An Interlude on Pathogen Genomes

Brad jumps in amongst the Survey of Genomes to speak to the question of “why do we need to sequence the genome of a pathogen we just want to kill?”

Hey, Brad Goodner here.  It has been several episodes since I last got the chance to talk with you.  I hope you are enjoying the Survey of Genomes episodes guest hosted by students from my 2019 Hiram College Genetics course.  There are more of those episodes to come, but I wanted to jump in and provide some context.  So far, 4 out of the 7 student-hosted episodes have dealt with human pathogens.  Why sequence their genomes?  Don’t we just want to kill pathogens in order to cure infectious disease?

No doubt about it, healthcare practitioners not only want to diagnose infectious disease but also to treat it in such a way that the pathogen is no longer hurting the patient.  Over the past 70+ years, treatment for most non-viral infectious diseases has included the use of antimicrobial compounds like penicillin.  Each antimicrobial compound has a specific target, usually an enzyme or other larger macromolecule whose action is essential to the life of the pathogen.  In a perfect world, the antimicrobial compound will kill or inhibit the growth of the pathogen without impacting the patient.  However, the closer the evolutionary relationship of the pathogen to its host, the harder it is to find a pathogen-specific target.  For example, it is much harder to kill a worm infection than to kill a bacterial infection.  Sequencing the genome of a particular pathogen can show us how similar pathogen target macromolecules are to those in potential patients.  If there is sufficient difference, we have more options for how to stop the pathogen.  A genome sequence also illuminates the mechanisms by which the pathogen may resist particular antimicrobial compounds and a genome sequence may allow us to find potential new antimicrobial targets that are unique to a particular pathogen.

While antimicrobials have greatly improved human health, they are not foolproof.  The evolution of resistance in many pathogens has made it much harder to control certain infections.  However, if we understand how pathogens cause disease then maybe we can stop them from hurting us without having to kill them.  This relatively new idea is called the anti-infective strategy and it may allow us to control infections without the worry of selection for resistance in the pathogen.  A genome sequence of a pathogen compared to a closely related nonpathogen can help us better understand how that particular pathogen interacts with a potential host and how it might take advantage of the host and cause disease symptoms.  This knowledge may give us new options for blocking attachment of pathogen cells to our cells or for blocking one of its mechanisms for manipulating our cells for its own advantage.

Finally, better understanding how particular pathogens take advantage of a host and cause disease symptoms can provide us with pathogen-based tools that might have a future positive medical use under the right conditions.  For example, you have probably seen TV commercials for BoTox as a treatment for chronic migraines or to decrease frown lines or crow’s feet on one’s face.  BoTox is a medical treatment involving a known bacterial toxin called botulinum toxin A.  This toxin targets neuromuscular junctions and causes muscle paralysis in the relaxed state, also called flaccid paralysis.  Too much of this toxin through botulism food poisoning and muscles all over the body stop working.  This can lead to a risk of death due to impairment of breathing or other critical muscle-related functions.  However, very tiny amounts of this toxin when applied to very specific muscles in the face or scalp can relax those muscles for long periods of time providing relief from problems due to uncontrollable muscle contractions.  There are several other microbial toxins that have been turned into medicines or research tools.

There is an old saying that you should keep your friends close but your enemies even closer.  That can also apply to a pathogen through the use of its genome sequence.  Thanks for listening. Now lets get back to our survey of genomes and see how other life forms on Earth make a living.  See you next time.