Metallic copper surfaces kill bacteria on contact

Feb 17 2011

Metallic copper surfaces kill microbes on contact, decimating their populations, according to a paper in the February 2011 issue of the journal Applied and Environmental Microbiology. They do so literally in minutes, by causing massive membrane damage after about a minute's exposure, says the study's corresponding author, Gregor Grass of the University of Nebraska, Lincoln. This is the first study to demonstrate this mechanism of bacteriocide.

"When microbes were exposed to copper surfaces, we observed contact killing to take place at the rate of tens to hundreds of millions of bacterial cells within minutes," says Grass. "This means that usually no live microorganisms can be recovered from copper surfaces after exposure."

Thus, such surfaces could provide a critical passive defense against pathogens in hospitals, where hospital-acquired infections are becoming increasingly common and costly, killing 50,000-100,000 Americans annually, and costing more than $8 billion, according to one estimate. Still, Grass cautions that "metallic copper surfaces will never be able to replace other hygiene-improving methods already in effect," although they "will certainly decrease the costs associated with hospital-acquired infections and curb human disease as well as save lives." However, he expects this strategy to be inexpensive, because "the effect does not wear off."

Critically, the researchers provide strong evidence that genotoxicity through mutations and DNA lesions is not a cause of dry copper's antimicrobial properties. This is important, because mutations can cause cancer in animals and humans, and the lack of such mutations in bacteria from copper means that copper does not endanger humans.

The relevant experiment was particularly interesting. The bacterium, Deinococcus radiodurans, is unusually resistant to radiation damage, as its DNA repair mechanisms are especially robust. The hypothesis: if metallic copper kills by causing DNA damage, D. radiodurans should be immune to copper. It is not.

It is important to note that only dry copper surfaces are amazingly lethal to bacteria. The difference between dry and wet surfaces, such as copper pipes, is that only dry surfaces are inhospitable environments for bacterial growth. Bacteria can easily grow and reproduce in wet environments, and in so doing, they can develop resistance to copper. Resistance has not been observed to develop on dry copper surfaces.

(C. Esp-rito Santo, E.W. Lam, C.G. Elowsky, D. Quaranta, D.W. Domaille, C.J. Chang, and G. Grass, 2011. Bacterial killing by dry metallic copper surfaces. Appl. Environ. Microbiol. 77: 794-802.)

The population and diversity of nitrogen-fixing bacteria in agricultural soils varies more according to what crop was previously farmed than with whether those soils are organically or conventionally farmed, according to a paper in the February 2011 issue of the journal Applied and Environmental Microbiology.

This study was conducted as part of the ongoing and long-standing Nafferton Factorial Systems Comparison study in Northumberland in northeast England, UK. The Nafferton study has conventional and organic plots side by side, enabling precise comparisons between the two methods.

In the study, the researchers analyzed soil samples from both sets of plots, once each in March, in June, after application of fertilizer (manure to organic plots, chemical fertilizer to conventional), and in September, following application of pest control measures.

"In general, you would expect organic fertilizers and pesticides to be less harmful than conventional ones," says first author Caroline H. Orr of Northumbria University, Newcastle-upon-Tyne, UK. "However, we found that conventional fertility management led to a more active nitrogen-fixing community in June, directly after fertilizers were applied. This is possibly due to the positive effect of phosphorus, which is applied as part of conventional fertility management."

However, in September, use of organic crop protection protocols led to more activity among the nitrogen fixing bacteria as compared to when conventional pesticides were used, says Orr, suggesting that "nitrogen-fixing bacteria are particularly sensitive to the toxic effects of chemical pesticides."

It turns out the prior crop had a major influence on nitrogen-fixing activity, says Orr. Beans, legumes, commonly used in organic rotations have symbiotic relationships with bacteria that fix nitrogen for them; hence, they deplete less nitrogen from the soil, and the higher concentration of nitrate and ammonium suppresses the population of free-living nitrogen fixers. Conversely, soil growing barley (or other non-leguminous crops) would be relatively depleted of nitrogen, and so nitrogen-fixing bacteria would thrive, says Orr, remaining in higher numbers the following year.

The researchers assayed the population density of nitrogen fixing bacteria by measuring the concentration of nifH, the most conserved of the genes involved in nitrogen fixation. They sampled the density of all bacteria via 16S ribosomal RNA. The ribosomes are the machinery that reads ribonucleic acid to manufacture proteins.

(C.H. Orr, A. James, C. Leifert, J.M. Cooper, and S.P. Cummings, 2011. Diversity and activity of free-living nitrogen-fixing bacteria and total bacteria in organic and conventionally managed soils. Appl. Environ. Microbiol. 77:911-919.)

Researchers have engineered mice that model the switch from fetal to adult hemoglobin, an important step towards curing genetic blood diseases such as sickle cell anemia and beta-thalassemia. The research is published in the February 2011 issue of the journal Molecular and Cellular Biology.

