Post-Translational Variants of Major Proteins in Amyotrophic Lateral Sclerosis Provide New Insights into the Pathophysiology of the Disease.

Post-translational modifications (PTMs) affecting proteins during or after their synthesis play a crucial role in their localization and function. The modification of these PTMs under pathophysiological conditions, i.e., their appearance, disappearance, or variation in quantity caused by a pathological environment or a mutation, corresponds to post-translational variants (PTVs). These PTVs can be directly or indirectly involved in the pathophysiology of diseases. Here, we present the PTMs and PTVs of four major amyotrophic lateral sclerosis (ALS) proteins, SOD1, TDP-43, FUS, and TBK1. These modifications involve acetylation, phosphorylation, methylation, ubiquitination, SUMOylation, and enzymatic cleavage. We list the PTM positions known to be mutated in ALS patients and discuss the roles of PTVs in the pathophysiological processes of ALS. In-depth knowledge of the PTMs and PTVs of ALS proteins is needed to better understand their role in the disease. We believe it is also crucial for developing new therapies that may be more effective in ALS.

Genomic analysis of Paenibacillus sp. MDMC362 from the Merzouga desert leads to the identification of a potentially thermostable catalase.

Microorganisms in hot deserts face heat and other environmental conditions, such as desiccation, UV radiation, or low nutrient availability. Therefore, this hostile environment harbour microorganisms with acquired characteristics related to survival in their habitat, which can be exploited in biotechnology. In this work, the genome of Paenibacillus sp. MDMC362 isolated from the Merzouga desert in Morocco was sequenced to understand its survival strategy's genetic basis; and to evaluate the thermostability of a catalase extracted from genomic annotation files using molecular dynamics. Paenibacillus sp. MDMC362 genome was rich in genetic elements involved in the fight against different stresses, notably temperature stress, UV radiations, osmotic stress, carbon starvation, and oxidative stress. Indeed, we could identify genes of the operons groES-groEL and hrcA-grpE-dnaK and those involved in the different stages of sporulation, which can help the bacteria to survive the high temperatures imposed by a desertic environment. We also observed the genetic components of the UvrABC system and additional mechanisms involved in DNA repair, which help overcome UV radiation damage. Other genes have been identified in the genome, like those coding for ectoine and proline, that aids fight osmotic stress and desiccation. Catalase thermostability investigation using molecular dynamics showed that the protein reached stability and conserved its compactness at temperatures up to 373.15 K. These results suggest a potential thermostability of the enzyme. Since the studied protein is a core protein, thermostability could be conserved among Paenibacillus sp. MDMC362 closely related strains; however, bacteria from harsh environments may have a slight advantage regarding protein stability.

Genomic analysis of two Bacillus safensis isolated from Merzouga desert reveals desert adaptive and potential plant growth-promoting traits.

Deserts represent extreme environments for microorganisms, and conditions such as high soil salinity, nutrient deficiency, and increased levels of UV radiation make desert soil communities of high biotechnological potential. In this study, we isolated, sequenced, and assembled the genomes of Bacillus safensis strains BcP62 and Bcs93, to which we performed comparative genome analyses. Using the DDH and ANI of both strains with the available B. safensis genomes, we identified three potential subspecies within this group. Intra-species core genome phylogenetic analysis did not result in clustering genomes by niche type, with some exceptions. This study also revealed that the genomes of the analyzed strains possessed plant growth-promoting characteristics, most of which were conserved in all B. safensis strains. Furthermore, we highlight the genetic features of B. safensis BcP62 and Bcs93 related to survival in the Merzouga desert in Morocco. These strains could be potentially used in agriculture as PGPB in extreme environments, given their high tolerability to unfavorable conditions.

Fusarium graminearum Infection Strategy in Wheat Involves a Highly Conserved Genetic Program That Controls the Expression of a Core Effectome.

