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1.
Front Microbiol ; 12: 675528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616371

RESUMO

The rapid spread of SARS-CoV-2 variants has quickly spanned doubts and the fear about their ability escape vaccine protection. Some of these variants initially identified in caged were also found in humans. The claim that these variants exhibited lower susceptibility to antibody neutralization led to the slaughter of 17 million minks in Denmark. SARS-CoV-2 prevalence tests led to the discovery of infected farmed minks worldwide. In this study, we revisit the issue of the circulation of SARS-CoV-2 variants in minks as a model of sarbecovirus interspecies evolution by: (1) comparing human and mink angiotensin I converting enzyme 2 (ACE2) and neuropilin 1 (NRP-1) receptors; (2) comparing SARS-CoV-2 sequences from humans and minks; (3) analyzing the impact of mutations on the 3D structure of the spike protein; and (4) predicting linear epitope targets for immune response. Mink-selected SARS-CoV-2 variants carrying the Y453F/D614G mutations display an increased affinity for human ACE2 and can escape neutralization by one monoclonal antibody. However, they are unlikely to lose most of the major epitopes predicted to be targets for neutralizing antibodies. We discuss the consequences of these results for the rational use of SARS-CoV-2 vaccines.

2.
Front Immunol ; 12: 680146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603278

RESUMO

It has been reported that treatment with ß-lactam antibiotics induces leukopenia and candidemia, worsens the clinical response to anticancer immunotherapy and decreases immune response to vaccination. ß-lactamases can cleave ß-lactam antibiotics by blocking their activity. Two distincts superfamilies of ß-lactamases are described, the serine ß-lactamases and the zinc ion dependent metallo-ß-lactamases. In human, 18 metallo-ß-lactamases encoding genes (hMBLs) have been identified. While the physiological role of most of them remains unknown, it is well established that the SNM1A, B and C proteins are involved in DNA repair. The SNM1C/Artemis protein is precisely associated in the V(D)J segments rearrangement, that leads to immunoglobulin (Ig) and T-cell receptor variable regions, which have a crucial role in the immune response. Thus in humans, SNM1C/Artemis mutation is associated with severe combined immunodeficiency characterized by hypogammaglobulinemia deficient cellular immunity and opportunistic infections. While catalytic site of hMBLs and especially that of the SNM1 family is highly conserved, in vitro studies showed that some ß-lactam antibiotics, and precisely third generation of cephalosporin and ampicillin, inhibit the metallo-ß-lactamase proteins SNM1A & B and the SNM1C/Artemis protein complex. By analogy, the question arises as to whether ß-lactam antibiotics can block the SNM1C/Artemis protein in humans inducing transient immunodeficiency. We reviewed here the literature data supporting this hypothesis based on in silico, in vitro and in vivo evidences. Understanding the impact of ß-lactam antibiotics on the immune cell will offer new therapeutic clues and new clinical approaches in oncology, immunology, and infectious diseases.

3.
Arch Microbiol ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34628511

RESUMO

Strain GD8 is a new species belonging to the order Coriobacteriales that was isolated from fresh stool of a French volunteer. It is an anaerobic Gram-positive bacterium isolated from human gut microbiota. The sequence analysis of the 16S rRNA gene showed that our strain GD8 was 96.2% of similarity with Collinsella massiliensis strain An5 which was the phylogenetically related species. Its genome size is 2,836,446 bp with 64.1 mol% of G + C content. Strain GD8T (= CSUR P2019 = DSM 101062) is the type strain of the new species Collinsella ihumii sp. nov.

4.
Rev Cardiovasc Med ; 22(3): 1063-1072, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565108

RESUMO

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.


