Competitiveness for Nodule Colonization in Sinorhizobium meliloti: Combined In Vitro -Tagged Strain Competition and Genome-Wide Association Analysis

Decoding the competitive pattern that occurs in the rhizosphere is challenging in the study of bacterial social interaction strategies. To date, the single-gene approach has mainly been used to uncover the bases of nodulation, but there is still a knowledge gap regarding the main features that a priori characterize rhizobial strains able to outcompete indigenous rhizobia.

Defining the root cause of reduced H1N1 live attenuated influenza vaccine effectiveness: low viral fitness leads to inter-strain competition

In the 2013–14 and 2015–16 influenza seasons, reduced vaccine effectiveness (VE) was observed for the H1N1 component of the FluMist quadrivalent live attenuated influenza vaccine (QLAIV) in the USA, leading to loss of Advisory Committee on Immunization Practices recommendation. Here we demonstrate in ferrets that 2015–16A/H1N1pdm09 vaccine strain A/Bolivia/559/2013 (A/BOL13) is outcompeted in trivalent (TLAIV) and QLAIV formulations, leading to reduced protection from wild-type challenge. While monovalent (MLAIV) A/BOL13 provided significant protection from wild-type virus shedding and fever at doses as low as 3.0 log10 fluorescent focus units (FFU), it failed to provide a similar level of protection in TLAIV or QLAIV formulation, even at a 6.0 log10 FFU dose. Conversely, clinically effective H1N1 strain A/New Caledonia/20/1999 provided significant protection in MLAIV, TLAIV, and QLAIV formulations. In conclusion, reduced A/BOL13 replicative fitness rendered it susceptible to inter-strain competition in QLAIV, contributing to its reduced VE in the 2015–16 season.

Experimental evaluation of ecological principles to understand and modulate the outcome of bacterial strain competition in gut microbiomes

It is unclear if coexistence theory can be applied to gut microbiomes to understand their characteristics and modulate their composition. Through strictly controlled colonization experiments in mice, we demonstrated that strains of Akkermansia muciniphila and Bacteroides vulgatus could only be established if microbiomes were devoid of exactly these species. Strains of A. muciniphila showed strict competitive exclusion, while B. vulgates strains coexistedbut populations were still influenced by competitive interactions. Priority effects were detected for both species as strains’ competitive fitness increased when colonizing first. Based on these observations, we devised a subtractive strategy for A. muciniphila using antibiotics and demonstrated that a strain from an assembled community can be stably replaced by another strain. Altogether, these results suggest that aspects of coexistence theory, e.g., niche partitioning and the impact of priority effects on fitness differences, can be applied to explain ecological characteristics of gut microbiomes and modulate their composition.

Competition delays multi-drug resistance evolution during combination therapy

ABSTRACTCombination therapies have shown remarkable success in preventing the evolution of resistance to multiple drugs, including HIV, tuberculosis, and cancer. Nevertheless, the rise in drug resistance still remains an important challenge. The capability to accurately predict the emergence of resistance, either to one or multiple drugs, may help to improve treatment options. Existing theoretical approaches often focus on exponential growth laws, which may not be realistic when scarce resources and competition limit growth. In this work, we study the emergence of single and double drug resistance in a model of combination therapy of two drugs. The model describes a sensitive strain, two types of single-resistant strains, and a double-resistant strain. We compare the probability that resistance emerges for three growth laws: exponential growth, logistic growth without competition between strains, and logistic growth with competition between strains. Using mathematical estimates and numerical simulations, we show that between-strain competition only affects the emergence of single resistance when resources are scarce. In contrast, the probability of double resistance is affected by between-strain competition over a wider space of resource availability. This indicates that competition between different resistant strains may be pertinent to identifying strategies for suppressing drug resistance, and that exponential models may overestimate the emergence of resistance to multiple drugs. A by-product of our work is an efficient strategy to evaluate probabilities of single and double resistance in models with multiple sequential mutations. This may be useful for a range of other problems in which the probability of resistance is of interest.

Spatial structure affects phage efficacy in infecting dual-strain biofilms of Pseudomonas aeruginosa

Bacterial viruses, or phage, are key members of natural microbial communities. Yet much research on bacterial-phage interactions has been conducted in liquid cultures involving single bacterial strains. Here we explored how bacterial diversity affects the success of lytic phage in structured communities. We infected a sensitive Pseudomonas aeruginosa strain PAO1 with a lytic phage Pseudomonas 352 in the presence versus absence of an insensitive P. aeruginosa strain PA14, in liquid culture versus colonies on agar. We found that both in liquid and in colonies, inter-strain competition reduced resistance evolution in the susceptible strain and decreased phage population size. However, while all sensitive bacteria died in liquid, bacteria in colonies could remain sensitive yet escape phage infection, due mainly to reduced growth in colony centers. In sum, spatial structure can protect bacteria against phage infection, while the presence of competing strains reduces the evolution of resistance to phage.

Co-occurring soil bacteria exhibit a robust competitive hierarchy and lack of non-transitive interactions

Microbial communities are typically incredibly diverse, and this diversity is thought to play a key role in community function. However, explaining how this diversity can be maintained is a major challenge in ecology. Temporal fluctuations and spatial structure in the environment likely play a key role, but it has also been suggested that the structure of interactions within the community may act as a stabilizing force for species diversity. In particular, if competitive interactions are non-transitive as in the classic rock-paper-scissors game, they can contribute to the maintenance of species diversity; on the other hand, if they are predominantly hierarchical, any observed diversity must be maintained via other mechanisms. Here, we investigate the network of pairwise competitive interactions in a model community consisting of 20 strains of naturally co-occurring soil bacteria. We find that the interaction network is strongly hierarchical and lacks significant non-transitive motifs, a result that is robust across multiple environments. Moreover, in agreement with recently proposed community assembly rules, the full 20-strain competition resulted in extinction of all but three of the most highly competitive strains, indicating that higher order interactions do not play a major role in structuring this community. The lack of non-transitivity and higher order interactions in vitro indicates that other factors, such as temporal or spatial heterogeneity, must be at play in enabling these strains to coexist in nature.