Research

Myxococcus xanthus and antibiotics

Antibiotic Resistance is on the rise

According to the Centers for Disease Control (CDC), each year in the US, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections.

The Food and Drug Administration (FDA) estimates that 20% of infections in US hospitals involve multidrug-resistant bacteria.

Why?

1. Over-prescription of antibiotics/not taking the full prescription

The CDC estimates that 50% of antibiotics are incorrectly prescribed

2. Decrease in the number of new antibiotics being discovered

Since resistance is inevitable, antibiotics are a less profitable avenue of investigation for drug companies

What to do about the rise of antibiotic resistance?

First, we must curtail inappropriate use of  our current antibiotics

Second, continue the search for new antibiotics

My research focuses on finding new antibiotics in the genomes of bacteria that are unculturable in a labpratory setting


Heterologous Expression of novel antibiotics using a lab-friendly host

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Heterologous Expression - the expression of a gene (or gene cluster) by an organism that does not naturally possess the gene

By cutting DNA out of uncultivable bacteria, I am able to avoid having to find a way to culture each separate species and instead can focus on gene clusters of interest.


Evolving resistance to known antibiotics

In engineering M. xanthus to express novel antibiotics, I run the risk of M. xanthus being killed by the product. 

I am working to evolve M. xanthus to be resistant to antibiotics in different known classes. 

Increased antibiotic resistance may increase antibiotic expression, even if M. xanthus has not developed resistance to the specific antibiotic it is attempting to express.

Our current antibiotic supply operates along several different modes of action, with the vast majority of antibiotics interfering with either cell wall synthesis or protein synthesis.

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Evidence suggests that once bacteria have acquired resistance to an antibiotic that operates along one mode of action, it is easier to develop resistance to antibiotics that operate in the same manor.

EX: Resistance to tetracycline happens more quickly when the species is already resistant to kanamycin (both attack the 30S ribosomal subunit).

So, even if I am trying to use M. xanthus to express a novel antibiotic, if it operates along a mode of action that we have already documented there is a good chance that M. xanthus' initial resistance to the new antibiotic will be higher.

By increasing M. xanthus’ library of resistance I am increasing the chances that it will express as yet undocumented antibiotic gene clusters.

This whole process can be completed in less than 100 generations.