They also produced for the first time a mouse that synthesizes a distinct fetal-stage hemoglobin, which was necessary for modeling human hemoglobin disorders. These diseases manifest as misshapen hemoglobin, causing anemia, which can be severe, as well as other symptoms, which can range from minor to life-threatening. The cure would lie in causing the body to revert to use of fetal hemoglobin.

"The motivation for our research is to understand the basic mechanisms of gene regulation in order to cure human disease," says Thomas Ryan of the University of Alabama Birmingham, who led the research. "If we can figure out how to turn the fetal hemoglobin back on, or keep it from switching off, that would cure these diseases."

The new model "mimics precisely the timing in humans, completing the switch after birth," says Ryan. "The previous models didn't do that." In earlier models, researchers inserted transgenes, large chunks of DNA containing the relevant genes, randomly into the mouse chromosome. In the new model, the investigators removed the adult mouse globin genes, and inserted the human fetal and adult genes in their places.

The successful engineering of a mouse with a fetal-stage hemoglobin means that humanized mouse models with mutant human genes will not die in utero.

While the basic principals behind the research are simple, the details are complex. For example, Ryan and Sean C. McConnell, a doctoral student who is the paper's first author, had to deal with the fact that hemoglobin switching occurs twice in H. sapiens, from embryonic to fetal globin chains in early fetal life, and then to adult globin chains at birth, while wild type mice have a single switch from embryonic to adult chains early in fetal life. "Instead of the single hemoglobin switch that occurs in wild type mice, our humanized knock-in mice now have two hemoglobin switches, just like humans, from embryonic to fetal in early fetal life, and then fetal to adult at birth," says Ryan.

Hemoglobin switching is believed to have evolved to enable efficient transfer of oxygen from the mother's hemoglobin to the higher oxygen affinity fetal hemoglobin in the placenta during fetal life.

(S.C. McConnell, Y. Huo, S. Liu, and T.M. Ryan, 2011. Human globin knock-in mice complete fetal-to-adult hemoglobin switching in postnatal development. Mol. Cell. Biol. 31:876-883.)

A new study suggests that differences in the host's genetics can make a big difference in susceptibility bacterial infection. In a study in the February 2011 Infection and Immunity, Virginia L. Miller of the University of North Carolina, Chapel Hill, and her collaborators show that the virulence of a strain of Yersinia pestis, notable for causing bubonic plague, varies drastically among mice strains with different genetic backgrounds. These findings carry major implications for vaccine development, says Miller.

A number of earlier reports dating back 20 years had suggested that removing this bacterium's capsule--an envelope of a loose protein gel surrounding the bacterial cell-had no effect on its virulence. Then, Miller and her collaborators performed the same experiment, with opposite results.

Searching for an explanation for the conflicting results, the only difference in the experiments that Miller could find was in the strains of mice, and so it occurred to her that their susceptibilities might be different. Her team tested that hypothesis by infecting two different strains of mice with Y. pestis in which the capsule had been removed. In one strain, the bacteria were nearly normally virulent, while in the other, they were relatively impotent.

This research made sense of the earlier experiments, "while highlighting the importance that host genetics can play in the dance between host and pathogen, and how it can influence the phenotype of a potential virulence factor," says Miller.

Moreover, these findings "demonstrate for the first time that the capsule is a Y. pestis virulence factor in a mouse infection model," says James Bliska of Stony Brook University, New York. "It had already been shown that [the capsule] is important for flea transmission, and therefore it was clear why [the capsule] was conserved in Y. pestis."

The research is critical for the development of a vaccine against both bubonic and pneumonic plague, also caused by Y. pestis, because considerable effort has been invested in establishing Caf1, an antigen within the capsule, as a protective antigen in vaccines against plague. But all the papers showing that removing the capsule had no effect on virulence had gradually undermined the case for using the capsule antigen in a vaccine, when it had been a major target for vaccine development. But now, "This paper may revive hope that Caf1 in conjunction with other antigens would be a useful component of a multivalent vaccine," says Eric Krukonis of the University of Michigan, Ann Arbor.

Developing such vaccines is important because "Y. pestis is still a major threat to humans, due to endemic pockets of Y. pestis-infected animals and fleas and potential bioterrorism use," Miller and her collaborators note. "A greater understanding of the requirement of the capsule for Y. pestis to cause disease is required. It is particularly important to investigate if natural capsule mutants are able to cause disease and in what contexts, as the current vaccine potentially would not protect against these strains."

(E.H. Weening, J.S. Cathelyn, G. Kaufman, M.B. Lawrenz, P. Price, W.E. Goldman, and V.L. Miller, 2011. The dependence of the Yersinia pestis capsule on pathogenesis is influenced by the mouse background. Infect. Immun. 79: 644-652.)

Source: American Society for Microbiology