Klebsiella and Providencia emerge as lone survivors following long-term starvation of oral microbiota

Abstract

Significance This study illustrates the dynamics of the oral microbiome during long-term starvation. After an initial ecological collapse, only three species were recoverable and displayed significant transcriptional activity: Klebsiella pneumoniae, Klebsiella oxytoca, and Providencia alcalifaciens. Klebsiella spp. are significant human pathogens and are frequently resistant to multiple classes of antibiotics. In addition to its status as a clinical scourge in its own right, K. pneumoniae has emerged as a chief facilitator in the transfer of drug resistance genes from the environment to pathogens. Hospital surfaces contaminated with oral fluids are well-documented sources of outbreaks of drug-resistant Enterobacteriaceae; therefore, the ability of Klebsiella to outcompete its neighbors during starvation and survive long-term in saliva is particularly noteworthy. It is well-understood that many bacteria have evolved to survive catastrophic events using a variety of mechanisms, which include expression of stress-response genes, quiescence, necrotrophy, and metabolic advantages obtained through mutation. However, the dynamics of individuals leveraging these abilities to gain a competitive advantage in an ecologically complex setting remain unstudied. In this study, we observed the saliva microbiome throughout the ecological perturbation of long-term starvation, allowing only the species best equipped to access and use the limited resources to survive. During the first several days, the community underwent a death phase that resulted in a ∼50–100-fold reduction in the number of viable cells. Interestingly, after this death phase, only three species, Klebsiella pneumoniae, Klebsiella oxytoca, and Providencia alcalifaciens, all members of the family Enterobacteriaceae, appeared to be transcriptionally active and recoverable. Klebsiella are significant human pathogens, frequently resistant to multiple antibiotics, and recently, ectopic colonization of the gut by oral Klebsiella was documented to induce dysbiosis and inflammation. MetaOmics analyses provided several leads for further investigation regarding the ecological success of the Enterobacteriaceae. The isolates accumulated single nucleotide polymorphisms in known growth advantage in stationary phase alleles and produced natural products closely resembling antimicrobial cyclic depsipeptides. The results presented in this study suggest that pathogenic Enterobacteriaceae persist much longer than their more benign neighbors in the salivary microbiome when faced with starvation. This is particularly significant, given that hospital surfaces contaminated with oral fluids, especially sinks and drains, are well-established sources of outbreaks of drug-resistant Enterobacteriaceae.