Chemical Treatment for Colony Collapse Disorder Temporarily Worsens Viral Infections in Honeybees
Acaricide, a chemical used against Varroa mites that infect honeybees, appears to render bees more susceptible to deformed wing virus infections, according to research published in the January issue of the journal Applied and Environmental Microbiology. Like the mites, these viruses have been identified as potential causes of colony collapse disorder.
The Varroa mite is currently the main pathogen linked to colony collapse disorder among European honey bees worldwide. "The mite population grows rapidly, killing colonies within 2-3 years if beekeepers don't remove the mites, which usually involves chemical treatments such as acaricides," says first author Barbara Locke, of the Swedish University of Agricultural Sciences, Uppsala. Nonetheless, she says, the mites kill the colonies not by direct effects, but by transmitting viral infections to the bees.
Deformed wing virus is strongly associated with mite infestations, and the researchers' hypothesized that following acaricide treatment, the virus population would drop along with the mite population. In the study, they treated six bee colonies with Apistan, an acardicide, for six weeks (the standard treatment duration) and left three control colonies untreated, monitoring mite infestation and virus levels weekly.
Contrary to the investigators' hypothesis, the viral infection worsened in the treatment group immediately following acaricide treatment. "This initial increase was seen in all bee stages, including pupae that never were in contact with mites," says Locke. "Thus, we interpreted it to be a possible direct effect of the acaricide, making the bees more susceptible to virus infection," possibly due to either "debilitating direct effects of tau-fluvalinate on honeybee physiology and/or immune system responses," she says, adding that further studies are needed to confirm this result. The virus infections ultimately dropped, slowly, "due to reduced transmission by the mites," says Locke. "However, even at the end of the mite removal treatment, we still recorded substantial infection levels."
Two other viral infections, black queen cell virus, and sac brood virus, were found not to be associated with the mite infestation, says Locke.
"Acaricide treatments are still the most effective method at removing mites from colonies when infestation is high, at colony mortality thresholds," says Locke. "However, this research suggests that for maintaining low infestation, regular alternative control treatments, such as organic methods, could be used for promoting better bee health overall. Further, since the virus is not reduced in the colony as rapidly as the mites are removed, our research underlines the importance of early mite removal to reduce virus levels in overwintering bees, to avoid colony losses."
(B. Locke, E. Forsgren, I. Fries, and J.R. de Miranda, 2012. Acaricide treatment affects viral dynamics in Varroa destructor-infested honey bee colonies via both host physiology and mite control. Appl. Environ. Micriobiol. 78:227-235.)
Saturated Fatty Acids Lead to Mitochondrial Dysfunction and Insulin Resistance
Excessive levels of certain saturated fatty acids cause mitochondria to fragment, leading to insulin resistance in skeletal muscle, a precursor of type 2 diabetes, according to a paper in the January issue of the journal Molecular and Cellular Biology. This is the first time mitochondrial fragmentation has been implicated in insulin resistance, says corresponding author Yau-Sheng Tsai, of the College of Medicine, National Cheng Kung University, Taiwan, Republic of China.
Mitochondria are the intracellular machines that turn sugar into energy, and skeletal muscle is packed with them. Normally, cells respond to insulin, a hormone, by importing glucose from the bloodstream. Type 2 diabetes is characterized by insulin resistance, a cellular impairment in glucose uptake.
The new research offers an explanation for this phenomenon. "Disruption of mitochondrial dynamics may underlie the pathogenesis of muscle insulin resistance in obesity and type 2 diabetes," says Tsai. That explanation suggests a hypothetical treatment. "Manipulating mitochondrial morphology may provide a novel therapeutic strategy for insulin resistance and type 2 diabetes," says Tsai. In the study, the research showed that inhibiting mitochondrial fission in mouse models reduced the insulin resistance, he says.
The study also supports previous research suggesting that reducing saturated fats in the diet would reduce insulin resistance, says Tsai. "It has been well documented that saturated fatty acids can lead to insulin resistance in humans and rodents." Palmitate, a particularly harmful saturated fatty acid, "is very abundant in lard, butter, and margarine," says Tsai.
"Most studies of mitochondria and diabetes have focused on mitochondrial quantity, and they all agree that increasing mitochondrial biogenesis does help mitochondrial function and cellular metabolism," says Tsai. "Our study showed that maintaining the balance of mitochondrial dynamics is also important for mitochondria to maintain normal function."
(H.-F. Jheng, P.-J. Tsai, S.-M. Guo, L.-H. Kuo, C.-S. Chang, I.-J. Su, C.-R. Chang, and Y.-S. Tsai, 2012. Mitochonrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle. Mol. Cell. Biol. 32:309-319.)
H5N1 Virus Targets Pulmonary Endothelial Cells
The H5N1 virus has killed roughly 60 percent of humans infected, a mortality rate which is orders of magnitude higher than that of seasonal influenza virus. Many victims of the former fall heir to acute respiratory distress syndrome—the inability to breathe. Now researchers from the Centers for Disease Control and Prevention, and the University of South Alabama show that the highly pathogenic avian influenza H5N1 virus, but not seasonal influenza viruses, can target the cells of human lung tissue, where they replicate fast and efficiently, and induce inflammation, which correlates with H5N1-induced acute respiratory distress syndrome that is observed in humans. The research is published in the January Journal of Virology.
