Noha M. Elhosseiny

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The Moraxella catarrhalis AdhC–FghA system is important for formaldehyde detoxification and protection against pulmonary clearance

Medical Microbiology and Immunology (2024)

Dina Othman Noha M. Elhosseiny Wafaa N. Eltayeb Ahmed S. Attia

Abstract Multidrug-resistant clinical isolates of Moraxella catarrhalis have emerged, increasing the demand for the identification of new treatment and prevention strategies. A thorough understanding of how M. catarrhalis can establish an infection and respond to different stressors encountered in the host is crucial for new drug-target identification. Formaldehyde is a highly cytotoxic compound that can be produced endogenously as a by-product of metabolism and exogenously from environmental sources. Pathways responsible for formaldehyde detoxification are thus essential and are found in all domains of life. The current work investigated the role of the system consisting of the S -hydroxymethyl alcohol dehydrogenase (AdhC), a Zn-dependent class III alcohol dehydrogenase , and the S -formyl glutathione hydrolase (FghA) in the formaldehyde detoxification process in M. catarrhalis . Bioinformatics showed that the components of the system are conserved across the species and are highly similar to those of Streptococcus pneumoniae , which share the same biological niche. Isogenic mutants were constructed to study the function of the system in M. catarrhalis . A single fghA knockout mutant did not confer sensitivity to formaldehyde, while the adhC–fghA double mutant is formaldehyde-sensitive. In addition, both mutants were significantly cleared in a murine pulmonary model of infection as compared to the wild type, demonstrating the system’s importance for this pathogen’s virulence. The respective phenotypes were reversed upon the genetic complementation of the mutants. To date, this is the first study investigating the role of the AdhC–FghA system in formaldehyde detoxification and pathogenesis of M. catarrhalis .

Formaldehyde dehydrogenase

Detoxification

Moraxella (Branhamella) catarrhalis

10.1007/s00430-024-00785-0

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The effect of α1-antitrypsin deficiency combined with increased bacterial loads on chronic obstructive pulmonary disease pharmacotherapy: A prospective, parallel, controlled pilot study

Journal of Advanced Research (2016)

Marwa G. Hennawy Noha M. Elhosseiny Hussein Sultan Wael Abdelfattah Yousry Akl

Chronic obstructive pulmonary disease (COPD) is caused by α1-antitrypsin deficiency (AATD) genetic susceptibility and exacerbated by infection. The current pilot study aimed at studying the combined effect of AATD and bacterial loads on the efficacy of COPD conventional pharmacotherapy. Fifty-nine subjects (29 controls and 30 COPD patients) were tested for genetic AATD and respiratory function. The bacterial loads were determined to the patients' group who were then given a long acting beta-agonist and corticosteroid inhaler for 6 months. Nineteen percent of the studied group were Pi∗MZ (heterozygote deficiency variant), Pi∗S (5%) (milder deficiency variant), Pi∗ZZ (10%) (the most common deficiency variant), and Pi∗Mmalton (2%) (very rare deficiency variant). The patients' sputum contained from 0 to 8 × 108 CFU/mL pathogenic bacteria. The forced vital capacity (FVC6) values of the AAT non-deficient group significantly improved after 3 and 6 months. Patients lacking AATD and pathogenic bacteria showed significant improvement in forced expiratory volume (FEV1), FEV1/FVC6, FVC6, and 6 min walk distance (6MWD) after 6 months. However, patients with AATD and pathogenic bacteria showed only significant improvement in FEV1 and FEV1/FVC6. The findings of this pilot study highlight for the first time the role of the combined AATD and pathogenic bacterial loads on the efficacy of COPD treatment.

Pharmacotherapy

Alpha 1-antitrypsin deficiency

Sputum culture

10.1016/j.jare.2016.05.002

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Citations (4)

Comparative proteomics analyses of Acinetobacter baumannii strains ATCC 17978 and AB5075 reveal the differential role of type II secretion system secretomes in lung colonization and ciprofloxacin resistance

Microbial Pathogenesis (2018)

Noha M. Elhosseiny Nada B Elhezawy Ahmed S. Attia

Acinetobacter baumannii

10.1016/j.micpath.2018.12.039

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Citations (28)

Demographic Analysis Of 90 Polycythemia Vera Egyptian Cases : An Egyptian Reference Center Experience

Blood (2013)

Mervat Mattar Nihad Tawfik Noha M. Elhosseiny Mohamed Abdelkader Morad

Portal vein thrombosis

10.1182/blood.v122.21.5245.5245

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Association Between Combined Presence of Hepatitis C Virus and Polymorphisms in Different Genes With Toxicities of Methotrexate and 6‐Mercaptopurine in Children With Acute Lymphoblastic Leukemia

Pediatric Blood & Cancer (2016)

Doaa H. Abdelaziz Noha M. Elhosseiny Sahar A. Khaleel Nirmeen A. Sabry Ahmed S. Attia

The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL).One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records.There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (P < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation was observed (P values <0.001, 0.02, and 0.001, respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases.The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens.

