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Scientists have unveiled details of how a unique microbe seeks and destroys a variety of plant and animal pathogens, findings that offer clues for new weapons against bacterial infections. By sequencing the entire genome of Bdellovibrio bacteriovorus and analyzing its life cycle, researchers in Germany are now able to describe the molecular mechanisms used by these predatory bacteria, including those involving many novel antimicrobial enzymes (Science. 2004;303:689-692). The authors suggest their findings could be used to design new antibiotics. "We are trying to identify those enzymes that have lytic or antimicrobial capabilities. We believe this is in the range of about 250. And they could be used either by themselves or as a cocktail to contain certain bacterial infections," said principal investigator Stephan Schuster, PhD, of the Max-Planck-Institute for Developmental Biology, in Tübingen. The wide variety of B bacteriovorus lytic enzymes that Schuster and colleagues identified can degrade complex molecules such as proteins, carbohydrates, DNA, and RNA. The bacteria might also be used intact, as a type of living antibiotic. Mode of attack Mode of attack Bdellovibrio's name comes from the Latin bdella, meaning "leechlike," and vibrio, meaning "curved bacteria." The bacteria can be found in fresh and marine waters, as well as in soil and sewage. Mode of attack Schuster and colleagues outlined the steps that B bacteriovorus takes when attacking other Gram-negative bacteria—including those that can cause human illness, such as Escherichia coli, Salmonella, and Pseudomonas. Once attached to its prey, the predator bores a hole in the cell wall, invades the cell, and degrades its internal components. Mode of attack Researchers are interested in understanding the details of B bacteriovorus' mode of attack to find components of the prey bacteria that are not targeted by conventional antibiotics. This information could help in the design of new antimicrobial agents to fight bacterial infections. Color-enhanced scanning electron micrographs show the life cycle of the predatory bacterium Bdellovibrio bacteriovorus (yellow). It moves towards, attaches to, and invades its prey (blue). Then, after pillaging its prey's cellular components for its own growth and reproduction, it lyses the host cell and begins the cycle anew. (Credit: Snježana Rendulić, Jürgen Berger, Stephan C. Schuster, PhD/Max-Planck-Institute) Mode of attack As B bacteriovorus chews up the cellular components of its prey, it plunders the organism's amino acids for its own livelihood. "One of the most striking findings we made is that Bdellovibrio is not capable of synthesizing all of its amino acids. And this means it can only reproduce and grow while it is in the host," said Schuster. After it feasts on its bacterial prey, B bacteriovorus reproduces and bursts free, in search of a new quarry. Mode of attack Schuster said that although there are two other bacterial predators in nature, they infect only environmental strains, such as photosynthetic bacteria in plants. B bacteriovorus is unique, said Schuster, because it not only preys on a lot of enterobacteria, the Gram-negative bacteria sometimes found in the intestines of mammals, but also on plant pathogens and pathogens other than enterobacteria that occur in animals and humans. This means that the tools the predatory bacterium uses to tackle such a wide-ranging menu may have broad applications in medicine and food safety. For example, B bacteriovorus, may provide tools to fight Salmonella contamination in meat or fish. Harmless to humans? Harmless to humans? Because B bacteriovorus is believed to be harmless to humans—it cannot invade mammalian cells—scientists suggest that the bacterium itself may be able to serve as a therapeutic agent, as a living antibiotic. In addition, laboratory experiments have turned up no evidence of gene transfer between B bacteriovorus and its prey, so that it is considered unlikely that the organism would acquire genes that would make it pathogenic to humans or other mammals. Harmless to humans? "A foreseeable application [of B bacteriovorus] is as a living antibiotic in patients—for example, in those cases where existing antibiotics no longer work," said Schuster. Harmless to humans? Such a living antibiotic could have a strategic advantage over conventional antimicrobial drugs. The researchers speculate that while genetic mutations enable bacterial pathogens to become resistant to antibiotics, a living antibiotic could theoretically similarly evolve through mutation to be able to keep the prey bacteria in check. Harmless to humans? Laboratory studies show that the cell surface of B bacteriovorus is only weakly immunogenic, in contrast to those of many other bacterial strains that provoke serious immune reactions (J Biol Chem. 2003;278:27502-27512). Nontheless, it's clear that introduction of foreign elements such as these into the body would have to be considered with all due concern about possible consequences. However, scientists are hopeful that B bacteriovorus may prove safe and effective in a number of clinical applications. Harmless to humans? "This is what we hope," said Schuster. "And since this paper came out, there are many people writing to me, and they come up with new applications that we haven't even thought about."
JAMA – American Medical Association
Published: Mar 10, 2004
Keywords: bacteria,eye,antimicrobials
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