"The pulmonary endothelium is strategically located within the lung and its function and structural integrity are essential for adequate pulmonary function," says coauthor Terrence Tumpey of the Centers for Disease Control and Prevention. "We compared the infection rate of different subtype influenza viruses in human lung endothelial cells, and assessed the host response to infection," he says. "We found that the H5N1 virus, but not common seasonal influenza viruses, can target human pulmonary endothelial cells." There, the viruses replicate rapidly, creating an overwhelming inflammatory cytokine response, essentially causing an immune response so powerful that it kills the pulmonary endothelial cells, results which Tumpey says correlate with the H5N1-induced acute respiratory distress syndrome that is observed in humans where the production of cytokines, immune system compounds, has been detected in lung endothelial cells.
The Spanish influenza pandemic of 1918 is thought to have resulted in a similarly high influx of inflammatory cells and profound vascular leakage in the lower respiratory tract, often precipitating the same acute respiratory distress syndrome seen in H5N1 influenza cases. That pandemic, estimated to have sickened 350 million, killing roughly 50 million, had a mortality rate of approximately 14 percent—far less than that of H5N1, but still shockingly high.
"Although the mechanism of H5N1 pathogenesis is not entirely known, our research identified one virulent factor, the cleavage site of the viral surface glycoprotein hemagglutinin, which we found to be critical for the production of infectious progeny H5N1 virus in pulmonary endothelial cells," says Tumpey. Other unknown virulence factors undoubtedly exist, and require further study, he says.
"Treatment with anti-inflammatory drugs has been proposed as a therapeutic option for patients infected with H5N1 viruses," says Tumpey. "The development of new, more targeted therapies for H5N1 disease along with combination antiviral drug treatment could be an effective approach in reducing acute lung injury and mortality caused by H5N1 virus."
(H. Zeng, C. Pappas, J.A. Belser, K.V. Houser, W. Zhong, D. A Wadford, T. Stevens, R. Balczon, J.M. Katz, and T.M. Tumpey, 2011. Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. J. Virol. 86:667-678.)
Single Dose of Antibiotic Leaves Mice Highly Vulnerable to Intestinal Infection
Yet another study adds to the growing evidence that antibiotics can disrupt the balance of the intestinal flora, with negative effects on health. A team of researchers from the Memorial Sloan Kettering Cancer Center, New York City, has shown in mouse models that a single dose of the commonly used antibiotic, clindamycin, wiped out nearly 90 percent of bacterial taxa, leaving the mice unusually susceptible to infection by Clostridium difficile, a bacterial pathogen that is innocuous for most health people but that can cause severe diarrhea in individuals following antibiotic treatment. Their research appears in the January issue of the journal Infection and Immunity.
Clindamycin was already known to be "highly associated with the development of Clostridium difficile infections" in humans and mice, says corresponding author Eric G. Pamer. In earlier work, Trevor Lawley had shown that clindamycin administration results in chronic shedding of C. difficile spores by infected mice. The researchers, who included Pamer's colleagues Charlie Buffie and Joao Xavier, hypothesized that "clindamycin-mediated destruction of the complex but stable networks of interacting and interdependent bacterial species [in the intestine] would result in marked instability of the microbiota," that would leave the mice vulnerable to infection, says Pamer, adding that "Our long-term goal is to determine which intestinal bacteria provide resistance to Clostridium difficile infection."
Following the single dose of clindamycin, the investigators "found that mice became highly susceptible to infection and developed severe weight loss, and had a mortality rate of roughly 40 percent," says Pamer. "Surviving mice continued to be infected with C. difficile for 28 days and had persistent bowel inflammation."
Next the team investigated clindamycin's impact on the intestinal microbioata, by isolating the contents of the small intestine and the cecum, and using the "454 deep DNA sequencing platform" to identify species. "To our surprise, roughly 87 percent of the bacterial species that were present prior to antibiotic treatment were undetectable following clindamycin administration, a loss of diversity that persisted for the 28 day duration of this study," says Pamer. During this time, the bacterial species composition fluctuated wildly.
The study demonstrates how the application of deep sequencing platforms to analyze complex microbial populations, such as those that inhabit the human gut can lead to understanding, and perhaps predicting susceptibility to infection by highly antibiotic resistant bacteria, such as C. difficile or vancomycin resistant Enterococcus, says Pamer.
The research was largely supported by the Tow Foundation, which provided a grant to support the Lucille Castori Center for Microbes, Inflammation, and Cancer at Memorial Sloan-Kettering Cancer Center.
(C.G. Buffie, I. Jarchum, M. Equinda, L. Lipuma, A. Gobourne, A. Viale, C. Ubeda-Morant, J. Xavier, and E.G. Pamer, 2011. Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Infect. Immun. 80:62-73.)