Bacterial defences: mechanisms, evolution and antimicrobial resistance

Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution

Universality in Bacterial Colonies

The emergent spatial patterns generated by growing bacterial colonies have been the focus of intense study in physics during the last twenty years. Both experimental and theoretical investigations have made possible a clear qualitative picture of the different structures that such colonies can exhibit, depending on the medium on which they are growing. However, there are relatively few quantitative descriptions of these patterns. In this paper, we use a mechanistically detailed simulation framework to measure the scaling exponents associated with the advancing fronts of bacterial colonies on hard agar substrata, aiming to discern the universality class to which the system belongs. We show that the universal behavior exhibited by the colonies can be much richer than previously reported, and we propose the possibility of up to four different sub-phases within the medium-to-high nutrient concentration regime. We hypothesize that the quenched disorder that characterizes one of these sub-phases is an emergent property of the growth and division of bacteria competing for limited space and nutrients.Comment: 12 pages, 5 figure

Emergence of Spatial Structure in Cell Groups and the Evolution of Cooperation

On its own, a single cell cannot exert more than a microscopic influence on its immediate surroundings. However, via strength in numbers and the expression of cooperative phenotypes, such cells can enormously impact their environments. Simple cooperative phenotypes appear to abound in the microbial world, but explaining their evolution is challenging because they are often subject to exploitation by rapidly growing, non-cooperative cell lines. Population spatial structure may be critical for this problem because it influences the extent of interaction between cooperative and non-cooperative individuals. It is difficult for cooperative cells to succeed in competition if they become mixed with non-cooperative cells, which can exploit the public good without themselves paying a cost. However, if cooperative cells are segregated in space and preferentially interact with each other, they may prevail. Here we use a multi-agent computational model to study the origin of spatial structure within growing cell groups. Our simulations reveal that the spatial distribution of genetic lineages within these groups is linked to a small number of physical and biological parameters, including cell growth rate, nutrient availability, and nutrient diffusivity. Realistic changes in these parameters qualitatively alter the emergent structure of cell groups, and thereby determine whether cells with cooperative phenotypes can locally and globally outcompete exploitative cells. We argue that cooperative and exploitative cell lineages will spontaneously segregate in space under a wide range of conditions and, therefore, that cellular cooperation may evolve more readily than naively expected

Growth dynamics and the evolution of cooperation in microbial populations

Microbes providing public goods are widespread in nature despite running the risk of being exploited by free-riders. However, the precise ecological factors supporting cooperation are still puzzling. Following recent experiments, we consider the role of population growth and the repetitive fragmentation of populations into new colonies mimicking simple microbial life-cycles. Individual-based modeling reveals that demographic fluctuations, which lead to a large variance in the composition of colonies, promote cooperation. Biased by population dynamics these fluctuations result in two qualitatively distinct regimes of robust cooperation under repetitive fragmentation into groups. First, if the level of cooperation exceeds a threshold, cooperators will take over the whole population. Second, cooperators can also emerge from a single mutant leading to a robust coexistence between cooperators and free-riders. We find frequency and size of population bottlenecks, and growth dynamics to be the major ecological factors determining the regimes and thereby the evolutionary pathway towards cooperation.Comment: 26 pages, 6 figure

Cooperative secretions facilitate host range expansion in bacteria

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses

Combinatorial quorum sensing allows bacteria to resolve their social and physical environment

Quorum sensing (QS) is a cell–cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. Although the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here, we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of, and response to, complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (nonadditive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa and demonstrate significant differences in signal decay betweeallyn its two primary signal molecules, as well as diverse combinatorial responses to dual-signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic “AND-gate” responses to multiple signal inputs, ensuring the effective expression of secreted factors in high-density and low mass-transfer environments. Our results support a new functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication

Population Dynamics Constrain the Cooperative Evolution of Cross-Feeding

Cross-feeding is the exchange of nutrients among species of microbes. It has two potential evolutionary origins, one as an exchange of metabolic wastes or byproducts among species, the other as a form of cooperation known as reciprocal altruism. This paper explores the conditions favoring the origin of cooperative cross-feeding between two species. There is an extensive literature on the evolution of cooperation, and some of the requirements for the evolution of cooperative cross-feeding follow from this prior work–specifically the requirement that interactions be limited to small groups of individuals, such as colonies in a spatially structured environment. Evolution of cooperative cross-feeding by a species also requires that cross-feeding from the partner species already exists, so that the cooperating mutant will automatically be reciprocated for its actions. Beyond these considerations, some unintuitive dynamical constraints apply. In particular, the benefit of cooperative cross-feeding applies only in the range of intermediate cell densities. At low density, resource concentrations are too low to offset the cost of cooperation. At high density, resources shared by both species become limiting, and the two species become competitors. These considerations suggest that the evolution of cooperative cross-feeding in nature may be more challenging than for other types of cooperation. However, the principles identified here may enable the experimental evolution of cross-feeding, as born out by a recent study

Resource limitation drives spatial organization in microbial groups.

Dense microbial groups such as bacterial biofilms commonly contain a diversity of cell types that define their functioning. However, we have a limited understanding of what maintains, or purges, this diversity. Theory suggests that resource levels are key to understanding diversity and the spatial arrangement of genotypes in microbial groups, but we need empirical tests. Here we use theory and experiments to study the effects of nutrient level on spatio-genetic structuring and diversity in bacterial colonies. Well-fed colonies maintain larger well-mixed areas, but they also expand more rapidly compared with poorly-fed ones. Given enough space to expand, therefore, well-fed colonies lose diversity and separate in space over a similar timescale to poorly fed ones. In sum, as long as there is some degree of nutrient limitation, we observe the emergence of structured communities. We conclude that resource-driven structuring is central to understanding both pattern and process in diverse microbial communities

Co-Swarming and Local Collapse: Quorum Sensing Conveys Resilience to Bacterial Communities by Localizing Cheater Mutants in Pseudomonas aeruginosa

Background: Members of swarming bacterial consortia compete for nutrients but also use a co-operation mechanism called quorum sensing (QS) that relies on chemical signals as well as other secreted products (‘‘public goods’’) necessary for swarming. Deleting various genes of this machinery leads to cheater mutants impaired in various aspects of swarming cooperation. Methodology/Principal Findings: Pairwise consortia made of Pseudomonas aeruginosa, its QS mutants as well as B. cepacia cells show that a interspecies consortium can ‘‘combine the skills’ ’ of its participants so that the strains can cross together barriers that they could not cross alone. In contrast, deleterious mutants are excluded from consortia either by competition or by local population collapse. According to modeling, both scenarios are the consequence of the QS signalling mechanism itself. Conclusion/Significance: The results indirectly explain why it is an advantage for bacteria to maintain QS systems that can cross-talk among different species, and conversely, why certain QS mutants which can be abundant in isolated niches