Dataset Information

Disentangling bacterial invasiveness from lethality in an experimental host-pathogen system.

ABSTRACT: Quantifying virulence remains a central problem in human health, pest control, disease ecology, and evolutionary biology. Bacterial virulence is typically quantified by the LT50 (i.e., the time taken to kill 50% of infected hosts); however, such an indicator cannot account for the full complexity of the infection process, such as distinguishing between the pathogen's ability to colonize versus kill the hosts. Indeed, the pathogen needs to breach the primary defenses in order to colonize, find a suitable environment to replicate, and finally express the virulence factors that cause disease. Here, we show that two virulence attributes, namely pathogen lethality and invasiveness, can be disentangled from the survival curves of a laboratory population of Caenorhabditis elegans nematodes exposed to three bacterial pathogens: Pseudomonas aeruginosa, Serratia marcescens, and Salmonella enterica We first show that the host population eventually experiences a constant mortality rate, which quantifies the lethality of the pathogen. We then show that the time necessary to reach this constant mortality rate regime depends on the pathogen growth rate and colonization rate, and thus determines the pathogen invasiveness. Our framework reveals that Serratia marcescens is particularly good at the initial colonization of the host, whereas Salmonella enterica is a poor colonizer yet just as lethal once established. Pseudomonas aeruginosa, on the other hand, is both a good colonizer and highly lethal after becoming established. The ability to quantitatively characterize the ability of different pathogens to perform each of these steps has implications for treatment and prevention of disease and for the evolution and ecology of pathogens.

SUBMITTER: Biancalani T

PROVIDER: S-EPMC6558951 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:CONSPECTUS: The human innate immune system has evolved the means to reduce the bioavailability of first-row late d-block transition metal ions to invading microbial pathogens in a process termed "nutritional immunity". Transition metals from Mn(II) to Zn(II) function as metalloenzyme cofactors in all living cells, and the successful pathogen is capable of mounting an adaptive response to mitigate the effects of host control of transition metal bioavailability. Emerging evidence suggests that Mn, Fe, and Zn are withheld from the pathogen in classically defined nutritional immunity, while Cu is used to kill invading microorganisms. This Account summarizes new molecular-level insights into copper trafficking across cell membranes from studies of a number of important bacterial pathogens and model organisms, including Escherichia coli, Salmonella species, Mycobacterium tuberculosis, and Streptococcus pneumoniae, to illustrate general principles of cellular copper resistance. Recent highlights of copper chemistry at the host-microbial pathogen interface include the first high resolution structures and functional characterization of a Cu(I)-effluxing P1B-ATPase, a new class of bacterial copper chaperone, a fungal Cu-only superoxide dismutase SOD5, and the discovery of a small molecule Cu-bound SOD mimetic. Successful harnessing by the pathogen of host-derived bactericidal Cu to reduce the bacterial load of reactive oxygen species (ROS) is an emerging theme; in addition, recent studies continue to emphasize the importance of short lifetime protein-protein interactions that orchestrate the channeling of Cu(I) from donor to target without dissociation into bulk solution; this, in turn, mitigates the off-pathway effects of Cu(I) toxicity in both the periplasm in Gram negative organisms and in the bacterial cytoplasm. It is unclear as yet, outside of the photosynthetic bacteria, whether Cu(I) is trafficked to other cellular destinations, for example, to cuproenzymes or other intracellular storage sites, or the general degree to which copper chaperones vs copper efflux transporters are essential for bacterial pathogenesis in the vertebrate host. Future studies will be directed toward the identification and structural characterization of other cellular targets of Cu(I) trafficking and resistance, the physical and mechanistic characterization of Cu(I)-transfer intermediates, and elucidation of the mutual dependence of Cu(I) trafficking and cellular redox status on thiol chemistry in the cytoplasm. Crippling bacterial control of Cu(I) sensing, trafficking, and efflux may represent a viable strategy for the development of new antibiotics.

Project description:Identification of mechanisms that allow some species to outcompete others is a fundamental goal in ecology and invasive species management. One useful approach is to examine congeners varying in invasiveness in a comparative framework across native and invaded ranges. Acacia species have been widely introduced outside their native range of Australia, and a subset of these species have become invasive in multiple parts of the world. Within specific regions, the invasive status of these species varies. Our study examined whether a key mechanism in the life history of Acacia species, the legume-rhizobia symbiosis, influences acacia invasiveness on a regional scale. To assess the extent to which species varying in invasiveness correspondingly differ with regard to the diversity of rhizobia they associate with, we grew seven Acacia species ranging in invasiveness in California in multiple soils from both their native (Australia) and introduced (California) ranges. In particular, the aim was to determine whether more invasive species formed symbioses with a wider diversity of rhizobial strains (i.e. are more promiscuous hosts). We measured and compared plant performance, including aboveground biomass, survival, and nodulation response, as well as rhizobial community composition and richness. Host promiscuity did not differ among invasiveness categories. Acacia species that varied in invasiveness differed in aboveground biomass for only one soil and did not differ in survival or nodulation within individual soils. In addition, acacias did not differ in rhizobial richness among invasiveness categories. However, nodulation differed between regions and was generally higher in the native than introduced range. Our results suggest that all Acacia species introduced to California are promiscuous hosts and that host promiscuity per se does not explain the observed differences in invasiveness within this region. Our study also highlights the utility of assessing potential mechanisms of invasion in species' native and introduced ranges.

Dataset Information

Disentangling bacterial invasiveness from lethality in an experimental host-pathogen system.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets