De Novo Access to BODIPY C-Glycosides as Linker-Free Nonsymmetrical BODIPY-Carbohydrate Conjugates.

Recent years have witnessed an increasing interest in the synthesis and study of BODIPY-glycoconjugates. Most of the described synthetic methods toward these derivatives involve postfunctional modifications of the BODIPY core followed by the covalent attachment of the fluorophore and the carbohydrate through a "connector". Conversely, few de novo synthetic approaches to linker-free carbohydrate-BODIPY hybrids have been described. We have developed a reliable modular, de novo, synthetic strategy to linker-free BODIPY-sugar derivatives using the condensation of pyrrole C-glycosides with a pyrrole-carbaldehyde derivative mediated by POCl3. This methodology allows labeling of carbohydrate biomolecules with fluorescent-enough BODIPYs within the biological window, stable in aqueous media, and able to display singlet oxygen generation.

Linkers in fragment-based drug design: an overview of the literature.

INTRODUCTION: In fragment-based drug design, fragment linking is a popular strategy where two fragments binding to different sub-pockets of a target are linked together. This attractive method remains challenging especially due to the design of ideal linkers. AREAS COVERED: The authors review the types of linkers and chemical reactions commonly used to the synthesis of linkers, including those utilized in protein-templated fragment self-assembly, where fragments are directly linked in the presence of the protein. Finally, they detail computational workflows and software including generative models that have been developed for fragment linking. EXPERT OPINION: The authors believe that fragment linking offers key advantages for compound design, particularly for the design of bivalent inhibitors linking two distinct pockets of the same or different subunits. On the other hand, more studies are needed to increase the potential of protein-templated approaches in FBDD. Important computational tools such as structure-based de novo software are emerging to select suitable linkers. Fragment linking will undoubtedly benefit from developments in computational approaches and machine learning models.

Prevalence of Staphylococcus aureus and methicillin-resistant S aureus on environmental surfaces in Ohio nursing homes.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is common in medical institutions. We sought to examine the prevalence of S aureus on environmental surfaces in nursing homes and to obtain molecular information on contaminating strains. METHODS: A total of 259 environmental samples were collected from 7 different nursing homes in Northeast Ohio (NEO), from suburban, urban, and rural settings. The presence of the mecA and PVL genes was determined, and spa typing was performed in order to identify molecular types. RESULTS: The prevalence of S aureus was 28.6% (74/259). The prevalence of MRSA and methicillin-susceptible S aureus was 20.1% (52/259) and 8.5% (22/259), respectively. S aureus contamination in suburban, urban, and rural sites was 25.7% (38/148), 45.9% (34/74), and 5.4% (2/37), respectively. MRSA was detected in 16.9% (25/148) of suburban samples and 36.5% (27/74) of urban samples. No MRSA was found in rural samples. Nursing homes from urban areas had a significantly higher (P < .001) prevalence of S aureus compared to nursing homes from suburban and rural sites. Areas with high nurse touch rates were the most commonly contaminated. CONCLUSIONS: We found differences in the prevalence of S aureus and MRSA in nursing homes in different regions of NEO. Part of these differences may result from transfers from hospitals; the urban nursing homes had 4 to 15 hospitals nearby, whereas suburban and rural locations had 1 to 3 hospitals within the area.

Characterization of Staphylococcus aureus in Goose Feces from State Parks in Northeast Ohio.

Staphylococcus aureus can colonize a range of species. Although numerous studies have isolated pathogenic bacteria from wild birds, very little is known regarding S. aureus and their potential to spread methicillin-resistant (MRSA) strains. The objective of this study was to determine the presence and molecular characteristics of S. aureus in geese fecal samples collected from ten state parks across Northeast Ohio (NEO). A total of 182 fecal samples from Canada geese (Branta canadensis) were collected in April 2015. Isolates were characterized using multi-locus sequence (MLST) and spa typing, as well as PCR to detect the presence of Panton-Valentine leukocidin (PVL), mecA, and scn genes. Antibiotic susceptibility testing was done via Vitek-2 system. The overall contamination by S. aureus in fecal samples was 7.1% (13/182); 7/182 (3.8%) were MRSA and 6/182 (3.3%) were methicillin-susceptible S. aureus (MSSA). One isolate was positive for PVL. A total of eight different spa types were observed. MLST included ST5, ST8, ST291, ST298, and ST2111. One (7.7%) MSSA isolate was multi-drug resistant. The S. aureus contamination in NEO state parks ranged from 0% (park 1, 4, 8, 9) to 35% (7/20) (park 5). Parks 2, 3, 6, and 7 had 5% (1/20) positive. The results of this study indicate that the feces of geese collected at various state parks in NEO may harbor S. aureus.

Prevalence and Characterization of Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus on Public Recreational Beaches in Northeast Ohio.

Staphylococcus aureus can cause severe life-threatening illnesses such as sepsis and endocarditis. Although S. aureus has been isolated from marine water and intertidal beach sand, only a few studies have been conducted to assess prevalence of S. aureus at freshwater recreational beaches. As such, we aimed to determine prevalence and molecular characteristics of S. aureus in water and sand at 10 freshwater recreational beaches in Northeast Ohio, USA. Samples were analyzed using standard microbiology methods, and resulting isolates were typed by spa typing and multilocus sequence typing. The overall prevalence of S. aureus in sand and water samples was 22.8% (64/280). The prevalence of methicillin-resistant S. aureus (MRSA) was 8.2% (23/280). The highest prevalence was observed in summer (45.8%; 55/120) compared to fall (4.2%; 5/120) and spring (10.0%; 4/40). The overall prevalence of Panton-Valentine leukocidin genes among S. aureus isolates was 21.4% (15/70), and 27 different spa types were identified. The results of this study indicate that beach sand and freshwater of Northeast Ohio were contaminated with S. aureus, including MRSA. The high prevalence of S. aureus in summer months and presence of human-associated strains may indicate the possibility of role of human activity in S. aureus contamination of beach water and sand. While there are several possible routes for S. aureus contamination, S. aureus prevalence was higher in sites with wastewater treatment plants proximal to the beaches.

Prospective multicenter surveillance identifies Staphylococcus aureus infections caused by livestock-associated strains in an agricultural state.

We conducted a surveillance study to investigate the epidemiology of Staphylococcus aureus infections in Iowa, using a convenience sample. Diagnostic laboratories submitted 20 S. aureus isolates per month for a 20-month period between 2011 and 2013. Of the 2226 isolates analyzed, 73.6% were methicillin-resistant S. aureus (MRSA) and 26.4% were methicillin-susceptible S. aureus (MSSA). S. aureus infections in 25 patients (1%) were caused by ST398- and ST9-associated strain types, and appeared to be a common occurrence in areas of the state with the highest numbers of hogs and hog farms. Twenty nine (5.1%) of MSSA isolates and 10 (40.0%) livestock-associated strains were multi-drug resistant.