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Article ; Online: Computational modeling and druggability assessment of Aggregatibacter actinomycetemcomitans leukotoxin.

Hakmi, Mohammed / Bouricha, El Mehdi / El Harti, Jaouad / Amzazi, Said / Belyamani, Lahcen / Khanfri, Jamal Eddine / Ibrahimi, Azeddine

Computer methods and programs in biomedicine

2022 Volume 222, Page(s) 106952

Abstract: The leukotoxin (LtxA) of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is a protein exotoxin belonging to the repeat-in-toxin family (RTX). Numerous studies have demonstrated that LtxA may play a critical role in the pathogenicity of A. ...

Abstract	The leukotoxin (LtxA) of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is a protein exotoxin belonging to the repeat-in-toxin family (RTX). Numerous studies have demonstrated that LtxA may play a critical role in the pathogenicity of A. actinomycetemcomitans since hyper-leukotoxic strains have been associated with severe disease. Accordingly, considerable effort has been made to elucidate the mechanisms by which LtxA interacts with host cells and induce their death. However, these attempts have been hampered by the unavailability of a tertiary structure of the toxin, which limits the understanding of its molecular properties and mechanisms. In this paper, we used homology and template free modeling algorithms to build the complete tertiary model of LtxA at atomic level in its calcium-bound Holo-state. The resulting model was refined by energy minimization, validated by Molprobity and ProSA tools, and subsequently subjected to a cumulative 600ns of all-atom classical molecular dynamics simulation to evaluate its structural aspects. The druggability of the proposed model was assessed using Fpocket and FTMap tools, resulting in the identification of four putative cavities and fifteen binding hotspots that could be targeted by rational drug design tools to find new ligands to inhibit LtxA activity.
MeSH term(s)	Aggregatibacter actinomycetemcomitans/chemistry ; Aggregatibacter actinomycetemcomitans/metabolism ; Computer Simulation ; Exotoxins/chemistry ; Exotoxins/metabolism ; Exotoxins/pharmacology
Chemical Substances	Exotoxins ; leukotoxin
Language	English
Publishing date	2022-06-13
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632564-6
ISSN	1872-7565 ; 0169-2607
ISSN (online)	1872-7565
ISSN	0169-2607
DOI	10.1016/j.cmpb.2022.106952
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Article ; Online: Assessment of the HBV vaccine response in a group of HIV-infected children in Morocco.

Haban, Houda / Benchekroun, Soumia / Sadeq, Mina / Benjouad, Abdelaziz / Amzazi, Said / Oumzil, Hicham / Elharti, Elmir

BMC public health

2017 Volume 17, Issue 1, Page(s) 752

Abstract: Background: Since its development in the early 1980s, Hepatitis B virus (HBV) vaccine has been proven to be highly protective. However, its immunogenicity may be ineffective among HIV-infected children. In Morocco, HBV vaccine was introduced in 1999, ... ...

Abstract	Background: Since its development in the early 1980s, Hepatitis B virus (HBV) vaccine has been proven to be highly protective. However, its immunogenicity may be ineffective among HIV-infected children. In Morocco, HBV vaccine was introduced in 1999, and since then all infants, including vertically HIV-infected infants, have been following the vaccination schedule, implemented by the Moroccan ministry of health. An assessment of the immunization of these children is important to optimize efforts aimed at tackling Hepatitis B coinfection, within the country. Methods: Forty-nine HIV-infected children (HIV group) and 112 HIV uninfected children (control group) were enrolled in this study. Samples were tested by Elisa (Monolisa Anti-HBs, Biorad) to quantify the anti-HBs antibodies. The % of lymphocyte subsets i.e. CD4+ T cells, CD8+ T cells, B cells, and NK, was determined by flow cytometry, using CellQuest Pro software (Becton-Dickinson), and for HIV group, HIV viral load was measured by real time PCR assay (Abbott). All variables were statistically compared in the two groups. Results: The median age was 51 ± 35 months for the HIV group and 50 ± 36 months (p > 0.05) for the control group. Female represented 63% and 41% (p = 0.01), among the HIV group and the control group, respectively. Among HIV-infected children, 71.4% (35/49) were under HAART therapy at the enrollment in the study. Seroprotection titer i.e. anti-HBs ≥10mUI/ml among control group was 76% (85/112), and only 29% (14/49) among the perinatally HIV-infected children (p < 0.0001). Lower % of CD4 + T cells was observed in HIV-infected children with a poor anti-HBs response. Conclusion: In this studied group, we have shown that despite the vaccination of HIV-children with HBV vaccine, 71% did not show any seroprotective response. These findings support the need for monitoring HBV vaccine response among HIV-infected children in Morocco, in order to revaccinate non-immunized children.
Language	English
Publishing date	2017-09-29
Publishing country	England
Document type	Journal Article
ISSN	1471-2458
ISSN (online)	1471-2458
DOI	10.1186/s12889-017-4776-8
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Article ; Online: Seroprevalence of measles vaccine antibody response in vertically HIV-infected children, in Morocco.

