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1.
Artigo em Inglês | MEDLINE | ID: mdl-33397708

RESUMO

Listeria monocytogenes (Lm) is a major human and animal foodborne pathogen. However, data from environmental reservoirs remain scarce. Here, we used whole genome sequencing to characterize Listeria spp. isolates recovered over one year from wild animals in their natural habitats in Spain. Three different Listeria spp. [Lm (n=19), Listeria ivanovii subsp. londoniensis (Liv, n=4) and Listeria innocua (Lin, n=3)] were detected in 23 animal tonsils (9 deer, 14 wild boars) and 2 feeding throughs. No Listeria spp. was detected in feces. Lm was detected in tonsils of 44.4% (8 out of 18) deer and 40.7% (11 out of 27) wild boars. Lm isolates belonged to 3 different cgMLST types (CTs) of 3 distinct sublineages (SL1, SL387 and SL155) from lineages I and II. While cgMLST type L1-SL1-ST1-CT5279 (IVb, CC1) occurred only in one animal, types L1-SL387-ST388-CT5239 (IVb, CC388) and L2-SL155-ST155-CT1170 (IIa, CC155) were retrieved from multiple animals. In addition, L1-SL387-ST388-CT5239 (IVb, CC388) isolates were collected 1 year apart, revealing its long-term occurrence within the animal population and/or environmental reservoir. The presence of identical Lm strains in deer and wild boars suggest contamination from a common food or environmental source, although interhost transmission cannot be excluded. Pathogenicity islands were present in 100% (LIPI-1), 5% (LIPI-3) and 79% (LIPI-4) of the Lm isolates and all Lm lineage II isolates (n=3) carried SSI-1 stress islands. This study highlights the need for monitoring Lm environmental contamination and the importance of tonsils as a possible Lm intra-host reservoir.Importance: Listeria monocytogenes (Lm) is a foodborne bacterial pathogen responsible for listeriosis. Whole genome sequencing has been extensively used in public health and food industries to characterize circulating Listeria isolates, but genomic data on isolates occurring in natural environments and wild animals is still scarce. Here, we show that wild animals carry pathogenic Listeria and that the same genotypes can be found at different time points in different host species. This work highlights the need of Listeria spp. monitoring of environmental contamination and the importance of tonsils as a possible Lm intra-host reservoir.

3.
Curr Biol ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33333010

RESUMO

Listeria monocytogenes is a foodborne bacterial pathogen that causes human listeriosis, a severe systemic infection.1 Its translocation across the intestinal epithelium is mediated by the interaction of internalin (InlA), a Listeria surface protein, with its host-species-specific receptor E-cadherin (Ecad).2-5 It occurs through goblet cells, on which Ecad is luminally accessible,6 via an unknown mechanism. In the absence of cell lines recapitulating this phenotype in vitro, we developed an ex vivo experimental system, based on the intraluminal microinjection of Listeria in untreated, pharmacologically treated, and genetically modified intestinal organoids. Using both live light-sheet microscopy and confocal imaging, we show that Listeria translocates through goblet cells within a membrane vacuole in an InlA- and microtubule-dependent manner. As Ecad undergoes constant apical-basal recycling,7,8 we hypothesized that Lm may transit through goblet cells by hijacking Ecad recycling pathway. Indeed, Listeria is stuck at goblet cell apex when Ecad endocytosis is blocked and remains trapped intracellularly at the basolateral pole of goblet cells when Rab11-dependent Ecad recycling is compromised. Together, these results show that Listeria, upon docking onto its luminally accessible receptor Ecad, hijacks its recycling pathway to be transferred by transcytosis across goblet cells. Live imaging of host-pathogen interactions in organoids is a promising approach to dissect their underlying cell and molecular biology.