Fusarium graminearum, the main causal agent of Fusarium Head Blight (FHB), is one of the most damaging pathogens in wheat. Because of the complex organization of wheat resistance to FHB, this pathosystem represents a relevant model to elucidate the molecular mechanisms underlying plant susceptibility and to identify their main drivers, the pathogen's effectors. Although the F. graminearum catalog of effectors has been well characterized at the genome scale, in planta studies are needed to confirm their effective accumulation in host tissues and to identify their role during the infection process. Taking advantage of the genetic variability from both species, a RNAseq-based profiling of gene expression was performed during an infection time course using an aggressive F. graminearum strain facing five wheat cultivars of contrasting susceptibility as well as using three strains of contrasting aggressiveness infecting a single susceptible host. Genes coding for secreted proteins and exhibiting significant expression changes along infection progress were selected to identify the effector gene candidates. During its interaction with the five wheat cultivars, 476 effector genes were expressed by the aggressive strain, among which 91% were found in all the infected hosts. Considering three different strains infecting a single susceptible host, 761 effector genes were identified, among which 90% were systematically expressed in the three strains. We revealed a robust F. graminearum core effectome of 357 genes expressed in all the hosts and by all the strains that exhibited conserved expression patterns over time. Several wheat compartments were predicted to be targeted by these putative effectors including apoplast, nucleus, chloroplast and mitochondria. Taken together, our results shed light on a highly conserved parasite strategy. They led to the identification of reliable key fungal genes putatively involved in wheat susceptibility to F. graminearum, and provided valuable information about their putative targets.

Comparative Genomics of Eight Fusarium graminearum Strains with Contrasting Aggressiveness Reveals an Expanded Open Pangenome and Extended Effector Content Signatures.

Fusarium graminearum, the primary cause of Fusarium head blight (FHB) in small-grain cereals, demonstrates remarkably variable levels of aggressiveness in its host, producing different infection dynamics and contrasted symptom severity. While the secreted proteins, including effectors, are thought to be one of the essential components of aggressiveness, our knowledge of the intra-species genomic diversity of F. graminearum is still limited. In this work, we sequenced eight European F. graminearum strains of contrasting aggressiveness to characterize their respective genome structure, their gene content and to delineate their specificities. By combining the available sequences of 12 other F. graminearum strains, we outlined a reference pangenome that expands the repertoire of the known genes in the reference PH-1 genome by 32%, including nearly 21,000 non-redundant sequences and gathering a common base of 9250 conserved core-genes. More than 1000 genes with high non-synonymous mutation rates may be under diverse selection, especially regarding the trichothecene biosynthesis gene cluster. About 900 secreted protein clusters (SPCs) have been described. Mostly localized in the fast sub-genome of F. graminearum supposed to evolve rapidly to promote adaptation and rapid responses to the host's infection, these SPCs gather a range of putative proteinaceous effectors systematically found in the core secretome, with the chloroplast and the plant nucleus as the main predicted targets in the host cell. This work describes new knowledge on the intra-species diversity in F. graminearum and emphasizes putative determinants of aggressiveness, providing a wealth of new candidate genes potentially involved in the Fusarium head blight disease.

A Comprehensive Analysis of 3 Moroccan Genomes Revealed Contributions From Both African and European Ancestries.

Genetic variations in the human genome represent the differences in DNA sequence within individuals. This highlights the important role of whole human genome sequencing which has become the keystone for precision medicine and disease prediction. Morocco is an important hub for studying human population migration and mixing history. This study presents the analysis of 3 Moroccan genomes; the variant analysis revealed 6 379 606 single nucleotide variants (SNVs) and 1 050 577 small InDels. Of those identified SNVs, 219 152 were novel, with 1233 occurring in coding regions, and 5580 non-synonymous single nucleotide variants (nsSNP) variants were predicted to affect protein functions. The InDels produced 1055 coding variants and 454 non-3n length variants, and their size ranged from -49 and 49 bp. We further analysed the gene pathways of 8 novel coding variants found in the 3 genomes and revealed 5 genes involved in various diseases and biological pathways. We found that the Moroccan genomes share 92.78% of African ancestry, and 92.86% of Non-Finnish European ancestry, according to the gnomAD database. Then, population structure inference, by admixture analysis and network-based approach, revealed that the studied genomes form a mixed population structure, highlighting the increased genetic diversity in Morocco.

