Nanofilament immunotherapy induces potent antitumor vaccine responses.

Background: Checkpoint inhibitors revolutionized cancer treatment by potentiating antitumor immune responses. However, many patients do not respond to these therapies, often due to the lack of a pre-existing immune response against cancer cells. Developing immunotherapies that promote cancer-cell antigen recognition, and the initiation of antitumor immune responses could thus improve response rates.

Isolation of a -positive strain in Israel predating the earliest observations from India.

Unlabelled: , the most prevalent carbapenemase among carbapenem-resistant Enterobacteriaceae, is thought to have emerged in India, as its initial detection in 2008 was linked to this country, and subsequent retrospective surveys had so far established the earliest -positive strains to be isolated in India in 2005. Molecular dating and analyses suggest emerged within species decades prior to 2005 on a Tn transposon. Despite early reports of elevated rates of carbapenem-resistant species in Israel starting in the 1990s, limited molecular data are available from this location.

Diagnosis and mitigation of the systemic impact of genome reduction in DGF-298.

Unlabelled: Microorganisms with simplified genomes represent interesting cell chassis for systems and synthetic biology. However, genome reduction can lead to undesired traits, such as decreased growth rate and metabolic imbalances. To investigate the impact of genome reduction on strain DGF-298, a strain in which ~ 36% of the genome has been removed, we reconstructed a strain-specific metabolic model (AC1061), investigated the regulation of gene expression using iModulon-based transcriptome analysis, and performed adaptive laboratory evolution to let the strain correct potential imbalances that arose during its simplification.

Earliest observation of the tetracycline destructase ).

Unlabelled: Tigecycline is an antibiotic of last resort for infections with carbapenem-resistant . Plasmids harboring variants of the tetracycline destructase gene promote rising tigecycline resistance rates. We report the earliest observation of ) in a clinical strain predating tigecycline's commercialization, suggesting selective pressures other than tigecycline contributed to its emergence.

: a near-minimal model organism for systems and synthetic biology.

is an emerging model organism for systems and synthetic biology due to its small genome (∼800 kb) and fast growth rate. While was isolated and first described almost 40 years ago, many important aspects of its biology have long remained uncharacterized due to technological limitations, the absence of dedicated molecular tools, and since this bacterial species has not been associated with any disease. However, the publication of the first genome in 2004 paved the way for a new era of research fueled by the rise of systems and synthetic biology.

Synthesis of a Conjugative System from Human Gut Metagenomic Data for Targeted Delivery of Cas9 Antimicrobials.

Metagenomic sequences represent an untapped source of genetic novelty, particularly for conjugative systems that could be used for plasmid-based delivery of Cas9-derived antimicrobial agents. However, unlocking the functional potential of conjugative systems purely from metagenomic sequences requires the identification of suitable candidate systems as starting scaffolds for DNA synthesis. Here, we developed a bioinformatics approach that searches through the metagenomic "trash bin" for genes associated with conjugative systems present on contigs that are typically excluded from common metagenomic analysis pipelines.

Complete sequence of the genome-reduced DGF-298.

We report the complete genome sequence and annotation of DGF-298, a genome-reduced strain with interesting properties for systems and synthetic biology. DGF-298 has a single circular chromosome of 2,991,126 bp and 2,831 genes, including 2,691 coding sequences, with a mean G + C content of ~51%.

Small-Colony Variants from Airways of Adult Cystic Fibrosis Patients as Precursors of Adaptive Antibiotic-Resistant Mutations.

Prototypic and their small-colony variants (SCVs) are predominant in cystic fibrosis (CF), but the interdependence of these phenotypes is poorly understood. We characterized isolates from adult CF patients over several years. Of 18 -positive patients (58%), 13 (72%) were positive for SCVs.

Enabling low-cost and robust essentiality studies with high-throughput transposon mutagenesis (HTTM).

Transposon-insertion sequencing (TIS) methods couple high density transposon mutagenesis with next-generation sequencing and are commonly used to identify essential or important genes in bacteria. However, this approach can be work-intensive and sometimes expensive depending on the selected protocol. The difficulty to process a high number of samples in parallel using standard TIS protocols often restricts the number of replicates that can be performed and limits the deployment of this technique to large-scale projects studying gene essentiality in various strains or growth conditions.

The Type IV Pilus of Plasmid TP114 Displays Adhesins Conferring Conjugation Specificity and Is Important for DNA Transfer in the Mouse Gut Microbiota.

Type IV pili (T4P) are common bacterial surface appendages involved in different biological processes such as adherence, motility, competence, pathogenesis, and conjugation. In this work, we describe the T4P of TP114, an IncI2 enterobacterial conjugative plasmid recently shown to disseminate at high rates in the mouse intestinal tract. This pilus is composed of the major PilS and minor PilV pilins that are both important for conjugation in broth and in the gut microbiota but not on a solid support.

High-efficiency delivery of CRISPR-Cas9 by engineered probiotics enables precise microbiome editing.

