Synthesis and Biological Evaluation of Novel Carbazole Hybrids as Promising Antimicrobial Agents.

Two series of carbazole analogs of 8-methoxy-N-substituted-9H-carbazole-3-carboxamides (series 1) and carbazolyl substituted rhodanines (series 2) were synthesized through facile synthetic routes. All the final compounds from these two series were evaluated for their preliminary in vitro antifungal and antibacterial activity against four fungal (Candida albicans, Cryptococcus neoformans, Cryptococcus tropicalis and Aspergillus niger) and four bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) strains, respectively. Among the tested compounds, three compounds of series 1 displayed promising antifungal and antibacterial activity, especially against C. neoformans and S. aureus. In addition, one compound of series 1 displayed notable antimicrobial activity (MIC: 6.25 µg/mL) against clinical isolates of C. albicans and C. neoformans (MIC: 12.5 µg/mL). From the second series, four compounds exhibited significant antifungal and antibacterial activity, especially against C. neoformans and S. aureus. The most active compound of series 2 displayed a prominent antimicrobial activity against C. neoformans (MIC: 3.125 µg/mL) and S. aureus (MIC: 1.56 µg/mL), respectively.

Antimicrobial susceptibility of bacterial uropathogens in a South African regional hospital.

Background: Urinary tract infections are common bacterial infections affecting millions worldwide. Although treatment options for urinary tract infections are well established, with ciprofloxacin long considered one of the antibiotics of choice, increasing antibiotic resistance may delay the initiation of appropriate therapy. While this increase in antimicrobial resistance has been demonstrated in multiple studies around the world, there is a dearth of information from developing countries. Objective: This study aimed to describe the antimicrobial susceptibility patterns of commonly isolated bacterial uropathogens in a South African hospital. Methods: Antimicrobial susceptibility data of isolates obtained from urine specimens at the RK Khan Hospital, a regional hospital in KwaZulu-Natal, South Africa, between January 2018 and December 2020 were retrieved from the hospital's laboratory information system and analysed to determine the differences in resistance rates between the most frequently isolated bacterial uropathogens. Results: Of the 3048 bacterial urinary pathogens isolated between 2018 and 2020, Escherichia coli (1603; 53%) was the most common, followed by Klebsiella spp. (437; 14%). Both E. coli and Klebsiella spp. showed high rates of resistance to amoxicillin/clavulanic acid (29.8% and 42.3%) and ciprofloxacin (37.7% and 30.4%). Nitrofurantoin resistance was low among E. coli (6.2%) but high among Klebsiella spp. (61.3%). Conclusion: E. coli and Klebsiella spp. in this study were highly resistant to amoxicillin/clavulanic acid and ciprofloxacin, two of the frequently prescribed oral treatment options. What this study adds: This study highlights the importance of regular local antimicrobial resistance surveillance to inform appropriate empiric therapy.

Cerebellar toxoplasmosis in HIV/AIDS infant: case report and review of the literature.

Cerebellar mass lesion is an uncommon presentation of toxoplasmosis. The authors report one rare case in an 11-month-old HIV/AIDS female infant who presented with deterioration in her developmental milestones. CT scan revealed a ring-enhancing mass lesion in the right cerebellar hemisphere with secondary obstructive hydrocephalus. A ventriculoperitoneal shunt was inserted prior to posterior fossa decompression and biopsy of the lesion. The specimens obtained were divided into two. One specimen was sent for histological diagnosis immediately after surgery while the second specimen was preserved until the release of the histology report. The initial histopathology report indicated a neoplastic process. Immunohistochemical stains were attempted but interpreted with difficulty due to severe tissue necrosis. After waiting for close to 6 weeks without a definite histological diagnosis, the preserved second specimen was sent for histological analysis as a fresh specimen, and reported a diagnosis of toxoplasmosis. This case presented diagnostic challenges to the authors whose radiological impressions of either a neoplastic lesion or a tuberculoma (based on our local neuroepidemiology) were reinforced by intraoperative findings highly suggestive of tuberculoma but which contrasted with the histological report, first as a neoplastic lesion and later toxoplasmosis. Although cerebellar toxoplasmosis is a rare complication of HIV/AIDS, this case report shows that toxoplasmosis should not be overlooked as a differential diagnosis of ring-enhancing cerebellar masses in HIV/AIDS patients irrespective of the patient's age and the absence of constitutional symptoms of toxoplasmosis.

Novel imidazo[2,1-b]-1,3,4-thiadiazoles as promising antifungal agents against clinical isolate of Cryptococcus neoformans.

We herein report the synthesis and in vitro antimicrobial evaluation of twenty five novel hybrid derivatives of imidazo [2,1-b]-1,3,4-thiadiazole containing chalcones (5a-o) and Schiff bases (6a-j) against three fungal strains (Candida albicans, Cryptococcus neoformans and Aspergillus niger). Most of the tested compounds displayed substantial anti-fungal activity with MICs ranging between 1.56 and 100 µg/mL. Compounds 5a, 5b and 5n exhibited promising activity against C. neoformans at a MIC 1.56 µg/mL. In addition, compound 5n also demonstrated significant antifungal activity against the clinical isolates of C. neoformans at MIC 3.125 µg/mL. However, moderate activity was observed for these compounds against four bacterial strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) and Mycobacterium tuberculosis (H37Rv).

Genomics and proteomics of mycobacteriophage patience, an accidental tourist in the Mycobacterium neighborhood.

UNLABELLED: Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host. IMPORTANCE: The mycobacteriophage Patience genome has a notably lower GC content (50.3%) than its Mycobacterium smegmatis host (67.4%) and has markedly different codon usage biases. The viral genome has an abundance of codons that are rare in the host and are decoded by wobble tRNA pairing, although the phage grows well and expression of most of the genes is detected by mass spectrometry. Patience thus has the genomic profile of a virus that evolved primarily in one type of host genetic landscape (moderate-GC bacteria) but has found its way into a distinctly different high-GC environment. Although Patience genes are ill matched to the host expression apparatus, this is of little functional consequence and has not evidently imposed a barrier to migration across the microbial landscape. Interestingly, comparison of expression levels and codon usage profiles reveals evidence of codon selection as the genome evolves and adapts to its new environment.