Haban, Houda / Benchekroun, Soumia / Sadeq, Mina / Tajounte, Latifa / Ahmed, Hinda Jama / Benjouad, Abdelaziz / Amzazi, Said / Oumzil, Hicham / Elharti, Elmir

BMC infectious diseases

2018 Volume 18, Issue 1, Page(s) 680

Abstract: Background: The widespread use of an effective and safe vaccine to measles has substantially decreased morbidity and mortality from this epidemic. Nevertheless, HIV-infected children vaccinated against measles may develop an impaired vaccine response ... ...

Abstract	Background: The widespread use of an effective and safe vaccine to measles has substantially decreased morbidity and mortality from this epidemic. Nevertheless, HIV-infected children vaccinated against measles may develop an impaired vaccine response and remain susceptible to this disease. In Morocco, infants are routinely vaccinated against measles, regardless of their HIV serostatus. An evaluation of the immunization of these children may be of paramount importance to implement timely measures aimed at preventing measles transmission. Methods: In this study, we have enrolled 114 children vaccinated against measles, 50 children prenatally infected with HIV and 64 HIV-uninfected children. For all children, blood samples were taken to measure anti-measles IgG by EIA and CD4 count by flow cytometry. Additionally, HIV viral load was determined by automated real time PCR, for HIV-infected children. Results: The seroprotective rate of IgG anti-measles antibodies was significantly lower among HIV-infected children (26%) compared with HIV-uninfected children (73%) (p < 0.001). Within HIV-infected children group, the comparison of variables between children without seroprotective seroconversion to measles and those with seroprotective immunity, displayed that sex and age were not statistically different, p > 0.999 and p = 0.730, respectively. However, CD4 count was lower among children with negative serostatus to measles (23% versus 32%, p < 0.001). Furthermore, viral load was higher, with 2.91 log Conclusion: The majority of HIV-infected children vaccinated against measles develop a suboptimal seroprotective titer, and therefore remain at risk for this highly infectious disease. These data in combination with international recommendations, including recent WHO guidance on vaccination of HIV-infected children, suggest there is a need for national measures to prevent these children from measles.
MeSH term(s)	Antibodies, Viral/blood ; Antibody Formation ; Case-Control Studies ; Child ; Child, Preschool ; Female ; HIV ; HIV Infections/blood ; HIV Infections/complications ; HIV Infections/epidemiology ; HIV Infections/immunology ; Humans ; Infant ; Infectious Disease Transmission, Vertical/statistics & numerical data ; Male ; Measles/blood ; Measles/complications ; Measles/epidemiology ; Measles Vaccine/immunology ; Measles Vaccine/therapeutic use ; Measles virus/immunology ; Morocco/epidemiology ; Seroepidemiologic Studies ; Vaccination
Chemical Substances	Antibodies, Viral ; Measles Vaccine
Language	English
Publishing date	2018-12-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-018-3590-y
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Article: Characterization of a rare short arm heteromorphism of chromosome 22 in a girl with down-syndrome like facies.

Natiq, Abdelhafid / Elalaoui, Siham Chafai / Liehr, Thomas / Amzazi, Saïd / Sefiani, Abdelaziz

Indian journal of human genetics

2014 Volume 20, Issue 1, Page(s) 89–91

Abstract: Chromosomal heteromorphisms are described as interindividual variation of chromosomes without phenotypic consequence. Chromosomal polymorphisms detected include most regions of heterochromatin of chromosomes 1, 9, 16 and Y and the short arms of all ... ...

