Antimicrobial susceptibility testing of invasive isolates of Streptococcus pneumoniae from Canadian patients: the SAVE study, 2011-2020.

Objectives: To assess the antimicrobial susceptibility of 14 138 invasive Streptococcus pneumoniae isolates collected in Canada from 2011 to 2020.

Methods: Antimicrobial susceptibility testing was performed using the CLSI M07 broth microdilution reference method. MICs were interpreted using 2022 CLSI M100 breakpoints.

The ColR/S two-component system is a conserved determinant of host association across Pseudomonas species.

Members of the bacterial genus Pseudomonas form mutualistic, commensal, and pathogenic associations with diverse hosts. The prevalence of host association across the genus suggests that symbiosis may be a conserved ancestral trait and that distinct symbiotic lifestyles may be more recently evolved. Here we show that the ColR/S two-component system, part of the Pseudomonas core genome, is functionally conserved between Pseudomonas aeruginosa and Pseudomonas fluorescens.

Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens.

Host defense peptides (HDPs) represent an alternative way to address the emergence of antibiotic resistance. Crocodylians are interesting species for the study of these molecules because of their potent immune system, which confers high resistance to infection. Profile hidden Markov models were used to screen the genomes of four crocodylian species for encoded cathelicidins and eighteen novel sequences were identified.

BosR: A novel biofilm-specific regulator in .

Biofilms are the most common cause of bacterial infections in humans and notoriously hard to treat due to their ability to withstand antibiotics and host immune defenses. To overcome the current lack of effective antibiofilm therapies and guide future design, the identification of novel biofilm-specific gene targets is crucial. In this regard, transcriptional regulators have been proposed as promising targets for antimicrobial drug design.

Competition between Pseudomonas aeruginosa and Staphylococcus aureus is dependent on intercellular signaling and regulated by the NtrBC two-component system.

Pseudomonas aeruginosa and Staphylococcus aureus are often comorbid human pathogens, isolated from expectorated sputum of cystic fibrosis patients and chronically infected wounds. Prior studies revealed a competitive advantage of P. aeruginosa over S.

Self-Assembly of Antimicrobial Peptoids Impacts Their Biological Effects on Bacterial Pathogens.

Antimicrobial peptides (AMPs) are promising pharmaceutical candidates for the prevention and treatment of infections caused by multidrug-resistant pathogens, which are responsible for the majority of hospital-acquired infections. Clinical translation of AMPs has been limited, in part by apparent toxicity on systemic dosing and by instability arising from susceptibility to proteolysis. Peptoids (sequence-specific oligo--substituted glycines) resist proteolytic digestion and thus are of value as AMP mimics.

Multifunctional Antibiotic-Host Defense Peptide Conjugate Kills Bacteria, Eradicates Biofilms, and Modulates the Innate Immune Response.

Effective anti-infective therapies are required to offset the rise in antibiotic resistance. A novel vancomycin-innate defense regulator conjugate (V-IDR1018) was constructed with multimodal functionality, including bacterial killing, biofilm eradication, and immune modulation. The conjugate killed bacteria within 30 min, exhibited potent activity against persister cells, and showed no susceptibility to antimicrobial resistance in tissue culture assays.

NtrBC Selectively Regulates Host-Pathogen Interactions, Virulence, and Ciprofloxacin Susceptibility of .

is a metabolically versatile opportunistic pathogen capable of infecting distinct niches of the human body, including skin wounds and the lungs of cystic fibrosis patients. Eradication of infection is becoming increasingly difficult due to the numerous resistance mechanisms it employs. Adaptive resistance is characterized by a transient state of decreased susceptibility to antibiotic therapy that is distinct from acquired or intrinsic resistance, can be triggered by various environmental stimuli and reverted by removal of the stimulus.

Antibiofilm activity of host defence peptides: complexity provides opportunities.

Host defence peptides (HDPs) are integral components of innate immunity across all living organisms. These peptides can exert direct antibacterial effects, targeting planktonic cells (referred to as antimicrobial peptides), and exhibit antibiofilm (referred to as antibiofilm peptides), antiviral, antifungal and host-directed immunomodulatory activities. In this Review, we discuss how the complex functional attributes of HDPs provide many opportunities for the development of antimicrobial therapeutics, focusing particularly on their emerging antibiofilm properties.

Peptide 1018 inhibits swarming and influences Anr-regulated gene expression downstream of the stringent stress response in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that causes considerable human morbidity and mortality, particularly in nosocomial infections and individuals with cystic fibrosis. P. aeruginosa can adapt to surface growth by undergoing swarming motility, a rapid multicellular movement that occurs on viscous soft surfaces with amino acids as a nitrogen source.

Murine Model of Sinusitis Infection for Screening Antimicrobial and Immunomodulatory Therapies.

The very common condition of sinusitis is characterized by persistent inflammation of the nasal cavity, which contributes to chronic rhinosinusitis and morbidity of cystic fibrosis patients. Colonization by opportunistic pathogens such as and triggers inflammation that is exacerbated by defects in the innate immune response. Pathophysiological mechanisms underlying initial colonization of the sinuses are not well established.

Cathelicidin Host Defense Peptides and Inflammatory Signaling: Striking a Balance.

Host-defense peptides (HDPs) are vital components of innate immunity in all vertebrates. While their antibacterial activity toward bacterial cells was the original focus for research, their ability to modulate immune and inflammatory processes has emerged as one of their major functions in the host and as a promising approach from which to develop novel therapeutics targeting inflammation and innate immunity. In this review, with particular emphasis on the cathelicidin family of peptides, the roles of natural HDPs are examined in managing immune activation, cellular recruitment, cytokine responses, and inflammation in response to infection, as well as their contribution(s) to various inflammatory disorders and autoimmune diseases.

NtrBC Regulates Invasiveness and Virulence of During High-Density Infection.

is an opportunistic pathogen that is a major cause of nosocomial and chronic infections contributing to morbidity and mortality in cystic fibrosis patients. One of the reasons for its success as a pathogen is its ability to adapt to a broad range of circumstances. Here, we show the involvement of the general nitrogen regulator NtrBC, which is structurally conserved but functionally diverse across species, in pathogenic and adaptive states of .

Dismantling the bacterial virulence program.

In the face of rising antimicrobial resistance, there is an urgent need for the development of efficient and effective anti-infective compounds. Adaptive resistance, a reversible bacterial phenotype characterized by the ability to surmount antibiotic challenge without mutation, is triggered to cope in situ with several stressors and is very common clinically. Thus, it is important to target stress-response effectors that contribute to in vivo adaptations and associated lifestyles such as biofilm formation.

Characterization of novel kainic acid analogs as inhibitors of select microglial functions.

Alzheimer's disease (AD) is characterized by abnormal accumulation of extracellular amyloid beta protein (Aβ) plaques and intracellular neurofibrillary tangles, as well as by a state of chronic inflammation in the central nervous system (CNS). Adverse activation of microglia, the brain immune cells, is believed to contribute to AD pathology including excessive neuronal death. Thus, normalizing immune functions of microglia could slow neurodegeneration, and identification of novel compounds capable of modifying microglial functions is an important goal.