- Email: [email protected]
Tenacity at the biological gym
Cross-talk
Tenacity at the biological gym Tenacity is less discussed nowadays as a cardinal requirement for success in research. There is now little space in the system for obsessive investigators to persist with avenues of enquiry that are overwhelmed by technical difficulties or road-blocked by dull grants committees. It is inconceivable, for example, that early 21st century researchers could show the dogged determination of Andrew Schally and Roger Guillemin, who took 20 years to characterise the hypothalamic releasing factors. As recounted by Nicholas Wade in The Nobel Duel (Anchor Press, 1981), Schally and Guillemin not only faced formidable challenges at the laboratory bench. They also had to contend with scepticism from distinguished peers over the very existence of the proteins they were pursuing. Although their battle culminated in a Nobel Prize in 1977, it was a monumental struggle. I’m not yet sure whether Michael Brown will become a Nobel laureate. However, his work and speculation over the past decade on protozoa as reservoirs for pathogens certainly has the hallmarks of dogged tenacity. Working at the University of Aston, he has come to believe that there are probably many more examples of this phenomenon than the residence of Legionella pneumophila inside amoebae. In Brown’s scenario, bacteria invade protozoa, replicate, and emerge better fitted to enter other protozoa, as well as more resistant to killers such as antibiotics and biocides. Intra-protozoal life both protects bacteria from adverse environmental conditions and also enhances their infectivity. By analogy, they use their hosts as “biological gymnasia” where they can “train” for encounters with more evolved mammalian cells. Protozoa may be sources of emerging pathogens, helping bacteria to move from the environment to human and other animal hosts. Mike Brown and his collaborators have fleshed out the theory with a string of publications, without necessarily convincing everyone of its wide-ranging implications. Recently, however, support has been coming from other independent investigators. One of the most recent additions is a paper by Selwa Alsam and colleagues at Birkbeck College, University of London, and Johns Hopkins University School of Medicine, Baltimore in the Journal of Medical Microbiology (2006; 55: 689). Their experimental subject is acanthamoeba, a free-living protozoon widely distributed in the soil and air, but also found in swimming pools and tap water. Familiar to contact lens wearers as a potential cause of keratitis, it is also now recognised as a host for several pathogens in addition to L pneumophila. These include Helicobacter pylori and Listeria monocotogenes.
http://infection.thelancet.com Vol 6 August 2006
Alsam and colleagues were intrigued by the general phenomenon of bacteria-amoebae interactions, and by observations that, while protozoa can play host to bacteria, on other occasions they are grazed upon and killed by bacteria. They were especially interested in interactions between an isolate of Acanthamoeba castellanii capable of causing keratitis and two versions of Escherichia coli—an invasive K1 strain recovered from a patient with meningitis, and the laboratory strain K12. They found several important differences. For example, K1 showed significantly greater association with the amoeba (in terms of both invasion and attachment) than K12. Once inside the cell, moreover, K1 remained viable and multiplied, whereas K12 was killed. There was a likely parallel here with human macrophages, recent studies having shown that K1, but not K12, can enter these cells, survive, and replicate. Alsam and colleagues’ tests with mutant organisms established that the outer membrane protein A and lipopolysaccharide were crucial for intracellular survival. “Overall, our findings suggest that the interactions of E coli and A castellanii are highly complex and depend on the virulence of E coli,” they write. “Acanthamoeba may act as a bacterial predator, or as a reservoir or ‘Trojan horse’ for bacteria, with environmental and clinical implications.” These experiments with a single system do not, of course, validate Mike Brown’s entire scenario. But together with other findings now emerging, they add to a mosaic of evidence to which grant-awarding bodies should pay more attention in future.
Bernard Dixon 130 Cornwall Road, Ruislip Manor, Middlesex HA4 6AW, UK; [email protected]
465
Tenacity at the biological gym Tenacity is less discussed nowadays as a cardinal requirement for success in research. There is now little space in the system for obsessive investigators to persist with avenues of enquiry that are overwhelmed by technical difficulties or road-blocked by dull grants committees. It is inconceivable, for example, that early 21st century researchers could show the dogged determination of Andrew Schally and Roger Guillemin, who took 20 years to characterise the hypothalamic releasing factors. As recounted by Nicholas Wade in The Nobel Duel (Anchor Press, 1981), Schally and Guillemin not only faced formidable challenges at the laboratory bench. They also had to contend with scepticism from distinguished peers over the very existence of the proteins they were pursuing. Although their battle culminated in a Nobel Prize in 1977, it was a monumental struggle. I’m not yet sure whether Michael Brown will become a Nobel laureate. However, his work and speculation over the past decade on protozoa as reservoirs for pathogens certainly has the hallmarks of dogged tenacity. Working at the University of Aston, he has come to believe that there are probably many more examples of this phenomenon than the residence of Legionella pneumophila inside amoebae. In Brown’s scenario, bacteria invade protozoa, replicate, and emerge better fitted to enter other protozoa, as well as more resistant to killers such as antibiotics and biocides. Intra-protozoal life both protects bacteria from adverse environmental conditions and also enhances their infectivity. By analogy, they use their hosts as “biological gymnasia” where they can “train” for encounters with more evolved mammalian cells. Protozoa may be sources of emerging pathogens, helping bacteria to move from the environment to human and other animal hosts. Mike Brown and his collaborators have fleshed out the theory with a string of publications, without necessarily convincing everyone of its wide-ranging implications. Recently, however, support has been coming from other independent investigators. One of the most recent additions is a paper by Selwa Alsam and colleagues at Birkbeck College, University of London, and Johns Hopkins University School of Medicine, Baltimore in the Journal of Medical Microbiology (2006; 55: 689). Their experimental subject is acanthamoeba, a free-living protozoon widely distributed in the soil and air, but also found in swimming pools and tap water. Familiar to contact lens wearers as a potential cause of keratitis, it is also now recognised as a host for several pathogens in addition to L pneumophila. These include Helicobacter pylori and Listeria monocotogenes.
http://infection.thelancet.com Vol 6 August 2006
Alsam and colleagues were intrigued by the general phenomenon of bacteria-amoebae interactions, and by observations that, while protozoa can play host to bacteria, on other occasions they are grazed upon and killed by bacteria. They were especially interested in interactions between an isolate of Acanthamoeba castellanii capable of causing keratitis and two versions of Escherichia coli—an invasive K1 strain recovered from a patient with meningitis, and the laboratory strain K12. They found several important differences. For example, K1 showed significantly greater association with the amoeba (in terms of both invasion and attachment) than K12. Once inside the cell, moreover, K1 remained viable and multiplied, whereas K12 was killed. There was a likely parallel here with human macrophages, recent studies having shown that K1, but not K12, can enter these cells, survive, and replicate. Alsam and colleagues’ tests with mutant organisms established that the outer membrane protein A and lipopolysaccharide were crucial for intracellular survival. “Overall, our findings suggest that the interactions of E coli and A castellanii are highly complex and depend on the virulence of E coli,” they write. “Acanthamoeba may act as a bacterial predator, or as a reservoir or ‘Trojan horse’ for bacteria, with environmental and clinical implications.” These experiments with a single system do not, of course, validate Mike Brown’s entire scenario. But together with other findings now emerging, they add to a mosaic of evidence to which grant-awarding bodies should pay more attention in future.
Bernard Dixon 130 Cornwall Road, Ruislip Manor, Middlesex HA4 6AW, UK; [email protected]
465