Pseudomonas aeruginosa Adaptation to Lungs of Cystic Fibrosis Patients Leads to Lowered Resistance to Phage and Protist Enemies

Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations

Nanotechnology intervention of the microbiome for cancer therapy

The microbiome is emerging as a key player and driver of cancer. Traditional modalities to manipulate the microbiome (for example, antibiotics, probiotics and microbiota transplants) have been shown to improve efficacy of cancer therapies in some cases, but issues such as collateral damage to the commensal microbiota and consistency of these approaches motivates efforts towards developing new technologies specifically designed for the microbiome–cancer interface. Considering the success of nanotechnology in transforming cancer diagnostics and treatment, nanotechnologies capable of manipulating interactions that occur across microscopic and molecular length scales in the microbiome and the tumour microenvironment have the potential to provide innovative strategies for cancer treatment. As such, opportunities at the intersection of nanotechnology, the microbiome and cancer are massive. In this Review, we highlight key opportunistic areas for applying nanotechnologies towards manipulating the microbiome for the treatment of cancer, give an overview of seminal work and discuss future challenges and our perspective on this emerging area

Phage-Bacterium War on Polymeric Surfaces: Can Surface-Anchored Bacteriophages Eliminate Microbial Infections?

These studies illustrate synthetic paths to covalently attach T1 and φ11 bacteriophages (phages) to inert polymeric surfaces while maintaining bacteriophage’s biological activities capable of killing deadly human pathogens. The first step involved formation of acid (COOH) groups on polyethylene (PE) and polytetrafluoroethylene (PTFE) surfaces using microwave plasma reactions in the presence of maleic anhydride, followed by covalent attachment of T1 and φ11 species via primary amine groups. The phages effectively retain their biological activity manifested by a rapid infection with their own DNA and effective destruction of Escherichia coli and Staphylococcus aureus human pathogens. These studies show that simultaneous covalent attachment of two biologically active phages effectively destroy both bacterial colonies and eliminate biofilm formation, thus offering an opportunity for an effective combat against multi-bacterial colonies as well as surface detections of other pathogens. [Image: see text

Phage or foe: an insight into the impact of viral predation on microbial communities

Since their discovery, bacteriophages have been traditionally regarded as the natural enemies of bacteria. However, recent advances in molecular biology techniques, especially data from “omics” analyses, have revealed that the interplay between bacterial viruses and their hosts is far more intricate than initially thought. On the one hand, we have become more aware of the impact of viral predation on the composition and genetic makeup of microbial communities thanks to genomic and metagenomic approaches. Moreover, data obtained from transcriptomic, proteomic, and metabolomic studies have shown that responses to phage predation are complex and diverse, varying greatly depending on the bacterial host, phage, and multiplicity of infection. Interestingly, phage exposure may alter different phenotypes, including virulence and biofilm formation. The complexity of the interactions between microbes and their viral predators is also evidenced by the link between quorum-sensing signaling pathways and bacteriophage resistance. Overall, new data increasingly suggests that both temperate and virulent phages have a positive effect on the evolution and adaptation of microbial populations. From this perspective, further research is still necessary to fully understand the interactions between phage and host under conditions that allow co-existence of both populations, reflecting more accurately the dynamics in natural microbial communities.Our work on bacteriophages was funded by grants AGL2015-65673-R (Ministry of Science and Innovation, Spain), EU ANIWHA ERA-NET BLAAT, GRUPIN14-139 (Program of Science, Technology and Innovation 2013-2017 and FEDER EU funds, Principado de Asturias, Spain). L.F. was awarded a “Marie Curie Clarin-Cofund” grant. P.G. and A.R. are members of the bacteriophage network FAGOMAII and the FWO Vlaanderen funded “Phagebiotics” research community (WO.016.14).Peer reviewe