Wednesday, February 14, 2018

Infections Develop Via a Sequence of Biological Steps

A prior post listed 7 assertions regarding the role of infectious organisms on the human genome. In the next few blogs we'll look at each assertion, in excerpts from Precision Medicine and the Reinvention of Human Disease. Here's the seventh:

By dissecting the biological steps involved in the pathogenesis of infectious disease, it is possible to develop new treatments, other than antibiotics, that will be effective against a range of related organisms.

Nature, by interfering with the different steps in the development of infectious diseases, has a variety of protective mechanisms against organisms. For example, to defend against malaria, nature has preserved various mutations that render red cells unsuitable hosts for malarial guests. For example, individuals with hemoglobin variants HbS (sickle cell trait), HbC, and HbE increase the likelihood that an infected red cell will lyse. Likewise, but for obscure reasons, regulatory defects in hemoglobin synthesis, as seen in thalassemia, may also confer some protection against malaria. Also, variations in a structural protein of erythrocytes, SLC4A1, causing ovalocytosis; and polymorphisms of the glucose-6-phosphate dehydrogenase gene [57] both seem to protect against malaria.

We see individuals resistant to malaria due to absence of the Duffy protein required for Plasmodium vivax to bind and enter erythrocytes [58]. Knowing this, the Duffy-binding protein in the malaria parasite is now being studied as a potential drug or vaccine target as a new strategy against malaria [58]. More generally, drugs known as entry inhibitors are being developed based on knowledge that the attachment and entry of organisms may depend upon specific cooperative pathways, in host and invader cells, that can be targeted by drugs. We know that there are many steps in the infection process that could be blocked by small changes in proteins that are unrelated to the immune process. For example, for an infectious agent to invade and flourish in an organism, it must gain entry into the tissues of the body, evading physical and chemical defenses along its way. It must find a place in which it can receive nourishment appropriate to its species and avoid any toxins that may be produced by its host. It must be able to grow as a collection of organisms, and this typically means that the host must permit some degree of invasion through its own tissues. These are just a few of the nonimmunological hurdles that invasive organisms must jump over, if they are to infect an organism. Every step in the pathogenesis of infectious disease provides another therapeutic opportunity. As we learn more about the pathways of development of infectious diseases that have become increasingly resistant to antibiotics, we will come to rely on Precision Medicine to prevent, diagnose, and treat infections.

- Jules Berman

key words: precision medicine, infections disease, biological steps, pathogenesis, jules j berman Ph.D., M.D.

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