Notes

Study involving amyloidosis instances between different free-living untamed and zoo park animals.
Rapid-growing-mycobacteria (RGM) are environmental organisms, which may cause infections in patients with particular risk factors.….Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. We recently reported that the antitubercular 4-halogenated benzoxaboroles are active against Mycobacterium abscessus. Here, we find that the non-halogenated benzoxaborole epetraborole, a clinical candidate developed for Gram negative infections, is also active against M. abscessus in vitro and in a mouse model of infection. This expands the repertoire of advanced lead compounds for the discovery of a benzoxaborole-based candidate to treat M. abscessus lung disease.Otilonium bromide is a poorly absorbed oral medication used to control irritable bowel syndrome. It is thought to act as a muscle relaxant in the intestine. Here we show that otilonium bromide has broad-spectrum antibacterial and antifungal activity, including against multi-drug resistant strains. Our results suggest otilonium bromide could act on enteric pathogens and may offer a new scaffold for poorly absorbed intestinal antimicrobial therapy.Qac efflux pumps from proteobacterial multidrug-resistant plasmids are integron-encoded and confer resistance to quaternary ammonium compound (QAC) antiseptics, however, many are uncharacterized and misannotated. A survey of >2000 plasmid-encoded qac identified 37 unique qac sequences that correspond to one of five representative motifs QacE, QacEΔ1, QacF/L, QacH/I, and QacG. Antimicrobial susceptibility testing of each cloned qac member in Escherichia coli, highlighted distinctive antiseptic susceptibility patterns that were most prominent when cells grew as biofilms.Background The major global health threat tuberculosis is caused by Mycobacterium tuberculosis (Mtb). Mtb has a complex cell envelope - a partially covalently linked composite of polysaccharides, peptidoglycan and lipids, including a mycolic acid layer - which conveys pathogenicity but also protects against antibiotics. Given previous successes in treating gram-positive and -negative infections with cell wall degrading enzymes, we investigated such approach for Mtb. Objectives (i) Development of an Mtb microtiter growth inhibition assay that allows undisturbed cell envelope formation, to overcome the invalidation of results by typical clumped Mtb-growth in surfactant-free assays. (ii) Exploring anti-Mtb potency of cell wall layer-degrading enzymes. (iii) Investigation of the concerted action of several such enzymes. Methods We inserted a bacterial luciferase-operon in an auxotrophic Mtb strain to develop a microtiter assay that allows proper evaluation of cell wall degrading anti-Mtb enzymes. We assessed growth-inhibition by enzymes (recombinant mycobacteriophage mycolic acid esterase (LysB), fungal α-amylase and human and chicken egg white lysozymes) and combinations thereof, in presence or absence of biopharmaceutically acceptable surfactant. Results Our biosafety level-2 assay identified both LysB and lysozymes as potent Mtb-inhibitors, but only in presence of surfactant. Moreover, most potent disruption of the mycolic acid hydrophobic barrier was obtained by the highly synergistic combination of LysB, α-amylase and polysorbate 80. Conclusions Synergistically acting cell wall degrading enzymes are potently inhibiting Mtb - which sets the scene for the design of specifically tailored antimycobacterial (fusion) enzymes. Airway delivery of protein therapeutics has already been established and should be studied in animal models for active TB.Objective Antimicrobial resistance (AMR) is a major challenge to managing infectious diseases. Africa has the highest incidence of gonorrhoea but there is a lack of comprehensive data from sparse surveillance programs. This study investigated the molecular epidemiology and AMR profiles of Neisseria gonorrhoeae isolates in KwaZulu-Natal province (KZN), South Africa. Methods Repository isolates, from patients attending public healthcare clinics for STI care, were used for phenotypic and genotypic analysis. Etest® was performed to determine antimicrobial susceptibility. Whole-genome sequencing (WGS) was used to determine epidemiology and to predict susceptibility by detecting resistance-associated genes and mutations. Results Among the 61 isolates, multiple sequence types were identified. Six isolates were novel as determined by multilocus sequence typing. N.gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) determined 48 sequence types, of which 35 isolates had novel antimicrobial profiles. Two novel penA alleles and eight novel mtrR alleles were identified. Point mutations were detected in gyrA, parC, mtrR, penA, ponA and porB1. This study revealed a high prevalence of AMR (penicillin 67%, tetracycline 89% and ciprofloxacin 52%). However, spectinomycin, cefixime, ceftriaxone and azithromycin remained 100% effective. Conclusion This study is one of the first to comprehensively describe the epidemiology and AMR of N. selleckchem gonorrhoeae in KZN, South Africa and Africa, using WGS. KZN has a wide strain diversity and most of these sequence types have been detected in multiple countries, however more than half of our isolates have novel antimicrobial profiles. Continued surveillance is crucial to monitor the emergence of resistance to cefixime, ceftriaxone and azithromycin.Acinetobacter baumannii A118, a mostly susceptible strain and AB5075, carbapenem-resistant, were cultured in Lysogeny broth (LB) or LB with different supplements 3.5% human serum albumin (HSA), human serum (HS), meropenem, or meropenem plus 3.5% HSA. Natural transformation levels were enhanced in A. baumannii A118 and AB5075 cultured in medium supplemented with 3.5% HSA. Addition of meropenem plus 3.5% HSA caused synergistic enhancement of natural transformation in A. baumannii A118. Medium containing 3.5% HSA or meropenem enhanced the expression levels of the competence and type IV pilus associated genes. The combination meropenem plus 3.5% HSA produced a synergistic enhancement in the expression levels of many of these genes. The addition of HS, which has a high content of HSA, was also an inducer of these genes. Cultures grown in medium supplemented with HS or 3.5% HSA also affected resistance genes, which were expressed at higher or lower levels depending on the modification required to enhance resistance.
Homepage: https://www.selleckchem.com/products/larotrectinib.html