Antibiotic resistance threatens our ability to treat infectious diseases, spurring interest in alternative antimicrobial technologies. The use of bacterial conjugation to deliver CRISPR-cas systems programmed to precisely eliminate antibiotic-resistant bacteria represents a promising approach but requires high in situ DNA transfer rates. We have optimized the transfer efficiency of conjugative plasmid TP114 using accelerated laboratory evolution.

An engineered Mycoplasma pneumoniae to fight Staphylococcus aureus.

Bacterial infections are commonly treated with antimicrobials, but the rise of multi-drug resistance and the presence of biofilms can compromise treatment efficacy. Recently, new approaches using live bacteria or engineered microorganisms have gained attention in the fight against several diseases. In their recent work, Lluch-Senar and colleagues (Garrido et al, 2021) genetically modified the lung pathogen Mycoplasma pneumoniae to attenuate its virulence and secrete antibiofilm and bactericidal enzymes.

Relative virulence of Staphylococcus aureus bovine mastitis strains representing the main Canadian spa types and clonal complexes as determined using in vitro and in vivo mastitis models.

Staphylococcus aureus is one of the main pathogens leading to both clinical and subclinical bovine mastitis in dairy cattle. Prediction of disease evolution based on the characteristics of Staph. aureus isolates that cause intramammary infections and understanding the host-pathogen interactions may improve management of mastitis in dairy herds.

Molecular Mechanisms Influencing Bacterial Conjugation in the Intestinal Microbiota.

Bacterial conjugation is a widespread and particularly efficient strategy to horizontally disseminate genes in microbial populations. With a rich and dense population of microorganisms, the intestinal microbiota is often considered a fertile environment for conjugative transfer and a major reservoir of antibiotic resistance genes. In this mini-review, we summarize recent findings suggesting that few conjugative plasmid families present in transfer at high rates in the gut microbiota.

Natural climate solutions for Canada.

Alongside the steep reductions needed in fossil fuel emissions, natural climate solutions (NCS) represent readily deployable options that can contribute to Canada's goals for emission reductions. We estimate the mitigation potential of 24 NCS related to the protection, management, and restoration of natural systems that can also deliver numerous co-benefits, such as enhanced soil productivity, clean air and water, and biodiversity conservation. NCS can provide up to 78.

Crucial role of Salmonella genomic island 1 master activator in the parasitism of IncC plasmids.

IncC conjugative plasmids and the multiple variants of Salmonella Genomic Island 1 (SGI1) are two functionally interacting families of mobile genetic elements commonly associated with multidrug resistance in the Gammaproteobacteria. SGI1 and its siblings are specifically mobilised in trans by IncC conjugative plasmids. Conjugative transfer of IncC plasmids is activated by the plasmid-encoded master activator AcaCD.

Integrative characterization of the near-minimal bacterium Mesoplasma florum.

The near-minimal bacterium Mesoplasma florum is an interesting model for synthetic genomics and systems biology due to its small genome (~ 800 kb), fast growth rate, and lack of pathogenic potential. However, fundamental aspects of its biology remain largely unexplored. Here, we report a broad yet remarkably detailed characterization of M.

Highly efficient gene transfer in the mouse gut microbiota is enabled by the Incl conjugative plasmid TP114.

The gut microbiota is a suspected hotspot for bacterial conjugation due to its high density and diversity of microorganisms. However, the contribution of different conjugative plasmid families to horizontal gene transfer in this environment remains poorly characterized. Here, we systematically quantified the transfer rates in the mouse intestinal tract for 13 conjugative plasmids encompassing 10 major incompatibility groups.

Bactericidal Activity of the Bacterial ATP Synthase Inhibitor Tomatidine and the Combination of Tomatidine and Aminoglycoside Against Persistent and Virulent Forms of .

Tomatidine (TO), a steroid alkaloid, exerts a strong bactericidal activity on the infection-persistent phenotype of , the small-colony variant (SCV), with a minimal inhibitory concentration (MIC) of 0.06 μg/ml. Also, the combination of TO to an aminoglycoside (AMG) shows a strong synergistic effect against prototypical (WT) (MIC 0.

[Whole genome transplantation: bringing natural or synthetic bacterial genomes back to life].

The development of synthetic genomics (SG) allowed the emergence of several groundbreaking techniques including the synthesis, assembly and engineering of whole bacterial genomes. The successful implantation of those methods, which culminated in the creation of JCVI-syn3.0 the first nearly minimal bacterium with a synthetic genome, mainly results from the use of the yeast Saccharomyces cerevisiae as a transient host for bacterial genome replication and modification.

[Synthetic chromosomes: rewriting the code of life].

The past decade has seen vast improvements in DNA synthesis and assembly methods. The creation of synthetic DNA molecules is becoming easier and more affordable, such that entire chromosomes can now be synthesized. These advances mark the beginning of synthetic genomics, a new discipline interested in the construction of complete genomes tailored for the study and application of biological systems.

Assembly of large mobilizable genetic cargo by double recombinase operated insertion of DNA (DROID).

There is an important need to develop new therapeutic tools to modulate the gene content of microbiomes. A potential strategy for microbiome engineering relies on the delivery of genetic payloads by conjugative plasmids. Yet, the introduction of large DNA molecules in conjugative plasmids can be challenging.