0000000000823721
AUTHOR
Sari Mattila
Conjugative ESBL plasmids differ in their potential to rescue susceptible bacteria via horizontal gene transfer in lethal antibiotic concentrations.
Conjugative ESBL plasmids differ in their potential to rescue susceptible bacteria via horizontal gene transfer in lethal antibiotic concentrations
On-Demand Isolation of Bacteriophages Against Drug-Resistant Bacteria for Personalized Phage Therapy
Bacteriophages are bacterial viruses, capable of killing even multi-drug resistant bacterial cells. For this reason, therapeutic use of phages is considered as a possible alternative to conventional antibiotics. However, phages are very host specific in comparison to wide-spectrum antibiotics and thus preparation of phage-cocktails beforehand against pathogens can be difficult. In this study, we evaluate whether it may be possible to isolate phages on-demand from environmental reservoir. We attempted to enrich infectious bacteriophages from sewage against nosocomial drug-resistant bacterial strains of different medically important species in order to evaluate the probability of discovering …
Midbiotics : conjugative plasmids for genetic engineering of natural gut flora
ABSTRACTThe possibility to modify gut bacterial flora has become an important goal, and various approaches are used to achieve desirable communities. However, the genetic engineering of existing microbes in the gut, which are already compatible with the rest of the community and host immune system, has not received much attention. Here, we discuss and experimentally evaluate the possibility to use modified and mobilizable CRISPR-Cas9-endocing plasmid as a tool to induce changes in bacterial communities. This plasmid system (briefly midbiotic) is delivered from bacterial vector into target bacteria via conjugation. Compared to, for example, bacteriophage-based applications, the benefits of c…
Chasing the Origin of Viruses: Capsid-Forming Genes as a Life-Saving Preadaptation within a Community of Early Replicators
Virus capsids mediate the transfer of viral genetic information from one cell to another, thus the origin of the first viruses arguably coincides with the origin of the viral capsid. Capsid genes are evolutionarily ancient and their emergence potentially predated even the origin of first free-living cells. But does the origin of the capsid coincide with the origin of viruses, or is it possible that capsid-like functionalities emerged before the appearance of true viral entities? We set to investigate this question by using a computational simulator comprising primitive replicators and replication parasites within a compartment matrix. We observe that systems with no horizontal gene transfer…
Small things matter : of phages and antibiotic resistance conferring plasmids
Viruses and plasmids are small units of genetic material dependent on cells either transiently or continuously. Intriguingly, stories of these small entities intertwine in antibiotic resistance crisis. Horizontal gene transfer enables bacteria to respond rapidly to chances in their environment. Anthropogenic consumption of antibiotics induces the travel of resistance encoding genes mainly as passengers of conjugative plasmids. In this thesis, I demonstrate that clinically important resistance plasmids could evolutionarily rescue susceptible bacteria under lethal antibiotic concentrations. If mobile resistance genes are available in surrounding community, administration of high doses of anti…
Evolutionary rescue of bacteria via horizontal gene transfer under a lethal β-lactam concentration
β-Lactams are a commonly used class of bactericidal antibiotics. The number of β-lactam-resistant pathogens is constantly increasing in hospitals around the world. Interestingly, most of the β-lactam-resistant bacteria carry mobile genetic elements, such as conjugative plasmids, that render the pathogen resistant. These elements mediate their own transfer from one bacterium to another, producing new resistant strains via horizontal gene transfer. Here we investigated whether it is possible that transfer of the resistance element from another bacterium may evolutionarily rescue a susceptible bacterium exposed to a lethal concentration of the β-lactam ampicillin. Indeed, the rescuing occurs e…
Probing protein interactions in the membrane-containing virus PRD1.
PRD1 is a Gram-negative bacteria infecting complex tailless icosahedral virus with an inner membrane. This type virus of the family Tectiviridae contains at least 18 structural protein species, of which several are membrane associated. Vertices of the PRD1 virion consist of complexes recognizing the host cell, except for one special vertex through which the genome is packaged. Despite extensive knowledge of the overall structure of the PRD1 virion and several individual proteins at the atomic level, the locations and interactions of various integral membrane proteins and membrane-associated proteins still remain a mystery. Here, we demonstrated that blue native PAGE can be used to probe pro…
Scoping the effectiveness and evolutionary obstacles in using plasmid-dependent phages to fight antibiotic resistance
Aim: To investigate the potential evolutionary obstacles in the sustainable therapeutic use of plasmid-dependent phages to control the clinically important conjugative plasmid-mediated dissemination of antibiotic resistance genes to pathogenic bacteria. Materials & methods: The lytic plasmid-dependent phage PRD1 and the multiresistance conferring plasmid RP4 in an Escherichia coli host were utilized to assess the genetic and phenotypic changes induced by combined phage and antibiotic selection. Results & conclusions: Resistance to PRD1 was always coupled with either completely lost or greatly reduced conjugation ability. Reversion to full conjugation efficiency was found to be rare…
Data from: Black Queen evolution and trophic interactions determine plasmid survival after the disruption of conjugation network
Mobile genetic elements such as conjugative plasmids are responsible for antibiotic resistant phenotypes in many bacterial pathogens. The ability to conjugate, the presence of antibiotics and ecological interactions all have a notable role in the persistence of plasmids in bacterial populations. Here, we set out to investigate the contribution of these factors when the conjugation network was disturbed by a plasmid-dependent bacteriophage. Phage alone effectively caused the population to lose plasmids, thus rendering them susceptible to antibiotics. Leakiness of the antibiotic resistance mechanism allowing Black Queen evolution (i.e. race to the bottom) was a more significant factor over an…