Enterobacteriaceae Use Metabolic Flexibility to Survive 100 Days of Starvation

A new study may help to explain how bacteria present at low levels in healthy human mouths can persist for months and cause hospital outbreaks of drug-resistant infections.

Two bacteria typically found in the oral microbiome survived long-term starvation outside of the mouth in a new study, including bacteria from a family responsible for drug-resistant hospital infections. The findings may help scientists understand how some bacteria have evolved to survive catastrophic events.

For the new study, published in the in the Proceedings of the National Academy of Sciences journal, investigators from the Forsyth Institute, J. Craig Venter Institute, University of Washington, and University of California, Los Angeles, examined the microbiome of human saliva to examine how some bacteria have developed diverse strategies to survive adverse environmental events, such as starvation, oxidative stress, antimicrobials, and changes in pH and temperature.

The research team isolated hundreds of saliva-derived bacterial samples and placed them in test tubes, starving them for more than 100 days. Although most bacterial species died in the first few days, at the end of the study only 3 species from the Enterobacteriaceae family—Klebsiella pneumoniae, Klebsiella oxytoca, and Providencia alcalifaciens—had survived the death phase. The finding is notable, as some Enterobacteriaceae are antibiotic-resistant and are known to transfer drug resistance genes from the environment to pathogens, in addition to being responsible for health care-associated infections.

In an interview with Contagion®, study co-author Wenyuan Shi, PhD, explained the clinical significance of the study’s findings. “The new microbiome research is providing so much new information that we were not aware of before,” Shi said. The paper notes that although Klebsiella are not dominant and accounted for only about 0.1% of all microbes in the oral environment, the bacterial species survived conditions outside of the mouth that killed off more abundant bacteria. “In this case, a nasty pathogen is hiding among normal oral microbial flora and becoming dominant under certain conditions. Thus, understanding the oral microbiome and maintaining good oral health has a new meaning.”

The survival of Enterobacteriaceae species kept in long-term starvation may be due to the fact that they have larger genomes than other oral bacteria which give them the “metabolic flexibility” to access more diverse energy sources, according to the study investigators. Genetic mutations in Klebsiella, for example, may allow the species to survive starvation, which may be why Klebsiella persists in health care settings, such as on hospital sinks or equipment.

“A lot of current sterilization procedures just kill bacteria, do not remove their dead bodies,” Shi explained. “This study suggests that some pathogens have strong survival skills and can live on the dead bodies of other bacteria, giving a new level of concern that we need not only do sterilization to kill the bacteria, but also wash the equipment clean to remove the dead bacteria bodies.”

The investigators say that the mechanisms used by these Enterobacteriaceae to outlast their microbial neighbors during long-term starvation require further investigation. To that end, Shi notes that the team plans to explore how Klebsiella got established in the human oral cavity and how to get rid of them before they cause any problem.