The territorial nature of aggression in biofilms.

Microbial conflicts have a particularly aggressive nature. In addition to other chemical, mechanical, and biological weapons in their repertoire, bacteria have evolved bacteriocins, which are narrow-spectrum toxins that kill closely related strains. Bacterial cells are known to frequently use their arsenal while competing against each other for nutrients and space. This stands in contrast with the animal world, where conflicts over resources and mating opportunities are far less lethal, and get commonly resolved via ritualized fighting or "limited war" tactics. Prevalence of aggression in microbial communities is usually explained as due to their limited ability to resolve conflicts via signaling as well as their limited ability to pull out from conflicts due to the sessile nature of their life within biofilms. We use an approach that combines Evolutionary Game Theory (EGT) and Individual-based Modeling (IbM) to investigate the origins of aggression in microbial conflicts. In order to understand how the spatial mode of growth affects the cost of a fight, we compare the growth dynamics emerging from engaging in aggression in a well-mixed system to a spatially structured system. To this end, a mathematical model is constructed for the competition between two bacterial strains where each strain produces a diffusible toxin to which the other strain is sensitive. It is observed that in the biofilm growth mode, starting from a mixed layer of two strains, mutual aggression gives rise to an exceedingly high level of spatial segregation, which in turn reduces the cost of aggression on both strains compared to when the same competition occurs in a well-mixed culture. Another observation is that the transition from a mixed layer to segregated growth is characterized by a switch in the overall growth dynamics. An increased "lag time" is observed in the overall population growth curve that is associated with the earlier stages of growth, when each strain is still experiencing the inhibiting effect of the toxin produced by its competitor. Afterwards, an exponential phase of growth kicks in once the competing strains start segregating from each other. The emerging "lag time" arises from the spiteful interactions between the two strains rather than acclimation of cells' internal physiology. Our analysis highlights the territorial nature of microbial conflicts as the key driver to their elevated levels of aggression as it increases the benefit-to-cost ratio of participating in antagonistic interactions.

Dishonest Signaling in Microbial Conflicts.

Quorum sensing is a cell-cell communication system that bacteria use to express social phenotypes, such as the production of extracellular enzymes or toxins, at high cell densities when these phenotypes are most beneficial. However, many bacterial strains are known to lack a sensing mechanism for quorum signals, despite having the gene responsible for releasing the signals to the environment. The aim of this article is 2-fold. First, we utilize mathematical modeling and signaling theory to elucidate the advantage that a bacterial species can gain by releasing quorum signals, while not being able to sense them, in the context of ecological competition with a focal quorum sensing species, by reducing the focal species' ability to optimize the timing of expression of the quorum sensing regulated phenotype. Additionally, the consequences of such "dishonest signaling," signaling that has evolved to harm the signal's receiver, on the focal quorum sensing species are investigated. It is found that quorum sensing bacteria would have to incur an additional, strategic, signaling cost in order to not suffer a reduction in fitness against dishonest signaling strains. Also, the concept of the Least Expensive Reliable Signal is introduced and applied to study how the properties of the regulated phenotype affect the metabolic investment in signaling needed by the quorum sensing bacteria to withstand dishonest signaling.

A Game Theoretic Analysis of the Dual Function of Antibiotics.

There are two major views toward the role of antibiotics in microbial social interactions. The classical view is that antibiotics serve as weapons, produced by a bacterial species, at a significant cost, to inhibit the growth of its competitors. This view is supported by observations that antibiotics are usually upregulated by stress responses that infer the intensity of ecological competition, such as nutrient limitation and cellular damage, which point out to a competitive role for antibiotics. The other ecological function frequently assigned to antibiotics is that they serve as signaling molecules which regulate the collective behavior of a microbial community. Here, we investigate the conditions at which a weapon can serve as a signal in the context of microbial competition. We propose that an antibiotic will serve as a signal whenever a potential alteration of the growth behavior of the signal receiver, in response to a subinhibitory concentration (SIC) of the antibiotic, reduces the competitive pressure on the signal producer. This in turn would lead to avoiding triggering the stress mechanisms of the signal producer responsible for further antibiotics production. We show using individual-based modeling that this reduction of competitive pressure on the signal producer can happen through two main classes of responses by the signal recipient: competition tolerance, where the recipient reduces its competitive impact on the signal producer by switching to a low growth rate/ high yield strategy, and niche segregation, where the recipient reduces the competitive pressure on the signal producer by reducing their niche overlap. Our hypothesis proposes that antibiotics serve as signals out of their original function as weapons in order to reduce the chances of engaging in fights that would be costly to both the antibiotic producer as well as to its competitors.

Simulation of Escherichia coli Dynamics in Biofilms and Submerged Colonies with an Individual-Based Model Including Metabolic Network Information.

Clustered microbial communities are omnipresent in the food industry, e.g., as colonies of microbial pathogens in/on food media or as biofilms on food processing surfaces. These clustered communities are often characterized by metabolic differentiation among their constituting cells as a result of heterogeneous environmental conditions in the cellular surroundings. This paper focuses on the role of metabolic differentiation due to oxygen gradients in the development of Escherichia coli cell communities, whereby low local oxygen concentrations lead to cellular secretion of weak acid products. For this reason, a metabolic model has been developed for the facultative anaerobe E. coli covering the range of aerobic, microaerobic, and anaerobic environmental conditions. This metabolic model is expressed as a multiparametric programming problem, in which the influence of low extracellular pH values and the presence of undissociated acid cell products in the environment has been taken into account. Furthermore, the developed metabolic model is incorporated in MICRODIMS, an in-house developed individual-based modeling framework to simulate microbial colony and biofilm dynamics. Two case studies have been elaborated using the MICRODIMS simulator: (i) biofilm growth on a substratum surface and (ii) submerged colony growth in a semi-solid mixed food product. In the first case study, the acidification of the biofilm environment and the emergence of typical biofilm morphologies have been observed, such as the mushroom-shaped structure of mature biofilms and the formation of cellular chains at the exterior surface of the biofilm. The simulations show that these morphological phenomena are respectively dependent on the initial affinity of pioneer cells for the substratum surface and the cell detachment process at the outer surface of the biofilm. In the second case study, a no-growth zone emerges in the colony center due to a local decline of the environmental pH. As a result, cellular growth in the submerged colony is limited to the colony periphery, implying a linear increase of the colony radius over time. MICRODIMS has been successfully used to reproduce complex dynamics of clustered microbial communities.

Molecular and serological prevalence of Babesia bigemina and Babesia bovis in cattle and water buffalos under small-scale dairy farming in Beheira and Faiyum Provinces, Egypt.

In order to determine the molecular and serological prevalence of Babesia bigemina and Babesia bovis, a total of 247 blood samples were collected from cattle and water buffalos in Beheira and Faiyum Provinces in Egypt and examined by nested polymerase chain reaction (nPCR) and enzyme-linked immunosorbent assay (ELISA). In cattle, the prevalence of B. bigemina and B. bovis was 5.30% and 3.97% by nPCR and 10.60% and 9.27% by ELISA, respectively, whereas those of water buffalos were 10.42% and 4.17% by nPCR and 15.63% and 11.46% by ELISA, respectively. Statistically significant differences in the prevalence of the two infections were observed on the basis of age and health status. Sequencing analysis revealed two genotypes for B. bovis spherical body protein-4. In conclusion, the current data provide valuable information regarding the epidemiology of B. bigemina and B. bovis infections in cattle and water buffalos from Egypt, which can be employed in developing future strategies for disease management and control.