4.
Curr Opin Microbiol ; 59: 95-101, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33307408

RESUMO

Listeria monocytogenes (Lm) is a foodborne bacterial pathogen that causes listeriosis, a severe infection that manifests as bacteremia and meningo-encephalitis mostly in immunocompromised individuals, and maternal-fetal infection. A critical pathogenic determinant of Lm relies on its ability to actively cross the intestinal barrier, disseminate systemically and cross the blood-brain and placental barriers. Here we illustrate how Lm both evades innate immunity, favoring its dissemination in host tissues, and triggers innate immune defenses that participate to its control.

5.
Int J Syst Evol Microbiol ; 70(11): 5868-5879, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33016862

RESUMO

In the context of a study on the occurrence of Listeria species in an animal farm environment in Valencia, Spain, six Listeria-like isolates could not be assigned to any known species. Phylogenetic analysis based on the 16S rRNA gene and on 231 Listeria core genes grouped these isolates in a monophyletic clade within the genus Listeria, with highest similarity to Listeria thailandensis. Whole-genome sequence analyses based on in silico DNA-DNA hybridization, the average nucleotide blast and the pairwise amino acid identities against all currently known Listeria species confirmed that these isolates constituted a new taxon within the genus Listeria. Phenotypically, these isolates differed from other Listeria species mainly by the production of acid from inositol, the absence of acidification in presence of methyl α-d-glucoside, and the absence of α-mannosidase and nitrate reductase activities. The name Listeria valentina sp. nov. is proposed for this novel species, and the type strain is CLIP 2019/00642T (=CIP 111799T=DSM 110544T).


Assuntos
Água Potável/microbiologia , Fezes/microbiologia , Listeria/classificação , Filogenia , Ovinos/microbiologia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Fazendas , Ácidos Graxos/química , Listeria/isolamento & purificação , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Espanha , Microbiologia da Água
6.
Clin Infect Dis ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32614433

RESUMO

Prolonged measles virus detection in maternal saliva and blood was evidenced in 6 pregnant women. Maternal-fetal transmission was evidenced in 2/4 infants who were asymptomatic at birth, 21-24 weeks after maternal infection. Whereas peripartum congenital measles is severe, asymptomatic measles virus vertical transmission can occur earlier in pregnancy.

7.
Virulence ; 11(1): 398-399, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32363994
8.
Virulence ; 11(1): 391-397, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32363991

RESUMO

Listeriosis is a rare and severe foodborne infection caused by Listeria monocytogenes. It manifests as septicemia, neurolisteriosis, and maternal-fetal infection. In pregnancy, it may cause maternal fever, premature delivery, fetal loss, neonatal systemic and central nervous system infections. Maternal listeriosis is mostly reported during the 2nd and 3rd trimester of pregnancy, as sporadic cases or in the context of outbreaks. Strains belonging to clonal complexes 1, 4 and 6, referred to as hypervirulent, are the most associated to maternal-neonatal infections. Here we review the clinical, pathophysiological, and microbiological features of maternal-neonatal listeriosis.

9.
Cell Microbiol ; 22(4): e13186, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32185900

RESUMO

Listeria monocytogenes causes listeriosis, a systemic infection which manifests as bacteremia, often complicated by meningoencephalitis in immunocompromised individuals and the elderly, and fetal-placental infection in pregnant women. It has emerged over the past decades as a major foodborne pathogen, responsible for numerous outbreaks in Western countries, and more recently in Africa. L. monocytogenes' pathogenic properties have been studied in detail, thanks to concomitant advances in biological sciences, in particular molecular biology, cell biology and immunology. L. monocytogenes has also been instrumental to basic advances in life sciences. L. monocytogenes therefore stands both a tool to understand biology and a model in infection biology. This review briefly summarises the clinical and some of the pathophysiological features of listeriosis. In the context of this special issue, it highlights some of the major discoveries made by Pascale Cossart in the fields of molecular and cellular microbiology since the mid-eighties regarding the identification and characterisation of multiple bacterial and host factors critical to L. monocytogenes pathogenicity. It also briefly summarises some of the key findings from our laboratory on this topic over the past years.

