Group A streptococcal (GAS; aka Streptococcus pyogenes) meningitis is a fulminant disease associated with high morbidity and mortality. To elucidate the mechanisms underlying the invasiveness of GAS in meningitis, we compared GAS isolates derived from five cases of meningitis to otitis and colonizing isolates. We did not observe differences in adherence to and invasion of human brain microvascular endothelial cells, virulence factors activity, or barrier disruption.
View Article and Find Full Text PDFInfective endocarditis (IE) is a life-threatening biofilm-associated infection, yet the factors driving biofilm formation remain poorly understood. Here, we identified the Fsr quorum sensing (QS) system of as a potent negative regulator of IE pathogenesis. Using microfluidic and models, we show that Fsr is induced in late IE when bacteria become shielded from blood flow.
View Article and Find Full Text PDFIntroduction: The ability to detect pathogenic bacteria before the onsets of severe respiratory symptoms and to differentiate bacterial infection allows to improve patient-tailored treatment leading to a significant reduction in illness severity, comorbidity as well as antibiotic resistance. As such, this study refines the application of the non-invasive Secondary Electrospray Ionization-High Resolution Mass Spectrometry (SESI-HRMS) methodology for real-time and early detection of human respiratory bacterial pathogens in the respiratory tract of a mouse infection model.
Methods: A real-time analysis of changes in volatile metabolites excreted by mice undergoing a lung infection by Staphylococcus aureus or Streptococcus pneumoniae were evaluated using a SESI-HRMS instrument.
Background: Necrotizing soft tissue infections (NSTIs) are often caused by group A (GAS). As the number of invasive GAS infections decreased during the coronavirus disease 2019 (COVID-19) pandemic restrictions, this study aimed to compare the occurrence of GAS-NSTIs before, during, and after the COVID-19 pandemic restrictions.
Methods: This retrospective cohort study included adult patients with NSTIs admitted to the intensive care unit (ICU) of the University Hospital Zurich, Switzerland, from July 2008 to December 2023.
Group A (GAS) necrotizing fasciitis (NF) is a difficult-to-treat bacterial infection associated with high morbidity and mortality despite extensive surgery and targeted antibiotic treatment. Difficult-to-treat infections are often characterized by the presence of bacteria surviving prolonged antibiotic exposure without displaying genetic resistance, referred to as persisters. In the present study, we investigated the presence of GAS persisters in tissue freshly debrided from patients as well as in an mouse model of NF and examined the phenomenon of antibiotic tolerance.
View Article and Find Full Text PDFThe surgical repair of a ruptured tendon faces two major problems: specifically increased fibrous adhesion to the surrounding tissue and inferior mechanical properties of the scar tissue compared to the native tissue. Bacterial attachment to implant materials is an additional problem as it might lead to severe infections and impaired recovery. To counteract adhesion formation, two novel implant materials were fabricated by electrospinning, namely, a random fiber mesh containing hyaluronic acid (HA) and poly(ethylene oxide) (PEO) in a ratio of 1:1 (HA/PEO 1:1) and 1:4 (HA/PEO 1:4), respectively.
View Article and Find Full Text PDFBacterial infections are a growing global healthcare concern, as an estimated annual 4.95 million deaths are associated with antimicrobial resistance (AMR). Methicillin-resistant is one of the deadliest pathogens and a high-priority pathogen according to the World Health Organization.
View Article and Find Full Text PDFBackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.
View Article and Find Full Text PDFAntimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates.
View Article and Find Full Text PDFAntibiotic resistance and tolerance are substantial healthcare-related problems, hampering effective treatment of bacterial infections. Mutations in the phosphodiesterase GdpP, which degrades cyclic di-3', 5'-adenosine monophosphate (c-di-AMP), have recently been associated with resistance to beta-lactam antibiotics in clinical isolates. In this study, we show that high c-di-AMP levels decreased the cell size and increased the cell wall thickness in mutant strains.
View Article and Find Full Text PDFIn microbiology, accessing single-cell information within large populations is pivotal. Here we introduce bio-sCAPA, a technique for patterning bacterial cells in defined geometric arrangements and monitoring their growth in various nutrient environments. We demonstrate bio-sCAPA with a study of subpopulations of antibiotic-tolerant bacteria, known as persister cells, which can survive exposure to high doses of antibiotics despite lacking any genetic resistance to the drug.
View Article and Find Full Text PDFViruses have been present during all evolutionary steps on earth and have had a major effect on human history. Viral infections are still among the leading causes of death. Another public health concern is the increase of non-communicable metabolic diseases in the last four decades.
View Article and Find Full Text PDFBackground: Pseudomonas aeruginosa and other Gram-negative bacteria have the ability to persist in moist environments in healthcare settings, but their spread from these areas can result in outbreaks of healthcare-associated infections.
Methods: This study reports the investigation and containment of a multi-drug-resistant P. aeruginosa outbreak in three intensive care units of a Swiss university hospital.
Staphylococcus aureus carriage is a risk factor for invasive infections. Unique genetic elements favoring the transition from colonizing to invasive phenotype have not yet been identified, and phenotypic adaptation traits are understudied. We therefore assessed phenotypic and genotypic profiles of 11 S.
View Article and Find Full Text PDFAutophagy serves an innate immune function in defending the host against invading bacteria, including group A (GAS). Autophagy is regulated by numerous host proteins, including the endogenous negative regulator calpain, a cytosolic protease. Globally disseminated serotype M1T1 GAS strains associated with high invasive disease potential express numerous virulence factors and resist autophagic clearance.
View Article and Find Full Text PDFRegulated cell death (RCD) and the concomitant release of extracellular traps by neutrophils (NETs) constitute an important antibacterial effector response. Usually, the dynamic processes of RCD and NETs release are assessed independently of each other by either unspecific or time-consuming methods. Here, we describe a flow cytometry-based high-throughput analysis method incorporating neutrophil RCD and NETs release with visual live-imaging conformation upon ex vivo bacterial challenge.
View Article and Find Full Text PDFAims Of The Study: The goal of this descriptive study was to assess the performance as well as the extent of the clinical impact of rapid automated antimicrobial susceptibility testing in patients with bacteraemia due to Enterobacterales. We also aimed to analyse how rapid automated antimicrobial susceptibility testing influences clinical decision-making.
Methods: This single-centre study conducted at the University Hospital of Zurich included data from all consecutive patients with Enterobacterales bacteraemia from November 2019 to October 2020.