Assuntos
Assistência Ambulatorial , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Intervenção Médica Precoce , Hidroxicloroquina/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , COVID-19/diagnóstico , COVID-19/mortalidade , Quimioterapia Combinada , Feminino , França , Hospitalização , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
5.
FEMS Microbiol Lett ; 368(18)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34549292

RESUMO

Strain Marseille-P3519T isolated from the fecal flora of a 25-year-old healthy French woman was a Gram-positive anaerobic bacterium, non-motile and non-spore forming. The 16S rRNA gene sequence of Marseille-P3519 showed 97.73% of sequence similarity with Limosilactobacillus reuteri DSM 20016, the closest species, phylogenetically. Furthermore, the average nucleotide identity of strain Marseille-3519 with its closest related species was 75.8% that was very below the recommended threshold (>95-96%). Its genome had 2 237 367 bp with 45.42 mol% of G + C content. Major fatty acids were C16:0 (50.8%), C18:1n9 (18.0%), C18:2n6 (9.8%) and C19:1n9 (8.9%). It was catalase negative and fermented glycerol, glucose, fructose, D-maltose, lactose and mannose. These findings support that strain Marseille-P3519 ( = CSURP3519 = CECT 30110) is a new member of the genus Limosilactobacillus for which the name Limosilactobacillus caccae sp. nov., is proposed.

6.
ISME J ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556816

RESUMO

The discovery of Acanthamoeba polyphaga Mimivirus, the first isolated giant virus of amoeba, challenged the historical hallmarks defining a virus. Giant virion sizes are known to reach up to 2.3 µm, making them visible by optical microscopy. Their large genome sizes of up to 2.5 Mb can encode proteins involved in the translation apparatus. We have investigated possible energy production in Pandoravirus massiliensis. Mitochondrial membrane markers allowed for the detection of a membrane potential in purified virions and this was enhanced by a regulator of the tricarboxylic acid cycle but abolished by the use of a depolarizing agent. Bioinformatics was employed to identify enzymes involved in virion proton gradient generation and this approach revealed that eight putative P. massiliensis proteins exhibited low sequence identities with known cellular enzymes involved in the universal tricarboxylic acid cycle. Further, all eight viral genes were transcribed during replication. The product of one of these genes, ORF132, was cloned and expressed in Escherichia coli, and shown to function as an isocitrate dehydrogenase, a key enzyme of the tricarboxylic acid cycle. Our findings show for the first time that a membrane potential can exist in Pandoraviruses, and this may be related to tricarboxylic acid cycle. The presence of a proton gradient in P. massiliensis makes this virus a form of life for which it is legitimate to ask the question "what is a virus?".

7.
Front Med (Lausanne) ; 8: 663708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552938

RESUMO

Coronavirus disease 2019 (COVID-19) is now at the forefront of major health challenge faced globally, creating an urgent need for safe and efficient therapeutic strategies. Given the high attrition rates, high costs, and quite slow development of drug discovery, repurposing of known FDA-approved molecules is increasingly becoming an attractive issue in order to quickly find molecules capable of preventing and/or curing COVID-19 patients. Cyclosporin A (CsA), a common anti-rejection drug widely used in transplantation, has recently been shown to exhibit substantial anti-SARS-CoV-2 antiviral activity and anti-COVID-19 effect. Here, we review the molecular mechanisms of action of CsA in order to highlight why this molecule seems to be an interesting candidate for the therapeutic management of COVID-19 patients. We conclude that CsA could have at least three major targets in COVID-19 patients: (i) an anti-inflammatory effect reducing the production of proinflammatory cytokines, (ii) an antiviral effect preventing the formation of the viral RNA synthesis complex, and (iii) an effect on tissue damage and thrombosis by acting against the deleterious action of angiotensin II. Several preliminary CsA clinical trials performed on COVID-19 patients report lower incidence of death and suggest that this strategy should be investigated further in order to assess in which context the benefit/risk ratio of repurposing CsA as first-line therapy in COVID-19 is the most favorable.

