Yosra I. Nagy

Cairo University

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Diversity and community structure of anaerobic gut fungi in the rumen of wild and domesticated herbivores

Applied and Environmental Microbiology (2024)

Casey H. Meili Moustafa A. TagElDein Adrienne Jones Christina D. Moon Catherine A. Andrews

The rumen houses a diverse community that plays a major role in the digestion process in ruminants. Anaerobic gut fungi (AGF) are key contributors to plant digestion in the rumen. Here, we present a global amplicon-based survey of the rumen AGF mycobiome by examining 206 samples from 15 animal species, 15 countries, and 6 continents. The rumen AGF mycobiome was highly diverse, with 81 out of 88 currently recognized AGF genera or candidate genera identified. However, only six genera (

10.1128/aem.01492-23

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Citations (1)

Position switch of phenylthiazoles: novel compounds with promising anti-MRSA USA300

Medicinal Chemistry Research (2024)

Abdelrahman A. Abuelkhir Mariam Omara Yosra I. Nagy Ahmed Gouda Ahmed S. Attia

10.1007/s00044-024-03243-x

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Tailoring thixotropic mixed-lipid nanoconstructs of voriconazole for the management of Vulvovaginal candidiasis: Formulation, statistical optimization, in vitro characterization and in vivo assessment

Drug Delivery (2021)

Wessam H. Abd-Elsalam Yosra I. Nagy Samar M. Abouelatta

Vulvovaginal candidiasis is a pervasive gynecological condition among women worldwide due to infection recurrence and resistance to conventional drugs. This calls for a novel formulation of alternative medication and with enhanced efficacy. This study aimed to fabricate mixed-lipid nanoconstructs (MLNCs) of voriconazole (VCZ) with a low concentration of lipids applying high shear homogenization and ultrasonication to form a semisolid formulation. Tefose 63 and Gelot 64 were employed as emulsifiers that are specified for vaginal preparations; as per their mucoadhesive properties and their texture enhancing characters, although usually used as lipids in different lipid carriers. A 24 factorial design was established and the optimized formulation was prepared using 10% total lipids, in which solid lipids (Sterotex NF: Glyceryl monostearate) ratio was 1.92:1 and the oils percentage was 30% (Maisine: Glyceryl monooleate, in the ratio of 1:1), and the emulsifiers mixture (Tefose 63: Gelot 64) ratio was 1:1, as 10% of total formulation weight. The optimized formulation with a viscosity of 964.49 ± 57.99 cp showed spherical nanoparticles (322.72 ± 15.11 nm) that entrapped 67.16 ± 3.45% of VCZ and exhibited release of 70.08 ± 2.87% in 8 h. The optimized formulation with high bioadhesive potentials significantly reduced the fungal burden in female Wistar rats infected with vaginal candidiasis, compared to the aqueous VCZ suspension (p < .05). Furthermore, in vivo histopathological findings proved the effectiveness and the safety of the optimized MLNCs formulation after vaginal application. Inclusively, MLNCs formulation could be a promising vaginal delivery system of VCZ for the treatment of vulvovaginal candidiasis.

Sonication

10.1080/10717544.2021.1974608

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Thymol-Loaded Eudragit RS30D Cationic Nanoparticles-Based Hydrogels for Topical Application in Wounds: In Vitro and In Vivo Evaluation

Pharmaceutics (2022)

Amira Mohamed Mohsen Yosra I. Nagy Amr M. Shehabeldine Mona M. Okba

Natural medicines formulated using nanotechnology-based systems are a rich source of new wound-treating therapeutics. This study aims to develop thymol-loaded cationic polymeric nanoparticles (CPNPs) to enhance the skin retention and wound healing efficacy of thymol. The developed materials exhibited entrapment efficiencies of 56.58 to 68.97%, particle sizes of 36.30 to 99.41 nm, and positively charged zeta potential. In Vitro sustained release of thymol up to 24 h was achieved. Selected thymol CPNPs (F5 and C2) were mixed with methylcellulose to form hydrogels (GF5 and GC2). An In Vivo skin-retention study revealed that GF5 and GC2 showed 3.3- and 3.6-fold higher retention than free thymol, respectively. An In Vitro scratch-wound healing assay revealed a significant acceleration in wound closure at 24 h by 58.09% (GF5) and 57.45% (GC2). The potential for free thymol hydrogel, GF5, and GC2 to combat MRSA in a murine skin model was evaluated. The bacterial counts, recovered from skin lesions and the spleen, were assessed. Although a significant reduction in the bacterial counts recovered from the skin lesions was shown by all three formulations, only GF5 and GC2 were able to reduce the bacterial dissemination to the spleen. Thus, our study suggests that Eudragit RS30D nanoparticles-based hydrogels are a potential delivery system for enhancing thymol skin retention and wound healing activity.

