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Insights into complex nanopillar-bacteria interactions: Roles of nanotopography and bacterial surface proteins

Ishak MI, Jenkins J, Kulkarni S, Keller TF, Briscoe WH, Nobbs AH, et al.

J Colloid Interface Sci, 2021 Dec 15;604:91-103.
PMID: 34265695 DOI: 10.1016/j.jcis.2021.06.173

Nanopillared surfaces have emerged as a promising strategy to combat bacterial infections on medical devices. However, the mechanisms that underpin nanopillar-induced rupture of the bacterial cell membrane remain speculative. In this study, we have tested three medically relevant poly(ethylene terephthalate) (PET) nanopillared-surfaces with well-defined nanotopographies against both Gram-negative and Gram-positive bacteria. Focused ion beam scanning electron microscopy (FIB-SEM) and contact mechanics analysis were utilised to understand the nanobiophysical response of the bacterial cell envelope to a single nanopillar. Given their importance to bacterial adhesion, the contribution of bacterial surface proteins to nanotopography-mediated cell envelope damage was also investigated. We found that, whilst cell envelope deformation was affected by the nanopillar tip diameter, the nanopillar density affected bacterial metabolic activities. Moreover, three different types of bacterial cell envelope deformation were observed upon contact of bacteria with the nanopillared surfaces. These were attributed to bacterial responses to cell wall stresses resulting from the high intrinsic pressure caused by the engagement of nanopillars by bacterial surface proteins. Such influences of bacterial surface proteins on the antibacterial action of nanopillars have not been previously reported. Our findings will be valuable to the improved design and fabrication of effective antibacterial surfaces.
Fulltext Comparison of diagnostic algorithms in clinically suspected viral myocarditis: Agreement between cardiovascular magnetic resonance, endomyocardial biopsy, and troponin T

Zainal H, Rolf A, Zhou H, Vasquez M, Escher F, Keller T, et al.

J Cardiovasc Magn Reson, 2024 08 25;26(2):101087.
PMID: 39191369 DOI: 10.1016/j.jocmr.2024.101087

AIMS: Myocardial inflammation is increasingly detected noninvasively by tissue mapping with cardiovascular magnetic resonance (CMR). Intraindividual agreement with endomyocardial biopsy (EMB) or markers of myocardial injury, high-sensitive cardiac troponin (hs-cTnT) in patients with clinically suspected viral myocarditis is incompletely understood.
METHODS: Prospective multicenter study of consecutive patients with clinically suspected myocarditis who underwent blood testing for hs-cTnT, CMR, and EMB as a part of diagnostic workup. EMB was considered positive based on immunohistological criteria in line with the European Society of Cardiology (ESC) definitions. CMR diagnoses employed tissue mapping using sequence-specific cut-off for native T1 and T2 mapping; active inflammation was defined as T1 ≥2 standard deviation (SD) and T2 ≥2 SD above the mean of normal range. Hs-cTnT of greater than 13.9 ng/L was considered significant.
RESULTS: A total of 114 patients (age (mean ± SD) 54 ± 16, 65% males) were included, of which 79 (69%) had positive EMB criteria, 64 (56%) CMR criteria, and a total of 58 (51%) positive troponin. Agreement between EMB and CMR diagnostic criteria was poor (CMR vs ESC: area under the curve (AUC): 0.51 (0.39-0.62)). The agreement between a significant hs-cTnT rise and CMR-based diagnosis of myocarditis was good (AUC: 0.84 (0.68-0.92); p
Fulltext Native T1 and T2 provide distinctive signatures in hypertrophic cardiac conditions - Comparison of uremic, hypertensive and hypertrophic cardiomyopathy

Arcari L, Hinojar R, Engel J, Freiwald T, Platschek S, Zainal H, et al.

Int J Cardiol, 2020 05 01;306:102-108.
PMID: 32169347 DOI: 10.1016/j.ijcard.2020.03.002

AIMS: Profound left ventricular (LV) hypertrophy with diastolic dysfunction and heart failure is the cardinal manifestation of heart remodelling in chronic kidney disease (CKD). Previous studies related increased T1 mapping values in CKD with diffuse fibrosis. Native T1 is a non-specific readout that may also relate to increased intramyocardial fluid. We examined concomitant T1 and T2 mapping signatures and undertook comparisons with other hypertrophic conditions.
METHODS: In this prospective multicentre study, consecutive CKD patients (n = 154) undergoing routine clinical cardiac magnetic resonance (CMR) imaging were compared with patients with hypertensive (HTN, n = 163) and hypertrophic cardiomyopathy (HCM, n = 158), and normotensive controls (n = 133).
RESULTS: Native T1 was significantly higher in all patient groups, whereas native T2 in CKD only (p 
Fulltext Structure of the Reductase Domain of a Fungal Carboxylic Acid Reductase and Its Substrate Scope in Thioester and Aldehyde Reduction

Daniel B, Hashem C, Leithold M, Sagmeister T, Tripp A, Stolterfoht-Stock H, et al.

ACS Catal, 2022 Dec 16;12(24):15668-15674.
PMID: 37180375 DOI: 10.1021/acscatal.2c04426

The synthesis of aldehydes from carboxylic acids has long been a challenge in chemistry. In contrast to the harsh chemically driven reduction, enzymes such as carboxylic acid reductases (CARs) are considered appealing biocatalysts for aldehyde production. Although structures of single- and didomains of microbial CARs have been reported, to date no full-length protein structure has been elucidated. In this study, we aimed to obtain structural and functional information regarding the reductase (R) domain of a CAR from the fungus Neurospora crassa (Nc). The NcCAR R-domain revealed activity for N-acetylcysteamine thioester (S-(2-acetamidoethyl) benzothioate), which mimics the phosphopantetheinylacyl-intermediate and can be anticipated as the minimal substrate for thioester reduction by CARs. The determined crystal structure of the NcCAR R-domain reveals a tunnel that putatively harbors the phosphopantetheinylacyl-intermediate, which is in good agreement with docking experiments performed with the minimal substrate. In vitro studies were performed with this highly purified R-domain and NADPH, demonstrating carbonyl reduction activity. The R-domain was able to accept not only a simple aromatic ketone but also benzaldehyde and octanal, which are typically considered to be the final product of carboxylic acid reduction by CAR. Also, the full-length NcCAR reduced aldehydes to primary alcohols. In conclusion, aldehyde overreduction can no longer be attributed exclusively to the host background.