Draft Genome Sequences of Three Pseudomonas chengduensis Strains Isolated from Desert Soil in Morocco.

We report the draft genome sequences of three Pseudomonas chengduensis strains isolated from the sand dunes of the Merzouga (MDMC17 strain) and Erg Lihoudi (MDMC216 and MDMC224 strains) regions in the Moroccan desert. These bacteria are able to tolerate the harsh environmental conditions of the desert ecosystem.

Draft Genome Sequences of Two Enterobacter hormaechei subsp. xiangfangensis Strains Isolated from the Moroccan Sahara.

We report the draft genome sequences of Enterobacter hormaechei subsp. xiangfangensis strains MDMC82 and MDMC76, which were isolated from the sand dunes of the Merzouga desert in the Moroccan Sahara. These bacteria are able to tolerate the harsh environmental conditions of the Moroccan desert.

IDbSV: An Open-Access Repository for Monitoring SARS-CoV-2 Variations and Evolution.

Ending COVID-19 pandemic requires a collaborative understanding of SARS-CoV-2 and COVID-19 mechanisms. Yet, the evolving nature of coronaviruses results in a continuous emergence of new variants of the virus. Central to this is the need for a continuous monitoring system able to detect potentially harmful variants of the virus in real-time. In this manuscript, we present the International Database of SARS-CoV-2 Variations (IDbSV), the result of ongoing efforts in curating, analyzing, and sharing comprehensive interpretation of SARS-CoV-2's genetic variations and variants. Through user-friendly interactive data visualizations, we aim to provide a novel surveillance tool to the scientific and public health communities. The database is regularly updated with new records through a 4-step workflow (1-Quality control of curated sequences, 2-Call of variations, 3-Functional annotation, and 4-Metadata association). To the best of our knowledge, IDbSV provides access to the largest repository of SARS-CoV-2 variations and the largest analysis of SARS-CoV-2 genomes with over 60 thousand annotated variations curated from the 1,808,613 genomes alongside their functional annotations, first known appearance, and associated genetic lineages, enabling a robust interpretation tool for SARS-CoV-2 variations to help understanding SARS-CoV-2 dynamics across the world.

Searching for FHB Resistances in Bread Wheat: Susceptibility at the Crossroad.

Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is one of the most devastating fungal wheat diseases. During the past decades, many efforts have been deployed to dissect FHB resistance, investigating both the wheat responses to infection and, more recently, the fungal determinants of pathogenicity. Although no total resistance has been identified so far, they demonstrated that some plant functions and the expression of specific genes are needed to promote FHB. Associated with the increasing list of F. graminearum effectors able to divert plant molecular processes, this fact strongly argues for a functional link between susceptibility-related factors and the fate of this disease in wheat. In this review, we gather more recent data concerning the involvement of plant and fungal genes and the functions and mechanisms in the development of FHB susceptibility, and we discuss the possibility to use them to diversify the current sources of FHB resistance.

Draft Genome Sequence of Stenotrophomonas maltophilia MDMC339, Isolated from Soil of Merzouga Desert in Morocco.

Here, we report the draft genome sequence of Stenotrophomonas maltophilia MDMC339, a strain able to survive in the difficult conditions imposed by the Merzouga desert. The analyzed genome contains 4,788,525 bp with 4,262 genes coding for proteins, including several genes related to stress.

Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geo-distribution and a rich genetic variations of hotspots mutations.

In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variants sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 68 recurrent mutations, including ten hotspot non-synonymous mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed that certain genotypes are specific to geographic locations. We also identified co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. The phylogentic analysis identified two major Clades C1 and C2 harboring mutations L3606F and G614D, respectively and both emerging for the first time in China. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets. We have also created an inclusive unified database (http://covid-19.medbiotech.ma) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.

Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the "Confined Virus"?

The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database. Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely.

Genome Sequences of Six SARS-CoV-2 Strains Isolated in Morocco, Obtained Using Oxford Nanopore MinION Technology.

