments indicated that ticks, principally A. americanum, contained novel species of Rickettsia. Other Rickettsiales, including Ehrlichia ewingii, E. chaffeensis, Ehrlichia sp. (Panola Mountain), and Anaplasma phagocytophilum, were infrequently identified, principally in A. americanum. We conclude that in North Carolina, the most common rickettsial exposure is to R. amblyommii carried by A. americanum. Other Rickettsiales bacteria, including novel species of Rickettsia, were less frequently detected in A. americanum but are relevant to public health nevertheless.
The response of the retina to ischemic insult typically leads to aberrant retinal neovascularization, a major cause of blindness. The epigenetic regulation of angiogenic gene expression by miRNAs provides new prospects for their therapeutic utility in retinal neovascularization. Here, we focus on miR-155, a microRNA functionally important in inflammation, which is of paramount importance in the pathogenesis of retinal neovascularization. Whereas constitutive miR-155-deficiency in mice results in mild vascular defects, forced expression of miR-155 causes endothelial hyperplasia and increases microglia count and activation. The mouse model of oxygen-induced retinopathy, which recapitulates ischemia-induced aberrant neovessel growth, is characterized by increased expression of miR-155 and localized areas of microglia activation. Interestingly, miR-155 deficiency in mice reduces microglial activation, curtails abnormal vessel growth, and allows for rapid normalization of the retinal vasculature following ischemic insult. miR-155 binds to the 3′-UTR and represses the expression of the CCN1 gene, which encodes an extracellular matrix-associated integrin-binding protein that both promotes physiological angiogenesis and harnesses growth factor-induced abnormal angiogenic responses. Single CCN1 deficiency or double CCN1 and miR-155 knock-out in mice causes retinal vascular malformations typical of faulty maturation, mimicking the vascular alterations of miR-155 gain of function. During development, the miR-155/CCN1 regulatory axis balances the proangiogenic and proinflammatory activities of microglia to allow for their function as guideposts for sprout fusion and anastomosis. Under ischemic conditions, dysregulated miR-155 and CCN1 expression increases the inflammatory load and microglial activation, prompting aberrant angiogenic responses. Thus, miR-155 functions in tandem with CCN1 to modulate inflammation-induced vascular homeostasis and repair.
Listeria monocytogenes is a Gram-positive pathogen responsible for the severe foodborne disease listeriosis. A chromosomal hotspot between lmo0301 and lmo0305 has been noted to harbor diverse restriction modification (RM) systems. Here, we analyzed 872 L. monocytogenes genomes to better understand the prevalence and types of RM systems in this region, designated the immigration control region (ICR). Type I, II, III and IV RM systems were found in 86.1% of strains inside the ICR and in 22.5% of strains flanking the ICR. ICR content was completely conserved within the same multilocus sequence typing-based sequence type (ST), but the same RM system could be identified in diverse STs. The intra-ST conservation of ICR content suggests that this region may drive the emergence of new STs and promote clone stability. Sau3AI-like, LmoJ2 and LmoJ3 type II RM systems as well as type I EcoKI-like, and type IV AspBHI-like and mcrB-like systems accounted for all RM systems in the ICR. A Sau3AI-like type II RM system with specificity for GATC was harbored in the ICR of many STs, including all strains of the ancient, ubiquitous ST1. The extreme paucity of GATC recognition sites in lytic phages may reflect ancient adaptation of these phages to preempt resistance associated with the widely distributed Sau3AI-like systems. These findings indicate that the ICR has a high propensity for RM systems which are intraclonaly conserved and may impact bacteriophage susceptibility as well as ST emergence and stability.
Significance The South Coast Air Basin of California, a region of 16.8 million people, is among the most polluted air basins in the United States. A multidecadal effort to attain federal air-quality standards has led to significant progress, but much more work remains. Are recently implemented statewide building efficiency standards on rooftops counterproductive to these goals? With comprehensive regional models and intensive development of model input parameters, our research has identified the air-quality consequences that are expected to result from these efficiency standards. The results can inform policies to mitigate some air-quality penalties, while preserving the benefits of building efficiency standards. This work also sheds light on potential future policies aimed at reducing urban heating from pavement surfaces.
Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans with severe symptoms. In South Korea, listeriosis had only been reported sporadically among hospitalized patients until the first foodborne outbreak occurred in 2018. In this study, a L. monocytogenes strain responsible for this outbreak (FSCNU0110) was characterized via whole genome sequencing and compared with publicly available L. monocytogenes genomes of the same clonal complex (CC). Strain FSCNU0110 belonged to multilocus sequence typing (MLST)-based sequence type 224 and CC224, and core genome MLST-based sublineage 6,178. The strain harbored tetracycline resistance gene tetM, four other antibiotic resistance genes, and 64 virulence genes, including Listeria pathogenicity island 1 (LIPI-1) and LIPI-3. Interestingly, llsX in LIPI-3 exhibited a characteristic SNP (deletion of A in position 4, resulting in a premature stop codon) that was missing among all CC224 strains isolated overseas but was conserved among those from South Korea. In addition, the tetM gene was also detected only in a subset of CC224 strains from South Korea. These findings will provide an essential basis for assessing the characteristics of CC224 strains in South Korea that have shown a potential to cause listeriosis outbreaks.
Intestinal microbiota exerts protective effects against the infection of various bacterial pathogens, including Listeria monocytogenes, a major foodborne pathogen whose infection can lead to a disease (listeriosis) with a high fatality rate. As a strategy to mitigate the action of the intestinal microbiota, pathogens often produce antimicrobial proteinaceous compounds such as bacteriocins. In this review, we summarize the information currently available for the well-characterized L. monocytogenes bacteriocin listeriolysin S, with the emphasis on its intriguing mode of action as a virulence factor, which promotes the infection of L. monocytogenes by changing the composition of the intestinal microbiota. We then discuss another intriguing L. monocytogenes bacteriocin Lmo2776 that specifically inhibits the inflammogenic species, Prevotella copri, in the intestinal microbiota, reducing superfluous inflammation while weakening virulence. In addition, we describe relatively less studied phage tail-like Listeria bacteriocins (monocins) and elaborate on the possibility that these monocins could be involved in enhancing pathogenicity. In spite of the burgeoning interest in the roles played by the intestinal microbiota against the L. monocytogenes infection, our understanding on the virulence factors affecting the intestinal microbiota is still lacking, calling for further studies on bacteriocins that could function as novel virulence factors.
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