10.
N Engl J Med ; 382(7): 632-643, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053299

RESUMO

BACKGROUND: An outbreak of listeriosis was identified in South Africa in 2017. The source was unknown. METHODS: We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018. RESULTS: A total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case-control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of L. monocytogenes ST6 infections. CONCLUSIONS: This investigation showed that in a middle-income country with a high prevalence of HIV infection, L. monocytogenes caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.


Assuntos
Surtos de Doenças , Doenças Transmitidas por Alimentos/epidemiologia , Listeria monocytogenes/isolamento & purificação , Listeriose/epidemiologia , Produtos da Carne/microbiologia , Adolescente , Adulto , Idoso , Técnicas de Tipagem Bacteriana , Estudos de Casos e Controles , Feminino , Doenças Transmitidas por Alimentos/etiologia , Doenças Transmitidas por Alimentos/mortalidade , Infecções por HIV/complicações , HIV-1 , Humanos , Recém-Nascido , Listeria monocytogenes/genética , Listeriose/etiologia , Listeriose/mortalidade , Masculino , Produtos da Carne/efeitos adversos , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Recall e Retirada de Produto , Distribuição por Sexo , África do Sul/epidemiologia , Sequenciamento Completo do Genoma , Adulto Jovem
11.
Clin Infect Dis ; 71(7): e186-e190, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31916572

RESUMO

We provide the first description of a series of 9 severe gynecological infections (mastitis and pelvic cellulitis) occurring in the French national cohort of women with STAT3 deficiency. Each episode had unique features in terms of clinical presentation, microbial documentation, location, treatment duration, and related persistent esthetic damage.

12.
Eur J Clin Microbiol Infect Dis ; 39(5): 999-1002, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31955353

RESUMO

The etiologies of undifferentiated fever in pregnant women have not been studied thoroughly. Because of its non-specific presentation but severe prognosis, listeriosis is often suspected in this setting, but in most cases not confirmed. We studied the causes of undifferentiated fever in pregnant women who received preemptive listeriosis treatment. We conducted from November 1, 2011, to June 30, 2013, a prospective multicentric observational cohort study of pregnant women referred to obstetrical wards with undifferentiated fever and who received listeriosis preemptive treatment. Clinical and biological features, treatment, outcome, and final diagnosis were collected. We enrolled 103 febrile pregnant women. A cause was identified in 77/103 (75%): viral infection in 52/103 (50%, influenza in 21 (20%)), bacterial infection in 22 (21%, including 16 pyelonephritis (16%) and 3 pneumonias (3%)), and TORCH infection in 3 (3%, varicella, toxoplasmosis, and cytomegalovirus primo-infections, n=1, each). Viral infections collected during influenza outbreaks (December-March) accounted for 43/57 (75%) cases. Two fetal losses were reported in the context of febrile pneumonia. Final diagnoses required adapting medical care in 46/77 (60%) of cases, for bacterial, influenza, or TORCH infections. A large array of benign to potentially severe infections manifests as acute undifferentiated fever in pregnant women, requiring careful repeated evaluation.


Assuntos
Febre/classificação , Febre/etiologia , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Surtos de Doenças , Feminino , França , Humanos , Listeriose/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/virologia , Gestantes , Estudos Prospectivos , Viroses/complicações , Viroses/diagnóstico
14.
Cell Host Microbe ; 26(5): 691-701.e5, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31726031

RESUMO

Understanding the role of the microbiota components in either preventing or favoring enteric infections is critical. Here, we report the discovery of a Listeria bacteriocin, Lmo2776, which limits Listeria intestinal colonization. Oral infection of conventional mice with a Δlmo2776 mutant leads to a thinner intestinal mucus layer and higher Listeria loads both in the intestinal content and deeper tissues compared to WT Listeria. This latter difference is microbiota dependent, as it is not observed in germ-free mice. Strikingly, it is phenocopied by pre-colonization of germ-free mice before Listeria infection with Prevotella copri, an abundant gut-commensal bacteria, but not with the other commensals tested. We further show that Lmo2776 targets P. copri and reduces its abundance. Together, these data unveil a role for P.copri in exacerbating intestinal infection, highlighting that pathogens such as Listeria may selectively deplete microbiota bacterial species to avoid excessive inflammation.