9.
Infect Genet Evol ; 95: 105092, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34571275

RESUMO

OBJECTIVES: To compare the demographics, clinical characteristics and severity of patients infected with nine different SARS-CoV-2 variants, during three phases of the COVID-19 epidemic in Marseille. METHODS: A single centre retrospective cohort study was conducted in 1760 patients infected with SARS-CoV-2 of Nextstrain clades 20A, 20B, and 20C (first phase, February-May 2020), Pangolin lineages B.1.177 (we named Marseille-2) and B.1.160 (Marseille-4) variants (second phase, June-December 2020), and B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and A.27 (Marseille-501) variants (third phase, January 2021-today). Outcomes were the occurrence of clinical failures, including hospitalisation, transfer to the intensive-care unit, and death. RESULTS: During each phase, no major differences were observed with regards to age and gender distribution, the prevalence of chronic diseases, and clinical symptoms between variants circulating in a given phase. The B.1.177 and B.1.160 variants were associated with more severe outcomes. Infections occurring during the second phase were associated with a higher rate of death as compared to infections during the first and third phases. Patients in the second phase were more likely to be hospitalised than those in the third phase. Patients infected during the third phase were more frequently obese than others. CONCLUSION: A large cohort study is recommended to evaluate the transmissibility and to better characterise the clinical severity of emerging variants.

10.
Front Med (Lausanne) ; 8: 737602, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540874

RESUMO

Since the start of COVID-19 pandemic the Republic of Djibouti, in the horn of Africa, has experienced two epidemic waves of the virus between April and August 2020 and between February and May 2021. By May 2021, COVID-19 had affected 1.18% of the Djiboutian population and caused 152 deaths. Djibouti hosts several foreign military bases which makes it a potential hot-spot for the introduction of different SARS-CoV-2 strains. We genotyped fifty three viruses that have spread during the two epidemic waves. Next, using spike sequencing of twenty-eight strains and whole genome sequencing of thirteen strains, we found that Nexstrain clades 20A and 20B with a typically European D614G substitution in the spike and a frequent P2633L substitution in nsp16 were the dominant viruses during the first epidemic wave, while the clade 20H South African variants spread during the second wave characterized by an increase in the number of severe forms of COVID-19.

11.
PLoS Negl Trop Dis ; 15(9): e0009767, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34587171

RESUMO

Vector Borne Diseases (VBDs) are considered emerging and re-emerging diseases that represent a global burden. The aim of this study was to explore and characterize vector-borne pathogens in different domestic animal hosts in Egypt. A total of 557 blood samples were collected from different animals using a convenience sampling strategy (203 dogs, 149 camels, 88 cattle, 26 buffaloes, 58 sheep and 33 goats). All samples were tested for multiple pathogens using quantitative PCR and standard PCR coupled with sequencing. We identified Theileria annulata and Babesia bigemina in cattle (15.9 and 1.1%, respectively), T. ovis in sheep and buffaloes (8.6 and 7.7%, respectively) and Ba. canis in dogs (0.5%) as well as Anaplasma marginale in cattle, sheep and camels (20.4, 3.4 and 0.7%, respectively) and Coxiella burnetii in sheep and goats (1.7 and 3%; respectively). New genotypes of An. centrale, An. ovis, An. platys-like and Borrelia theileri were found in cattle (1.1,3.4, 3.4 and 3.4%, respectively), An. platys-like in buffaloes (7.7%), An. marginale, An. ovis, An. platys-like and Bo. theileri in sheep (3.4, 1.7, 1.7 and 3.4%, respectively), An. platys, An. platys-like and Setaria digitata in camels (0.7, 5.4 and 0.7%, respectively) and Rickettsia africae-like, An. platys, Dirofilaria repens and Acanthocheilonema reconditum in dogs (1.5, 3.4, 1 and 0.5%, respectively). Co-infections were found in cattle, sheep and dogs (5.7, 1.7, 0.5%, respectively). For the first time, we have demonstrated the presence of several vector-borne zoonoses in the blood of domestic animals in Egypt. Dogs and ruminants seem to play a significant role in the epidemiological cycle of VBDs.

