Pathogen Growth Rates in CF Sputum are Slow and Heterogeneous: Implications for Research and Treatment Strategies

Abstract

Conventionally, microorganisms are grown in the laboratory under conditions where doubling times are less than an hour. While it is well appreciated that microbes experience nutrient limitation in nature, we know very little about how quickly they are growing or what limits them in any particular environment. This is particularly true in chronic infections, yet our ignorance of these environments (and the ensuing physiological response of pathogens) is one of the main reasons current antibiotic treatments are not fully effective. In collaboration with clinicians at Children’s Hospital Los Angeles and geochemists and bioengineers at Caltech, we have been developing and applying new methods to better characterize the chemical and biological states that occur in CF sputum. Such information is necessary to design relevant laboratory experiments to elucidate pathogen survival strategies in vivo. I will discuss the implications our findings for treating CF infections.