SUMMARY and are human pathobionts that exhibit a dual lifestyle as commensal and pathogenic bacteria. The pathogenic lifestyle is associated with specific conditions involving host susceptibility and intestinal overgrowth or the use of a medical device. Although the virulence of appears to benefit from its antimicrobial resistance, is recognized for its higher pathogenic potential.
View Article and Find Full Text PDFHost-acting compounds are emerging as potential alternatives to combating antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for treating chronic myelogenous leukemia, does not possess any antibiotic activity but enhances macrophage responses to bacterial infection. In vitro, bosutinib stimulates murine and human macrophages to kill bacteria more effectively.
View Article and Find Full Text PDFAntibiotic resistance critically limits treatment options for infection caused by opportunistic pathogens such as enterococci. Here, we investigate the antibiotic and immunological activity of the anticancer agent mitoxantrone (MTX) in vitro and in vivo against vancomycin-resistant (VRE). We show that, in vitro, MTX is a potent antibiotic against Gram-positive bacteria through induction of reactive oxygen species and DNA damage.
View Article and Find Full Text PDFEnterococcus faecalis is a frequent opportunistic pathogen of wounds, whose infections are associated with biofilm formation, persistence, and recalcitrance toward treatment. We have previously shown that E. faecalis wound infection persists for at least 7 days.
View Article and Find Full Text PDFCurr Opin Microbiol
October 2021
Biofilm formation is a multifactorial process and often a multi-species endeavour that involves complex signalling networks, chemical gradients, bacterial adhesion, and production or acquisition of matrix components. Antibiotics remain the main choice when treating bacterial biofilm-associated infections despite their intrinsic tolerance to antimicrobials, and propensity for acquisition and rapid dissemination of antimicrobial resistance within the biofilm. Eliminating hard to treat biofilm-associated infections that are antibiotic resistant will demand a holistic and multi-faceted approach, targeting multiple stages of biofilm formation, many of which are already in development.
View Article and Find Full Text PDFMeningococcal lipoprotein, Factor H binding protein (FHbp), is the sole antigen of the Trumenba vaccine (Pfizer) and one of four antigens of the Bexsero vaccine (GSK) targeting serogroup B isolates. Lipidation of FHbp is assumed to occur for all isolates. We show in the majority of a collection of United Kingdom isolates (1742/1895) non-synonymous single nucleotide polymorphisms (SNPs) in the signal peptide (SP) of FHbp.
View Article and Find Full Text PDFThe serine/arginine-rich protein kinase 2 (SRPK2) has been reported as upregulated in several cancer types, with roles in hallmarks such as cell migration, growth, and apoptosis. These findings have indicated that SRPK2 is a promising emerging target in drug discovery initiatives. Although high-resolution models are available for SRPK2 (PDB 2X7G), they have been obtained with a heavily truncated recombinant protein version (~50% of the primary structure), due to the presence of long intrinsically unstructured regions.
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