The Evolution and Medicine Review

…bridging the gap.

Category: Infection (Page 1 of 5)

Malaria-Specific Antibody Diversification via Interchromosomal Insertion of a Non-Immunoglobulin Gene Sequence

Identifying broadly neutralizing antibodies against infectious agents such as influenza A viruses, HIV, and Plasmodium falciparum that display impressive degrees of antigenic variation is a major focus of investigators developing therapeutics and vaccines for pathogens of importance in public health (Corti and Lanzavecchia, 2013).  In a previous post, I discussed one study (Klein et al., 2013) illustrating the sorts of unanticipated types of mutations found for broadly neutralizing antibodies against HIV.  Lanzavecchia and colleagues have now identified antibodies reactive with antigens encoded by different isolates of Plasmodium falciparum and expressed on infected erythrocytes (Nature, 2015).  They find an unexpected source for the heavy chain variable domain amino acid sequences that confer the broad anti-malarial reactivity against proteins in the RIFIN family.

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Towards Xenografts in Clinical Transplantation: Multiplexed Negative Selection of Porcine Endogenous Retroviruses with CRISPR-Cas9

Clinical organ transplantation is now a large medical enterprise, with more than 29,000 organ transplants performed in 2014 in the United States alone (https://www.unos.org/data/transplant-trends/#transplants_by_organ_type+year+2014). Nevertheless, the number of organ donors is insufficient to meet the demand for new organs. For example, in the U.S. during 2014, there were 17,104 kidney transplants but 101,035 individuals on the waiting list for such transplants. Therefore, a recent study in Science (Yang et al., 2015) offers an important proof of principle for a necessary but not necessarily sufficient step on the path to safely using pig organs to substitute for failing human organs.

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Nietzsche Undone: An Infection that Doesn’t Kill You Can Make You Weaker

The German philosopher, Friedrich Nietzsche, is known for a number of ideas among which a particularly oft-quoted one is, “That which does not kill us makes us stronger” (https://www.goodreads.com/quotes/30-that-which-does-not-kill-us-makes-us-stronger). A recent report in Cell (Fonseca et al., 2015) offers evidence that in the context of infection and immunity, the above aphorism may not be a reliable guide to reality.

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Microbial Warfare and the Ecological Dynamics of Cystic Fibrosis Lung Disease

In a previous EMR post from December 30 of 2014 (see link below), I discussed a study (Science, 2014) that offered evidence for reciprocal selection of host and pathogen iron-binding proteins arising out the competition for their shared ligand, which is critical to the metabolisms of both parties to the conflict. A recent paper (J. Bacteriol., 2015) by Filkins et al. demonstrates another sort of competition focused on the acquisition of iron that can affect human health. This conflict occurs between two species of bacterial pathogen associated with lung disease in cystic fibrosis (CF) patients.

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Fighting HIV Evolution with an Evolved Therapeutic Agent: Phase I Dose Escalation Clinical Trial of a Potent Broadly Neutralizing Human Antibody

In previous commentaries (https://evmedreview.com/?p=1863; https://evmedreview.com/?p=837; https://evmedreview.com/?p=385), I have discussed the critical role of extensive B-cell and immunoglobulin gene evolution in generating broadly neutralizing antibodies for HIV-1.  Of course, the unprecedented magnitude of antibody evolution necessary to achieve potent neutralization of a high percentage of HIV strains reflects the unprecedented evolutionary plasticity of HIV that originates in both high mutation and recombination rates for the HIV genome (Korber et al., 2001).  A new study by Caskey et al. (Nature, 2015) from the Nussenzweig Laboratory reports results for a first-in-human dose escalation phase I clinical trial of a human monoclonal antibody (mAb) specific for the HIV envelope (env) protein.

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Chromosomal Catastrophe (Chromothripsis) Causing Curative Clonal Conquest

Last month, Murphy and colleagues (Cell, 2015) published a fascinating report about a patient with an immunodeficiency syndrome that underwent spontaneous resolution.  The mechanism for this remarkable outcome points to the importance of somatic cell selection and evolution in the origins, pathogenesis, and most dramatically in this case, elimination of disease.

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Putting the Kill in “Shock and Kill”: Overcoming Evolutionary Obstacles to HIV Cure

According to estimates by the World Health Organization, in 2013 on the order of 35 million people were infected with HIV worldwide (http://www.who.int/gho/hiv/en/).  Globally, about 1.5 million people are believed to have died from AIDS-related diseases in that year.  Substantial, although perhaps not insurmountable, obstacles to the development of a highly effective vaccine for HIV-1 have increased interest in curative strategies.  A key challenge to cure strategies is that infected people harbor a latent reservoir of infected CD4+ memory T cells that do not express significant amounts of viral proteins.  The paucity of viral proteins in these cells makes it more difficult to identify infected cells and eradicate them.  A new study (Deng et al., 2015) in Nature from Robert Siliciano’s lab at Johns Hopkins identifies an additional difficulty faced by one of the currently popular approaches to curative therapy but also, more optimistically, suggests a way to overcome this challenge.

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Cellular ‘Gold’: Competition for Iron as the Cause of Reciprocal Positive Selection of Host and Pathogen Iron-Binding Proteins

Iron is a critical metal for essential cellular processes, such as respiration, in both human and microbial cells.  Thus, in the context of infection, iron is a high-value cellular commodity and an evolutionist might reasonably expect a metallic tug-of-war between host and pathogen iron-binding proteins or other iron-binding molecules (siderophores).  This speculation is impressively supported in a paper published this month (Barber and Elde, 2014).  These authors provide strong evidence for positive selection affecting several sites in host (transferrin, Tf) and pathogen (transferrin binding protein A) iron-binding proteins based on a combination of genetic, structural, and functional experimental methods.

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Eukaryotic Exploitation of Bacterial Anti-Microbial Genes via Trans-Kingdom Horizontal Gene Transfer

 

An article published online at the Nature web site on November 24 (Chou et al., 2014) presents a fascinating study of examples in which bacterial genes have found their way to a number of distinct eukaryotic lineages including ticks and mites, gastropod (e.g., snails and slugs) and bivalve mollusks (e.g. clams and oysters), and choanoflagellates (a subset of ptotozoans).  Type VI secretion amidase effector (Tae) molecules (encoded by tae genes) can kill rival bacteria by degrading their cells walls when delivered into those competing cells.  The eukaryotes cited above all have “domesticated amidase effectors” (dae) genes, all of which are extremely similar to one of the four extant bacterial tae genes.  Of the four tae genes found in bacterial species, three have been transferred to one or another eukaryotic genome.

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Evolution and the Ebola Epidemic. II.

After posting my last commentary on the ongoing Ebola outbreak in West Africa, I listened to the netcast, This Week in Virology (www.twiv.tv), for September 14, 2014.  TWiV sessions, hosted by Vincent Racaniello, a well-known virologist at Columbia University, are generally highly informative, typically offering thoughtful discussions about recently published studies pertaining to viruses or addressing broad areas of virus-related research.

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