Abstract	Chromosomal heteromorphisms are described as interindividual variation of chromosomes without phenotypic consequence. Chromosomal polymorphisms detected include most regions of heterochromatin of chromosomes 1, 9, 16 and Y and the short arms of all acrocentric chromosomes. Here, we report a girl with Down-syndrome such as facies and tremendously enlarged short arm of a chromosome 22. Fluorescence in situ hybridization (FISH) with a probe specific for all acrocentric short arms revealed that the enlargement p arms of the chromosome 22 in question contained exclusively heterochromatic material derived from an acrocentric short arm. Parental studies identified a maternal origin of this heteromorphism. Cryptic trisomy 21 of the Down-syndrome critical region was excluded by a corresponding FISH-probe. Here, we report, to the best of our knowledge, largest ever seen chromosome 22 short arm, being ~×1.5 larger than the normal long arm.
Language	English
Publishing date	2014-05-18
Publishing country	India
Document type	Case Reports
ZDB-ID	2109167-5
ISSN	1998-362X ; 0971-6866
ISSN (online)	1998-362X
ISSN	0971-6866
DOI	10.4103/0971-6866.132767
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Article ; Online: BRCA genetic screening in Middle Eastern and North African: mutational spectrum and founder BRCA1 mutation (c.798_799delTT) in North African.

Laraqui, Abdelilah / Uhrhammer, Nancy / Rhaffouli, Hicham E L / Sekhsokh, Yassine / Lahlou-Amine, Idriss / Bajjou, Tahar / Hilali, Farida / El Baghdadi, Jamila / Al Bouzidi, Abderrahmane / Bakri, Youssef / Amzazi, Said / Bignon, Yves-Jean

Disease markers

2015 Volume 2015, Page(s) 194293

Abstract: Background: The contribution of BRCA1 mutations to both hereditary and sporadic breast and ovarian cancer (HBOC) has not yet been thoroughly investigated in MENA.: Methods: To establish the knowledge about BRCA1 mutations and their correlation with ... ...

Abstract	Background: The contribution of BRCA1 mutations to both hereditary and sporadic breast and ovarian cancer (HBOC) has not yet been thoroughly investigated in MENA. Methods: To establish the knowledge about BRCA1 mutations and their correlation with the clinical aspect in diagnosed cases of HBOC in MENA populations. A systematic review of studies examining BRCA1 in BC women in Cyprus, Jordan, Egypt, Lebanon, Morocco, Algeria, and Tunisia was conducted. Results: Thirteen relevant references were identified, including ten studies which performed DNA sequencing of all BRCA1 exons. For the latter, 31 mutations were detected in 57 of the 547 patients ascertained. Familial history of BC was present in 388 (71%) patients, of whom 50 were mutation carriers. c.798_799delTT was identified in 11 North African families, accounting for 22% of total identified BRCA1 mutations, suggesting a founder allele. A broad spectrum of other mutations including c.68_69delAG, c.181T>G, c.5095C>T, and c.5266dupC, as well as sequence of unclassified variants and polymorphisms, was also detected. Conclusion: The knowledge of genetic structure of BRCA1 in MENA should contribute to the assessment of the necessity of preventive programs for mutation carriers and clinical management. The high prevalence of BC and the presence of frequent mutations of the BRCA1 gene emphasize the need for improving screening programs and individual testing/counseling.
MeSH term(s)	Africa, Northern ; Breast Neoplasms/genetics ; Female ; Gene Frequency ; Genes, BRCA1 ; Genetic Testing ; Heterozygote ; Humans ; Middle East ; Mutation
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	604951-5
ISSN	1875-8630 ; 0278-0240
ISSN (online)	1875-8630
ISSN	0278-0240
DOI	10.1155/2015/194293
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Article ; Online: Contribution of spoligotyping and MIRU-VNTRs to characterize prevalent Mycobacterium tuberculosis genotypes infecting tuberculosis patients in Morocco.

Chaoui, Imane / Zozio, Thierry / Lahlou, Ouafae / Sabouni, Radia / Abid, Mohammed / El Aouad, Rajae / Akrim, Mohammed / Amzazi, Said / Rastogi, Nalin / El Mzibri, Mohammed

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases

2014 Volume 21, Page(s) 463–471

Abstract: In the present study, Mycobacterium tuberculosis complex (MTBC) clinical isolates from culture-positive TB patients in Morocco were studied by spoligotyping and 12-loci MIRU-VNTR typing methods to characterize prevalent genotypes (n = 219 isolates from ... ...