14.
Vector Borne Zoonotic Dis ; 21(9): 659-666, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34534024

RESUMO

Q fever and tick-borne borreliosis are two zoonotic diseases rarely diagnosed in Senegalese health facilities, particularly in rural areas. Our study aims to better understand the circulation of Coxiella burnetii and Borrelia spp. DNA on human skin and the domestic environment in rural areas. Cutaneous swabs were taken from febrile patients being treated for borreliosis and/or Q fever, the members of patients' households and control households in the Niakhar area. Dust samples were also collected from 90 households where 54 cases of borreliosis and Q fever were reported as well as from the households of members of control populations in Dielmo, Ndiop, and Niakhar. C. burnetii and Borrelia spp. DNA were detected by quantitative PCR in cutaneous swabs and dust samples targeting spacers IS1111_IS30A and Bor 16S gene. Of 1365 persons tested, 76 were shown to carry C. burnetii, 13 Borrelia spp., and 6 were identified as carrying both C. burnetii and Borrelia spp. The prevalence of Borrelia spp. DNA in households was 16.7% in Dielmo, 6.7% in Ndiop, and 23.3% in all other villages in the Niakhar area, and the presence of C. burnetii in the same localities was 10%, 13.3% and 66.7%, respectively. Furthermore, C. burnetii genotyping identified the presence of Multispacer Sequence Typing group 6. These results revealed for the first time the carriage on the skin of C. burnetii and Borrelia spp. DNA in humans and its wide distribution across households. Our findings suggest that many populations are exposed to these diseases, with frequent contaminating cases of infectious origin arising from the domestic environment.

15.
One Health ; 13: 100293, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34377760

RESUMO

Dogs are occasionally susceptible to SARS-CoV-2, developing few or no clinical signs. Epidemiological surveillance of SARS-CoV-2 in dogs requires testing to distinguish it from other canine coronaviruses. In the last year, significant advances have been made in the diagnosis of SARS-CoV-2, allowing its surveillance in both human and animal populations. Here, using ELISA and automated western blotting (AWB) assays, we performed a longitudinal study on 809 apparently healthy dogs from different regions of France to investigate anti-SARS-CoV-2 antibodies. There were three main groups: (i) 356 dogs sampled once before the pandemic, (ii) 235 dogs sampled once during the pandemic, and (iii) 218 dogs, including 82 dogs sampled twice (before and during the pandemic), 125 dogs sampled twice during the pandemic and 11 dogs sampled three times (once before and twice during the pandemic). Using ELISA, seroprevalence was significantly higher during the pandemic [5.5% (25/453)] than during the pre-pandemic period [1.1% (5/449)]. Among the 218 dogs sampled twice, at least 8 ELISA-seroconversions were observed. ELISA positive pre-pandemic sera were not confirmed in serial tests by AWB, indicating possible ELISA cross-reactivity, probably with other canine coronaviruses. A significant difference was observed between these two serological tests (Q = 88, p = 0.008). A clear correlation was observed between SARS-CoV-2 seroprevalence in dogs and the incidence of SARS-CoV-2 infection in human population from the same area. AWB could be used as a second line assay to confirm the doubtful and discrepant ELISA results in dogs. Our results confirm the previous experimental models regarding the susceptibility of dogs to SARS-CoV-2, suggesting that viral transmission from and between dogs is weak or absent. However, the new variants with multiple mutations could adapt to dogs; this hypothesis cannot be ruled out in the absence of genomic data on SARS-CoV-2 from dogs.

16.
J Clin Med ; 10(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34361994

RESUMO

The objective of this paper is to describe the surveillance system MIDaS and to show how this system has been used for evaluating the consequences of the French COVID-19 lockdown on the bacterial mix of AP-HM and the antibiotic resistance. MIDas is a kind of surveillance activity hub, allowing the automatic construction of surveillance control boards. We investigated the diversity and resistance of bacterial agents from respiratory, blood, and urine samples during the lockdown period (from week 12 to 35 of 2020), using the same period of years from 2017 to 2019 as control. Taking into account the drop in patient recruitment, several species have exhibited significant changes in their relative abundance (either increasing or decreasing) with changes up to 9%. The changes were more important for respiratory and urine samples than for blood samples. The relative abundance in respiratory samples for the whole studied period was higher during the lockdown. A significant increase in the percentage of wild phenotypes during the lockdown was observed for several species. The use of the MIDaS syndromic collection and surveillance system made it possible to efficiently detect, analyze, and follow changes of the microbiological population as during the lockdown period.