Assuntos
Antibacterianos/farmacologia , Bacteriocinas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Listeria monocytogenes/metabolismo , Listeriose/prevenção & controle , Prevotella/crescimento & desenvolvimento , Animais , Feminino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Vida Livre de Germes , Humanos , Inflamação/prevenção & controle , Listeriose/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Prevotella/efeitos dos fármacos
15.
Microbiol Resour Announc ; 8(44)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672743

RESUMO

Here, we report the draft genome sequence of Listeria innocua strain MEZLIS26, isolated from a healthy goat in Flagstaff, Eastern Cape Province, South Africa. The genome was sequenced using the Illumina MiSeq platform and had a length of 2,800,777 bp, with a G+C content of 37.4%, 2,755 coding DNA sequences (CDSs), 49 transfer RNAs (tRNAs), and 4 noncoding RNAs (ncRNAs).

16.
PLoS Pathog ; 15(10): e1008032, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589660

RESUMO

The intracellular pathogen Listeria monocytogenes is distinguished by its ability to invade and replicate within mammalian cells. Remarkably, of the 15 serovars within the genus, strains belonging to serovar 4b cause the majority of listeriosis clinical cases and outbreaks. The Listeria O-antigens are defined by subtle structural differences amongst the peptidoglycan-associated wall-teichoic acids (WTAs), and their specific glycosylation patterns. Here, we outline the genetic determinants required for WTA decoration in serovar 4b L. monocytogenes, and demonstrate the exact nature of the 4b-specific antigen. We show that challenge by bacteriophages selects for surviving clones that feature mutations in genes involved in teichoic acid glycosylation, leading to a loss of galactose from both wall teichoic acid and lipoteichoic acid molecules, and a switch from serovar 4b to 4d. Surprisingly, loss of this galactose decoration not only prevents phage adsorption, but leads to a complete loss of surface-associated Internalin B (InlB),the inability to form actin tails, and a virulence attenuation in vivo. We show that InlB specifically recognizes and attaches to galactosylated teichoic acid polymers, and is secreted upon loss of this modification, leading to a drastically reduced cellular invasiveness. Consequently, these phage-insensitive bacteria are unable to interact with cMet and gC1q-R host cell receptors, which normally trigger cellular uptake upon interaction with InlB. Collectively, we provide detailed mechanistic insight into the dual role of a surface antigen crucial for both phage adsorption and cellular invasiveness, demonstrating a trade-off between phage resistance and virulence in this opportunistic pathogen.


Assuntos
Proteínas de Bactérias/metabolismo , Bacteriófagos/patogenicidade , Parede Celular/metabolismo , Galactose/metabolismo , Listeria monocytogenes/virologia , Proteínas de Membrana/metabolismo , Ácidos Teicoicos/metabolismo , Virulência , Proteínas de Bactérias/genética , Bacteriófagos/genética , Células CACO-2 , Células Hep G2 , Humanos , Listeria monocytogenes/metabolismo , Proteínas de Membrana/genética , Mutação , Sorogrupo
17.
Nature ; 574(7777): 259-263, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31554973

RESUMO

Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain1,2. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)3 as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o'nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles3,4. Dermal fibroblasts and muscle cells derived from patients with Emery-Dreifuss muscular dystrophy that lack functional FHL15 are resistant to CHIKV infection. Furthermore,  CHIKV infection  is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies.