Abstract	In the present study, Mycobacterium tuberculosis complex (MTBC) clinical isolates from culture-positive TB patients in Morocco were studied by spoligotyping and 12-loci MIRU-VNTR typing methods to characterize prevalent genotypes (n = 219 isolates from 208 patients). Spoligotyping resulted in 39 unique patterns and 167 strains in 30 clusters (2-50 strains per cluster). Comparison with international database showed that 29 of 39 unique patterns matched existing shared spoligotype international types (SITs). Nine shared types containing 10 strains were newly created (SIT 2891 to SIT 2899); this led to the description of 69 SITs with 206 strains and two orphan patterns. The most prevalent spoligotype was SIT42 (LAM; n = 50 or 24% of isolates). The repartition of strains according to major MTBC clades was as follows LAM (46.1%)> Haarlem (26%) >ill-defined T superfamily (22.6%) and S clade (0.96%). On the other hand, Beijing, CAS (Central Asian) and EAI (East-African Indian) strains were absent in this setting. Subsequent 12-Loci MIRU typing resulted in a total of 25 SIT/MIT clusters (n = 66 isolates, 2-6 isolates per cluster), with a resulting recent transmission rate of 22.3%. The MIRU-VNTR patterns corresponded to 69 MITs for 138 strains and 46 orphan patterns. The most frequent patterns were MIT43 (n = 8), MIT9 (n = 7) and MIT42 (n = 7). HGDI analysis of the 12 MIRU loci showed that loci 10, 23 and 40 were highly discriminative in our setting. The results also underlined the usefulness of spoligotyping and MIRU-VNTR to detect mixed infections among certain of our TB patients. Globally, the results obtained showed that TB is almost exclusively transmitted in Morocco through evolutionary-modern MTBC lineages belonging to principal genetic groups 2/3 strains (Haarlem, LAM, T), with a high level of biodiversity seen by MIRU typing. This study provides with a 1st global snapshot of MTBC population structure in Morocco, and validates the potential use of spoligotyping in conjunction with minisatellites for future investigations in Morocco that should in future ideally include optimized 15- or 24-loci MIRU-VNTRs.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology ; Bacterial Typing Techniques/methods ; Female ; Genome, Bacterial ; Humans ; Male ; Middle Aged ; Minisatellite Repeats ; Morocco/epidemiology ; Mycobacterium tuberculosis/classification ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Phylogeny ; Phylogeography ; Tuberculosis/epidemiology ; Tuberculosis/microbiology ; Young Adult
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2014-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2037068-4
ISSN	1567-7257 ; 1567-1348
ISSN (online)	1567-7257
ISSN	1567-1348
DOI	10.1016/j.meegid.2013.05.023
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Article ; Online: Mutation screening of the BRCA1 gene in early onset and familial breast/ovarian cancer in Moroccan population.

Laraqui, Abdelilah / Uhrhammer, Nancy / Lahlou-Amine, Idriss / El Rhaffouli, Hicham / El Baghdadi, Jamila / Dehayni, Mohamed / Moussaoui, Rahali Driss / Ichou, Mohamed / Sbitti, Yassir / Al Bouzidi, Abderrahman / Amzazi, Said / Bignon, Yves-Jean

International journal of medical sciences

2012 Volume 10, Issue 1, Page(s) 60–67

Abstract: Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 ... ...

Abstract	Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years)were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T),and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC is also under study.
MeSH term(s)	Adult ; Age of Onset ; BRCA1 Protein/genetics ; Breast Neoplasms/epidemiology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genetics, Population ; Humans ; Middle Aged ; Morocco/epidemiology ; Mutation ; Ovarian Neoplasms/epidemiology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Polymorphism, Genetic
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human
Language	English
Publishing date	2012-12-10
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2151424-0
ISSN	1449-1907 ; 1449-1907
ISSN (online)	1449-1907
ISSN	1449-1907
DOI	10.7150/ijms.5014
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Article ; Online: Computational modeling and druggability assessment of Aggregatibacter actinomycetemcomitans leukotoxin.

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Article ; Online: Assessment of the HBV vaccine response in a group of HIV-infected children in Morocco.

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Article ; Online: Seroprevalence of measles vaccine antibody response in vertically HIV-infected children, in Morocco.

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Article: Characterization of a rare short arm heteromorphism of chromosome 22 in a girl with down-syndrome like facies.

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Article ; Online: BRCA genetic screening in Middle Eastern and North African: mutational spectrum and founder BRCA1 mutation (c.798_799delTT) in North African.

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Article ; Online: Contribution of spoligotyping and MIRU-VNTRs to characterize prevalent Mycobacterium tuberculosis genotypes infecting tuberculosis patients in Morocco.

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Article ; Online: Mutation screening of the BRCA1 gene in early onset and familial breast/ovarian cancer in Moroccan population.

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