Thymol

Zeta potential

Cationic polymerization

10.3390/pharmaceutics15010019

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Restoring vancomycin activity against resistant Enterococcus faecalis using a transcription factor decoy as a vanA operon-inhibitor

Journal of Antimicrobial Chemotherapy (2024)

Loai M Abdelall Yosra I. Nagy Mona T. Kashef

Abstract Background Vancomycin-resistant enterococci (VRE) represent a public health threat due to the few available treatments. Such alarm has triggered worldwide initiatives to develop effective antimicrobial compounds and novel delivery and therapeutic strategies. vanA operon is responsible for most cases of acquired vancomycin resistance in enterococci. Objectives Development of a transcription factor decoy (TFD) system as a vanA gene transcription-inhibitor. Methods Vancomycin MIC was determined in the presence of TFD-lipoplexes. Additionally, the effect of TFD-lipoplexes on the expression level of the vanA gene and the growth pattern of E. faecalis was evaluated. The haemolytic activity of the developed TFD-lipoplexes and their cytotoxicity were examined. TFD-lipoplexes efficiency in treating vancomycin-resistant E. faecalis (VREF) infection was tested in vivo using a systemic mice infection model. Results A reduction in vancomycin MIC against VRE from 256 mg/L (resistant) to 16 mg/L (intermediate susceptible), in the presence of TFD-lipoplexes, was recorded. The developed TFD-lipoplexes lacked any effect on E. faecalis growth and significantly reduced the transcription level of the vanA gene by about 3-fold. In an initial evaluation of the safety of TFD-lipoplexes, they were found not to be overtly haemolytic to human blood or cytotoxic to human skin fibroblast cells. The co-administration of TFD-lipoplexes and vancomycin efficiently eradicated VREF infection in vivo. Conclusions The developed TFD-lipoplexes successfully restored vancomycin activity against VREF. They offer a safe effective unconventional therapy against this stubborn organism and present a revolution in gene therapy that can be applied to other resistance-encoding genes in various organisms.

Enterococcus faecalis

10.1093/jac/dkae320

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Rifaximin microbial resistance and its efficacy and safety as a secondary prophylaxis of hepatic encephalopathy in patients with hepatitis C virus‐related cirrhosis

International Journal of Clinical Practice (2021)

Mai Abdel Moneim Doaa H. Abdelaziz Yosra I. Nagy Amin Abdel Baki Ahmed S. Attia

Background and aim Rifaximin is an oral antibiotic with promising efficacy in the reduction of hepatic encephalopathy (HE) recurrence. Development of microbial resistance to rifaximin is not studied yet in HE. The study aim was to assess the microbial resistance, safety and efficacy of rifaximin as secondary prophylaxis of HE. Method In this open-label parallel, prospective interventional study, 100 patients were randomly allocated either to receive 400 mg rifaximin 3 times/d plus 30-45 mL lactulose 3 times/d (intervention group) or to receive the standard of care only which is lactulose alone (control group) for 6 months. The primary outcome of the study was the difference between minimum inhibitory concentration (MIC) of rifaximin among the two studied groups at the end of treatment. The secondary outcomes included the time to first episode of HE, time to first hospitalisation, and patient's survival. Results The MIC did not differ significantly after treatment exposure compared with baseline either between groups or within the same group. The time to new episode of HE was 18.84 ± 6.49 weeks (mean ± SD) in the intervention group and was significantly longer (P = .002) than that in the control group 14 ± 7.52 weeks. Moreover, only 23 (46%) patients developed overt HE in the intervention group compared with 35 patients (70%) in the control group (P = .005). Also, there was an observed 32% reduction in the risk of hospitalisation in intervention group compared with control group. Conclusion Rifaximin succeeded to maintain remission from new episodes of HE in hepatitis C virus cirrhotic patients with limited potential for development of microbial resistance over the study period. ClinicalTrials.gov Identifier: NCT04736836.

Rifaximin

Lactulose

Hepatic Encephalopathy

10.1111/ijcp.14807

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Small Molecule Alkynyl‐Phenylaminoguanidines: A New Weapon Against Multi‐Drug Resistant Bacteria

ChemistrySelect (2025)

Abdelrahman A. Abuelkhir Yosra I. Nagy Tarek Gamal Ahmed Abdelhalim Ahmed S. Attia

Abstract The coexistence of Gram‐negative organisms, such as Acinetobacter baumannii and methicillin‐resistant Staphylococcus aureus (MRSA) in diabetic foot ulcers poses significant therapeutic challenges and increases the rate of treatment failure. By studying the structure‐activity relationships of small alkynylphenyl‐aminoguanidine molecules, we identified heptyne and octyne derivatives as promising antibacterial agents. These compounds exhibited potent activity against Gram‐positive MRSA USA300 (MIC = 0.5 µg/mL) and reasonable activity against Gram‐negative A. baumannii AB5075 (MIC = 8 µg/mL). It is noteworthy that octynylphenyl‐aminoguanidine demonstrated a rapid bactericidal effect within 2 h and showed no evidence of resistance development. Despite systemic intolerance, topical application of the two most active compounds significantly improved skin condition and reduced bacterial burdens in an murine skin infection model (MRSA). These results highlight a promising therapeutic avenue for MRSA skin infections, with potential efficacy in coinfections with multidrug‐resistant Gram‐negative pathogens such as A. baumannii .