Here, we report the draft genome sequences of six severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. SARS-CoV-2 is responsible for the COVID-19 pandemic, which started at the end of 2019 in Wuhan, China. The isolates were obtained from nasopharyngeal swabs from Moroccan patients with COVID-19. Mutation analysis revealed the presence of the spike D614G mutation in all six genomes, which is widely present in several genomes around the world.

Genome Sequence of Fusarium graminearum Strain MDC_Fg1, Isolated from Bread Wheat Grown in France.

Fusarium graminearum is a major fungal pathogen that induces Fusarium head blight (FHB), a devastating disease of small-grain cereals worldwide. This announcement provides the whole-genome sequence of a highly virulent and toxin-producing French isolate, MDC_Fg1.

First Whole-Genome Sequences of Two Multidrug-Resistant Acinetobacter baumannii Strains Isolated from a Moroccan Hospital Floor.

This report describes the whole-genome shotgun sequences of two multidrug-resistant Acinetobacter baumannii strains, ABE8_07 and ABE12_M, isolated from a Moroccan hospital floor. These two genome sequences will initiate the study and characterization of the Acinetobacter baumannii genome in Morocco.

Clonal diversity and detection of carbapenem resistance encoding genes among multidrug-resistant Acinetobacter baumannii isolates recovered from patients and environment in two intensive care units in a Moroccan hospital.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii has recently been defined by the World Health Organization as a critical pathogen. The aim of this study was to compare clonal diversity and carbapenemase-encoding genes of A. baumannii isolates collected from colonized or infected patients and hospital environment in two intensive care units (ICUs) in Morocco. METHODS: The patient and environmental sampling was carried out in the medical and surgical ICUs of Mohammed V Military teaching hospital from March to August 2015. All A. baumannii isolates recovered from clinical and environmental samples, were identified using routine microbiological techniques and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Antimicrobial susceptibility testing was performed using disc diffusion method. The carbapenemase-encoding genes were screened for by PCR. Clonal relatedness was analyzed by digestion of the DNA with low frequency restriction enzymes and pulsed field gel electrophoresis (PFGE) and the multi locus sequence typing (MLST) was performed on two selected isolates from two major pulsotypes. RESULTS: A total of 83 multidrug-resistant A. baumannii isolates were collected: 47 clinical isolates and 36 environmental isolates. All isolates were positive for the blaOXA51-like and blaOXA23-like genes. The coexistence of blaNDM-1/blaOXA-23-like and blaOXA 24-like/blaOXA-23-like were detected in 27 (32.5%) and 2 (2.4%) of A. baumannii isolates, respectively. The environmental samples and the fecally-colonized patients were significantly identified (p < 0.05) as the most common sites of isolation of NDM-1-harboring isolates. PFGE grouped all isolates into 9 distinct clusters with two major groups (0007 and 0008) containing up to 59% of the isolates. The pulsotype 0008 corresponds to sequence type (ST) 195 while pulsotype 0007 corresponds to ST 1089.The genetic similarity between the clinical and environmental isolates was observed in 80/83 = 96.4% of all isolates, belonging to 7 pulsotypes. CONCLUSION: This study shows that the clonal spread of environmental A. baumannii isolates is related to that of clinical isolates recovered from colonized or infected patients, being both associated with a high prevalence of the blaOXA23-like and blaNDM-1 genes. These findings emphasize the need for prioritizing the bio-cleaning of the hospital environment to control and prevent the dissemination of A. baumannii clonal lineages.

Whole-Genome Shotgun Sequences of Three Multidrug-Resistant Mycobacterium tuberculosis Strains Isolated from Morocco.

Tuberculosis is a contagious disease that usually attacks the lungs but sometimes attacks other parts of the body, such as the kidneys, glands, and bones. It is an endemic and major public health problem in Morocco. Tuberculosis is transmitted through the airways via the inhalation of microdroplets containing Mycobacterium tuberculosis We present here the whole-genome shotgun sequences of three multidrug-resistant M. tuberculosis strains isolated from Morocco.