Validated Preclinical Mouse Model for Therapeutic Testing against Multidrug-Resistant Pseudomonas aeruginosa Strains.

The rise in infections caused by antibiotic-resistant bacteria is outpacing the development of new antibiotics. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are a group of clinically important bacteria that have developed resistance to multiple antibiotics and are commonly referred to as multidrug resistant (MDR). The medical and research communities have recognized that, without new antimicrobials, infections by MDR bacteria will soon become a leading cause of morbidity and death.

Treponema denticola Induces Interleukin-36γ Expression in Human Oral Gingival Keratinocytes via the Parallel Activation of NF-κB and Mitogen-Activated Protein Kinase Pathways.

The oral epithelial barrier acts as both a physical barrier to the abundant oral microbiome and a sentry for the immune system that, in health, constrains the accumulation of the polymicrobial plaque biofilm. The immune homeostasis during gingivitis that is largely protective becomes dysregulated, unproductive, and destructive to gingival tissue as periodontal disease progresses to periodontitis. The progression to periodontitis is associated with the dysbiosis of the oral microbiome, with increasing prevalences and abundances of periodontal pathogens such as Treponema denticola.

Porphyromonas gingivalis Tyrosine Kinase Is a Fitness Determinant in Polymicrobial Infections.

Many pathogenic microbial ecosystems are polymicrobial, and community function can be shaped by interbacterial interactions. Little is known, however, regarding the genetic determinants required for fitness in heterotypic community environments. In periodontal diseases, Porphyromonas gingivalis is a primary pathogen, but only within polymicrobial communities.

Proteolytic Activity-Independent Activation of the Immune Response by Gingipains from Porphyromonas gingivalis.

Porphyromonas gingivalis, a keystone pathogen in periodontitis (PD), produces cysteine proteases named gingipains (RgpA, RgpB, and Kgp), which strongly affect the host immune system. The range of action of gingipains is extended by their release as components of outer membrane vesicles, which efficiently diffuse into surrounding gingival tissues. However, away from the anaerobic environment of periodontal pockets, increased oxygen levels lead to oxidation of the catalytic cysteine residues of gingipains, inactivating their proteolytic activity.

Rapid, Efficient, and Cost-Effective Gene Editing of Enterococcus faecium with CRISPR-Cas12a.

Considered a serious threat by the Centers for Disease Control and Prevention, multidrug-resistant Enterococcus faecium is an increasing cause of hospital-acquired infection. Here, we provide details on a single-plasmid CRISPR-Cas12a system for generating clean deletions and insertions. Single manipulations were carried out in under 2 weeks, with successful deletions/insertions present in >80% of the clones tested.

Novel Antifungal Activity of Q-Griffithsin, a Broad-Spectrum Antiviral Lectin.

There is a rising global incidence of strains with high levels of resistance to fluconazole and other antifungal drugs, hence the need for novel antifungal treatment strategies. Here, we describe the first evidence of antifungal activity of Q-Griffithsin (Q-GRFT), a recombinant oxidation-resistant variant of Griffithsin, a marine red algal lectin with broad-spectrum antiviral activity. We demonstrated that Q-GRFT binds to α-mannan in the Candida albicans cell wall.