10.1002/slct.202404320

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Patterns and determinants of the global herbivorous mycobiome

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Casey H. Meili Adrienne Jones Alex X. Arreola Jeffrey Habel Carrie J. Pratt

Abstract In spite of their indispensable role in host nutrition, the anaerobic gut fungal (AGF) component of the herbivorous gut microbiome remains poorly characterized. To examine global patterns and determinants of AGF diversity, we generated and analyzed an amplicon dataset from 661 fecal samples from 34 animal species, 9 families, and 6 continents. We identified 56 novel genera, greatly expanding AGF diversity beyond current estimates. Both stochastic (homogenizing dispersal and drift) and deterministic (homogenizing selection) processes played an integral role in shaping AGF communities, with a higher level of stochasticity observed in foregut fermenters. Community structure analysis revealed a distinct pattern of phylosymbiosis, where host-associated (animal species, family, and gut type), rather than ecological (domestication status and biogeography) factors predominantly shaped the community. Hindgut fermenters exhibited stronger and more specific fungal-host associations, compared to broader mostly non-host specific associations in foregut fermenters. Transcriptomics-enabled phylogenomic and molecular clock analyses of 52 strains from 14 genera indicated that most genera with preferences for hindgut hosts evolved earlier (44-58 Mya), while those with preferences for foregut hosts evolved more recently (22-32 Mya). This pattern is in agreement with the sole dependence of herbivores on hindgut fermentation past the Cretaceous-Paleogene (K-Pg) extinction event through the Paleocene and Eocene, and the later rapid evolution of animals employing foregut fermentation strategy during the early Miocene. Only a few AGF genera deviated from this pattern of co-evolutionary phylosymbiosis, by exhibiting preferences suggestive of post-evolutionary environmental filtering. Our results greatly expand the documented scope of AGF diversity and provide an ecologically and evolutionary-grounded model to explain the observed patterns of AGF diversity in extant animal hosts.

Foregut

Hindgut

10.1101/2022.11.21.517404

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Isogenic mutations in the Moraxella catarrhalis CydDC system display pleiotropic phenotypes and reveal the role of a palindrome sequence in its transcriptional regulation

Microbiological Research (2017)

Yosra I. Nagy Manal M. M. Hussein Yasser Ragab Ahmed S. Attia

Moraxella (Branhamella) catarrhalis

10.1016/j.micres.2017.06.002

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Acinetobacter baumannii, Klebsiella pneumoniae and Elizabethkingia miricola isolated from wastewater have biodegradable activity against fluoroquinolone

World Journal of Microbiology and Biotechnology (2022)

Reham Alaa Eldin Shaker Yosra I. Nagy Mina E. Adly Rania Abdelmonem Khattab Yasser Ragab

Ciprofloxacin (CIP) and levofloxacin (LEV), widely used fluoroquinolone antibiotics, are often found in sewage from the sewage treatment plants and marine environment. In this study, CIP and LEV biodegrading bacterial consortia were obtained from industrial wastewater. Microorganisms in these consortia were identified as Acinetobacter baumannii (A. baumannii), Klebsiella pneumoniae (K. pneumoniae) and Elizabethkingia miricola (E. miricola). The impacts of the critical operating parameters on the elimination of CIP and LEV by bacterial consortia have been investigated and optimized to achieve the maximum levels of CIP and LEV biodegradation. Using liquid chromatography with tandem mass spectrometry (LC-MS-MS), possible degradation pathways for CIP and LEV were suggested by analyzing the intermediate degradation products. The role of the enzymes fluoroquinolone-acetylating aminoglycoside (6'-N-acetyltransferase) and cytochrome P450 (CYP450) in the breakdown of fluoroquinolones (FQs) was investigated as well. According to our findings, various biodegradation mechanisms have been suggested, including cleavage of piperazine ring, substitution of F atom, hydroxylation, decarboxylation, and acetylation, as the main biotransformation reactions. This study discovers the ability of non-reported bacterial strains to biodegrade both CIP and LEV as a sole carbon source, providing new insights into the biodegradation of CIP and LEV.

Acinetobacter baumannii

Biotransformation

10.1007/s11274-022-03367-5

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Citations (13)