Assuntos
Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Fatores Celulares Derivados do Hospedeiro/metabolismo , Interações Hospedeiro-Patógeno , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas com Domínio LIM/metabolismo , Proteínas Musculares/metabolismo , Animais , Células Cultivadas , Febre de Chikungunya/tratamento farmacológico , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/genética , Vírus Chikungunya/crescimento & desenvolvimento , Feminino , Fibroblastos/virologia , Células HEK293 , Fatores Celulares Derivados do Hospedeiro/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas com Domínio LIM/deficiência , Proteínas com Domínio LIM/genética , Masculino , Camundongos , Proteínas Musculares/deficiência , Proteínas Musculares/genética , Mioblastos/virologia , Vírus O'nyong-nyong/crescimento & desenvolvimento , Vírus O'nyong-nyong/patogenicidade , Ligação Proteica , RNA Viral/biossíntese , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral
19.
J Infect ; 79(4): 322-331, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31376457

RESUMO

BACKGROUND: Listeria monocytogenes-associated endovascular infections are not well characterized. METHODS: Retrospective study of 71 culture-proven cases reported to the French National Reference Center for Listeria from 1993 to 2018. RESULTS: Seventy-one cases were identified: 42 with vascular aneurysms/prosthetic infections, 27 with endocarditis, 2 with both. Fifty-eight were men (82%); median age was 75 years [46-92]; 93% reported co-morbidities (66/71), including 50% with immunosuppressive conditions. Vascular infections consisted of infected aneurysms (68%) or prosthetic graft infections (32%); vascular rupture was reported in 25/42 (60%). Tissue samples grew L. monocytogenes in 98% (43/44) and blood cultures in 64% (27/42). Endocarditis cases involved prosthetic or native valves or intracardiac devices in respectively 62% (18/29), 28% (8/29) and 10% (3/29). Infected valves were aortic (62%, 16/26), mitral (31%, 8/26) or both (8%, 2/26); 38% patients required surgery; 45% displayed heart failure; 17% had concomitant neurolisteriosis. In-hospital mortality in vascular infections was 12% (5/42) and 41% (12/29) for Lm-associated endocarditis. CONCLUSIONS: Endovascular listeriosis is a rare but severe infection. It manifests as vascular infections and endocarditis, mostly in older patients with vascular or cardiac valve prosthetic devices and co-morbidities. Mortality in Lm-associated endocarditis is twice higher than with other pathogens, requiring prompt recognition and treatment.

20.
Science ; 365(6449): 176-180, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31296770

RESUMO

Elevated levels of type I interferon (IFN) during pregnancy are associated with intrauterine growth retardation, preterm birth, and fetal demise through mechanisms that are not well understood. A critical step of placental development is the fusion of trophoblast cells into a multinucleated syncytiotrophoblast (ST) layer. Fusion is mediated by syncytins, proteins deriving from ancestral endogenous retroviral envelopes. Using cultures of human trophoblasts or mouse cells, we show that IFN-induced transmembrane proteins (IFITMs), a family of restriction factors blocking the entry step of many viruses, impair ST formation and inhibit syncytin-mediated fusion. Moreover, the IFN inducer polyinosinic:polycytidylic acid promotes fetal resorption and placental abnormalities in wild-type but not in Ifitm-deleted mice. Thus, excessive levels of IFITMs may mediate the pregnancy complications observed during congenital infections and other IFN-induced pathologies.


Assuntos
Antígenos de Diferenciação/imunologia , Proteínas Reguladoras de Apoptose/imunologia , Fusão Celular , Morte Fetal/etiologia , Interferon Tipo I/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Proteínas de Ligação a RNA/imunologia , Trofoblastos/imunologia , Animais , Feminino , Reabsorção do Feto/imunologia , Produtos do Gene env/imunologia , Humanos , Camundongos , Poli I-C/farmacologia , Gravidez , Proteínas da Gravidez/imunologia , Trofoblastos/efeitos dos fármacos
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