17.
J Clin Med ; 10(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34362060

RESUMO

Since summer 2020, SARS-CoV-2 strains at the origin of the COVID-19 pandemic have suddenly been replaced by new SARS-CoV-2 variants, some of which are highly transmissible and spread at a high rate. These variants include the Marseille-4 lineage (Nextclade 20A.EU2) in Europe, the 20I/501Y.V1 variant first detected in the UK, the 20H/501Y.V2 variant first detected in South Africa, and the 20J/501Y.V3 variant first detected in Brazil. These variants are characterized by multiple mutations in the viral spike protein that is targeted by neutralizing antibodies elicited in response to infection or vaccine immunization. The usual coronavirus mutation rate through genetic drift alone cannot account for such rapid changes. Recent reports of the occurrence of such mutations in immunocompromised patients who received remdesivir and/or convalescent plasma or monoclonal antibodies to treat prolonged SARS-CoV-2 infections led us to hypothesize that experimental therapies that fail to cure the patients from COVID-19 could favor the emergence of immune escape SARS-CoV-2 variants. We review here the data that support this hypothesis and urge physicians and clinical trial promoters to systematically monitor viral mutations by whole-genome sequencing for patients who are administered these treatments.

18.
Front Immunol ; 12: 698121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367158

RESUMO

Epidemiological studies and clinical observations show evidence of sexual dimorphism in infectious diseases. Women are at less risk than men when it comes to developing most infectious diseases. However, understanding these observations requires a gender approach that takes into account an analysis of both biological and social factors. The host's response to infection differs in males and females because sex differences have an impact on hormonal and chromosomal control of immunity. Estradiol appears to confer protective immunity, while progesterone and testosterone suppress anti-infectious responses. In addition, genetic factors, including those associated with sex chromosomes, also affect susceptibility to infections. Finally, differences in occupational activities, lifestyle, and comorbidities play major roles in exposure to pathogens and management of diseases. Hence, considering sexual dimorphism as a critical variable for infectious diseases should be one of the steps taken toward developing personalized therapeutic approaches.

19.
Arch Microbiol ; 203(9): 5817-5823, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34420080

RESUMO

Thanks to its ability to isolate previously uncultured bacterial species, culturomics has dynamized the study of the human microbiota. A new bacterial species, Gemella massiliensis Marseille-P3249T, was isolated from a sputum sample of a healthy French man. Strain Marseille-P3249T is a facultative anaerobe, catalase-negative, Gram positive, coccus, and unable to sporulate. The major fatty acids were C16:0 (34%), C18:1n9 (28%), C18:0 (15%) and C18:2n6 (13%). Its 16S rRNA sequence exhibits a 98.3% sequence similarity with Gemella bergeri strain 617-93T, its phylogenetically closest species with standing in nomenclature. Its digital DNA-DNA hybridization (dDDH) and OrthoANI values with G. bergeri of only 59.7 ± 5.6% and 94.8%, respectively. These values are lower than the thresholds for species delineation (> 70% and > 95%, respectively). This strain grows optimally at 37 °C and its genome is 1.80 Mbp long with a 30.5 mol% G + C content. Based on these results, we propose the creation of the new species Gemella massilienis sp. nov., strain Marseille-P3249T (= CSUR P3249 = DSMZ 103940).


Assuntos
Gemella , Filogenia , Escarro/microbiologia , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Gemella/classificação , Gemella/isolamento & purificação , Humanos , Masculino , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética
20.
Pathogens ; 10(8)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34451527

RESUMO

Dysbiosis, developed upon antibiotic administration, results in loss of diversity and shifts in the abundance of gut microbes. Doxycycline is a tetracycline antibiotic widely used for malaria prophylaxis in travelers. We prospectively studied changes in the fecal microbiota of 15 French soldiers after a 4-month mission to Mali with doxycycline malaria prophylaxis, compared to changes in the microbiota of 28 soldiers deployed to Iraq and Lebanon without doxycycline. Stool samples were collected with clinical data before and after missions, and 16S rRNA sequenced on MiSeq targeting the V3-V4 region. Doxycycline exposure resulted in increased alpha-biodiversity and no significant beta-dissimilarities. It led to expansion in Bacteroides, with a reduction in Bifidobacterium and Lactobacillus, as in the group deployed without doxycycline. Doxycycline did not alter the community structure and was specifically associated with a reduction in Escherichia and expression of Rothia. Differences in the microbiota existed at baseline between military units but not within the studied groups. This group-effect highlighted the risk of a Simpson paradox in microbiome studies.

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