Long-term experimental evolution decouples size and production costs in Escherichia coli.

Body size covaries with population dynamics across life's domains. Metabolism may impose fundamental constraints on the coevolution of size and demography, but experimental tests of the causal links remain elusive. We leverage a 60,000-generation experiment in which Escherichia coli populations evolved larger cells to examine intraspecific metabolic scaling and correlations with demographic parameters. Over the course of their evolution, the cells have roughly doubled in size relative to their ancestors. These larger cells have metabolic rates that are absolutely higher, but relative to their size, they are lower. Metabolic theory successfully predicted the relations between size, metabolism, and maximum population density, including support for Damuth's law of energy equivalence, such that populations of larger cells achieved lower maximum densities but higher maximum biomasses than populations of smaller cells. The scaling of metabolism with cell size thus predicted the scaling of size with maximum population density. In stark contrast to standard theory, however, populations of larger cells grew faster than those of smaller cells, contradicting the fundamental and intuitive assumption that the costs of building new individuals should scale directly with their size. The finding that the costs of production can be decoupled from size necessitates a reevaluation of the evolutionary drivers and ecological consequences of biological size more generally.

Pseudomonas aeruginosa utilizes the host-derived polyamine spermidine to facilitate antimicrobial tolerance.

Pseudomonas aeruginosa undergoes diversification during infection of the cystic fibrosis (CF) lung. Understanding these changes requires model systems that capture the complexity of the CF lung environment. We previously identified loss-of-function mutations in the 2-component regulatory system sensor kinase gene pmrB in P. aeruginosa from CF lung infections and from experimental infection of mice. Here, we demonstrate that, while such mutations lowered in vitro minimum inhibitory concentrations for multiple antimicrobial classes, this was not reflected in increased antibiotic susceptibility in vivo. Loss of PmrB impaired aminoarabinose modification of LPS, increasing the negative charge of the outer membrane and promoting uptake of cationic antimicrobials. However, in vivo, this could be offset by increased membrane binding of other positively charged molecules present in lungs. The polyamine spermidine readily coated the surface of PmrB-deficient P. aeruginosa, reducing susceptibility to antibiotics that rely on charge differences to bind the outer membrane and increasing biofilm formation. Spermidine was elevated in lungs during P. aeruginosa infection in mice and during episodes of antimicrobial treatment in people with CF. These findings highlight the need to study antimicrobial resistance under clinically relevant environmental conditions. Microbial mutations carrying fitness costs in vitro may be advantageous during infection, where host resources can be utilized.

Revisiting Antibiotic Resistance: Mechanistic Foundations to Evolutionary Outlook.

Antibiotics are the pivotal pillar of contemporary healthcare and have contributed towards its advancement over the decades. Antibiotic resistance emerged as a critical warning to public wellbeing because of unsuccessful management efforts. Resistance is a natural adaptive tool that offers selection pressure to bacteria, and hence cannot be stopped entirely but rather be slowed down. Antibiotic resistance mutations mostly diminish bacterial reproductive fitness in an environment without antibiotics; however, a fraction of resistant populations 'accidentally' emerge as the fittest and thrive in a specific environmental condition, thus favouring the origin of a successful resistant clone. Therefore, despite the time-to-time amendment of treatment regimens, antibiotic resistance has evolved relentlessly. According to the World Health Organization (WHO), we are rapidly approaching a 'post-antibiotic' era. The knowledge gap about antibiotic resistance and room for progress is evident and unified combating strategies to mitigate the inadvertent trends of resistance seem to be lacking. Hence, a comprehensive understanding of the genetic and evolutionary foundations of antibiotic resistance will be efficacious to implement policies to force-stop the emergence of resistant bacteria and treat already emerged ones. Prediction of possible evolutionary lineages of resistant bacteria could offer an unswerving impact in precision medicine. In this review, we will discuss the key molecular mechanisms of resistance development in clinical settings and their spontaneous evolution.

In-situ incorporation of highly dispersed silver nanoparticles in nanoporous carbon nitride for the enhancement of antibacterial activities.

Graphitic carbon nitride with suitably incorporated functionality has attracted much interest in the areas of environmental treatments, clean energy, sensing, and photocatalyst. However, the role of graphitic nanoporous carbon nitride (NCN) matrix from single carbon-nitrogen (C-N) source, aminoguanidine HCl as a precursor and close intimate contact between silver nanoparticles (Ag NPs) dispersed in NCN and bacteria has rarely been demonstrated. Herein, we demonstrate a nanostructure of Ag NPs-incorporated NCN sample (NCN@Ag) as an antibacterial agent against both wild type and the multidrug-resistant Escherichia coli (E. coli) pathogens. In-situ ultrasonication method was used to ensure the homogeneous mixing of the Ag NPs and a single C-N precursor at the molecular level so that pore size (PS) (9.17 nm) of SBA15 silica could be impregnated with ultrasonicated Ag NPs and a single C-N precursor. The porous structure, compositions, and structural information of the final nanocomposites were confirmed by using various analytical techniques such as XRD, TEM, BET surface area (SA) measurements, XPS, and UV. Then, the antibacterial activities of the NCN and NCN@Ag against both wild type and the multidrug-resistant Escherichia coli (E. coli) pathogens were also carried out and results from the in-vitro studies have shown the excellent bactericidal effect of the highly dispersed Ag NPs containing NCN@Ag sample against both E. coli strains. Results have confirmed that the antibacterial activity of the NCN@Ag sample is found to be higher than pure NCN, indicating that in-situ incorporated Ag NPs in NCN matrix have played significant role for enhancing antibacterial activities. Surprisingly, in the presence of NCN@Ag, the reduction in minimum inhibitory concentration (MIC) was higher (64-fold reduction) compared to its susceptible wild type (32-fold reduction) E. coli. These results indicate the potential application of NCN@Ag for inactivating infectious bacterial pathogens implicated in multidrug resistance.