Thiopurine methyltransferase

Mercaptopurine

10.1002/pbc.26045

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Citations (7)

Exploring the antimicrobial activity of Origanum majorana L. against the highly virulent multidrug-resistant Acinetobacter baumannii AB5075: UPLC-HRMS profiling with in vitro and in silico studies

Future Journal of Pharmaceutical Sciences (2024)

Norhan H. Mahdally Abdalla E. M. Salih Riham A. El‐Shiekh Ahmed M. Sayed Noha M. Elhosseiny

Abstract Background The infamous multidrug-resistant (MDR) bacterium Acinetobacter baumannii is becoming a nightmare in intensive care units across the globe. Since there are now very few effective antimicrobial agents, it is necessary to explore unconventional resources for novel antimicrobials. This study investigated the potential antimicrobial activity of Origanum majorana L. against A. baumannii employing multiple approaches including antimicrobial susceptibility, fractionation, ultra-performance liquid chromatography–high-resolution mass spectrometry (UPLC-HRMS) dereplication, and in silico analysis for target/ligand identification. Results On the extremely pathogenic MDR strain A. baumannii AB5075, O. majorana L. has shown a significant growth inhibitory effect (MIC = 0.675 mg/mL). The polar 50% methanol fraction was the most active (MIC = 0.5 mg/mL). The UPLC-HRMS dereplication of the bioactive fraction detected 29 metabolites belonging to different chemical classes. Justicidin B, one of the identified metabolites, was projected by preliminary in silico analysis to be the most highly scoring metabolite for binding with molecular targets in A. baumannii with a Fit score = 8.56 for enoyl-ACP reductase (FabI) (PDB ID: 6AHE), suggesting it to be its potential target. Additionally, docking, molecular dynamics simulation, and bioinformatics analysis suggested that this interaction is similar to a well-known FabI inhibitor. The amino acids involved in the interaction are conserved among different MDR A. baumannii strains and the effectiveness could extend to Gram-negative pathogens within the ESKAPE group. Conclusions Origanum majorana L. extract exhibits antimicrobial activity against A. baumannii using one or more metabolites in its 50% methanol fraction. The characterized active metabolite is hypothesized to be justicidin B which inhibits the growth of A. baumannii AB5075 via targeting its fatty acid synthesis.

Acinetobacter baumannii

Origanum

Checkerboard

10.1186/s43094-024-00641-1

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Citations (3)

γ-Glutamyltransferase as a Novel Virulence Factor of Acinetobacter baumannii Inducing Alveolar Wall Destruction and Renal Damage in Systemic Disease

The Journal of Infectious Diseases (2020)

Noha M. Elhosseiny Nada B Elhezawy R. M. Sayed Marwa S. Khattab Miran Y El Far

Abstract A thorough understanding of Acinetobacter baumannii pathogenicity is the key to identifying novel drug targets. In the current study, we characterize the γ-glutamyltransferase enzyme (GGT) as a novel virulence factor. A GGT assay showed that the enzyme is secreted via the type II secretion system and results in higher extracellular activity for the hypervirulent AB5075 than the laboratory-adapted strain American Type Culture Collection 17978. Enzyme-linked immunosorbent assay revealed that the former secretes larger amounts of GGT, and a rifampicin messenger RNA stability study showed that one reason for this could be the longer AB5075 ggt transcript half-life. Infection models confirmed that GGT is required for the virulence of A. baumannii. Finally, we show that clinical isolates with significantly higher extracellular GGT activity resulted in more severe infections, and assay of immune response and tissue damage markers confirm this correlation. The current findings establish for the first time the role of the GGT in the pathogenicity of A. baumannii.

Acinetobacter baumannii

Virulence factor

10.1093/infdis/jiaa262

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Citations (8)

A Rapid Lysostaphin Production Approach and a Convenient Novel Lysostaphin Loaded Nano-emulgel; As a Sustainable Low-Cost Methicillin-Resistant Staphylococcus aureus Combating Platform

Biomolecules (2020)

Hanzada T. Nour El‐Din Noha M. Elhosseiny Mohamed A. El-Gendy Azza A. Mahmoud Manal M. M. Hussein

Staphylococcus aureus is a Gram-positive pathogen that is capable of infecting almost every organ in the human body. Alarmingly, the rapid emergence of methicillin-resistant S. aureus strains (MRSA) jeopardizes the available treatment options. Herein, we propose sustainable, low-cost production of recombinant lysostaphin (rLST), which is a native bacteriocin destroying the staphylococcal cell wall through its endopeptidase activity. We combined the use of E. coli BL21(DE3)/pET15b, factorial design, and simple Ni-NTA affinity chromatography to optimize rLST production. The enzyme yield was up to 50 mg/L culture, surpassing reported systems. Our rLST demonstrated superlative biofilm combating ability by inhibiting staphylococcal biofilms formation and detachment of already formed biofilms, compared to vancomycin and linezolid. Furthermore, we aimed at developing a novel rLST topical formula targeting staphylococcal skin infections. The phase inversion composition (PIC) method fulfilled this aim with its simple preparatory steps and affordable components. LST nano-emulgel (LNEG) was able to extend active LST release up to 8 h and cure skin infections in a murine skin model. We are introducing a rapid, convenient rLST production platform with an outcome of pure, active rLST incorporated into an effective LNEG formula with scaling-up potential to satisfy the needs of both research and therapeutic purposes.

Lysostaphin

10.3390/biom10030435

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Citations (15)

The secretome of Acinetobacter baumannii ATCC 17978 type II secretion system reveals a novel plasmid encoded phospholipase that could be implicated in lung colonization

International Journal of Medical Microbiology (2016)

Noha M. Elhosseiny O. M. El‐Tayeb Aymen S. Yassin Stephen Lory Ahmed S. Attia

Acinetobacter baumannii

10.1016/j.ijmm.2016.09.006

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Citations (25)

Development and validation of LC–MS/MS assay for the simultaneous determination of methotrexate, 6-mercaptopurine and its active metabolite 6-thioguanine in plasma of children with acute lymphoblastic leukemia: Correlation with genetic polymorphism