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[PMID]:29253888
[Au] Autor:Norris MH; Heacock-Kang Y; Zarzycki-Siek J; Bluhm AP; McMillan IA; Schweizer HP; Hoang TT
[Ad] Endereço:Department of Microbiology, University of Hawaii at Manoa, Honolulu, HI, United States of America.
[Ti] Título:Burkholderia pseudomallei natural competency and DNA catabolism: Identification and characterization of relevant genes from a constructed fosmid library.
[So] Source:PLoS One;12(12):e0189018, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Burkholderia spp. are genetically and physiologically diverse. Some strains are naturally transformable and capable of DNA catabolism. Burkholderia pseudomallei (Bp) strains 1026b and K96243 and B. thailandensis strain E264 are able to utilize DNA as a sole carbon source for growth, while only strains 1026b and E264 are naturally transformable. In this study, we constructed low-copy broad-host-range fosmid library, containing Bp strain 1026b chromosomal DNA fragments, and employed a novel positive selection approach to identify genes responsible for DNA uptake and DNA catabolism. The library was transferred to non-competent Bp K96243 and B. cenocepacia (Bc) K56-2, harboring chromosomally-inserted FRT-flanked sacB and pheS counter-selection markers. The library was incubated with DNA encoding Flp recombinase, followed by counter-selection on sucrose and chlorinated phenylalanine, to select for clones that took up flp-DNA, transiently expressed Flp, and excised the sacB-pheS cassette. Putative clones that survived the counter-selection were subsequently incubated with gfp-DNA and bacteria were visualized via fluorescent microscopy to confirm natural competency. Fosmid sequencing identified several 1026b genes implicated in DNA uptake, which were validated using chromosomal mutants. One of the naturally competent clones selected in Bc K56-2 enabled Bc, Bp and B. mallei to utilize DNA as a sole carbon source, and all fosmids were used to successfully create mutations in non-naturally-competent B. mallei and Bp strains.
[Mh] Termos MeSH primário: Burkholderia pseudomallei/genética
DNA Bacteriano/metabolismo
Biblioteca Gênica
Genes Bacterianos
Plasmídeos/genética
[Mh] Termos MeSH secundário: Alelos
Cromossomos Bacterianos/genética
Células Clonais
Reprodutibilidade dos Testes
Especificidade da Espécie
Transformação Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189018


  2 / 1777 MEDLINE  
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[PMID]:29240770
[Au] Autor:Allou N; Martinet O; Allyn J; Bouchet B; Jaffar-Bandjee MC; Galas T; Traversier N; Belmonte O
[Ad] Endereço:Réanimation Polyvalente, Centre Hospitalier Universitaire Félix Guyon, Saint Denis, France.
[Ti] Título:Emergence of melioidosis in the Indian Ocean region: Two new cases and a literature review.
[So] Source:PLoS Negl Trop Dis;11(12):e0006018, 2017 Dec.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Melioidosis is a disease caused by bacteria called B. pseudomallei. Infections can develop after contact with standing water. This disease can reach all the organs and especially the lungs. It is associated with a high mortality rate (up to 50%). Melioidosis is endemic in northern Australia and in Southeast Asia. Nevertheless, B. pseudomallei may be endemic in the Indian Ocean region and in Madagascar in particular, so clinicians and microbiologists should consider acute melioidosis as a differential diagnosis in the Indian Ocean region, in particular from Madagascar.
[Mh] Termos MeSH primário: Burkholderia pseudomallei/patogenicidade
Melioidose/diagnóstico
Melioidose/microbiologia
[Mh] Termos MeSH secundário: Adulto
Burkholderia pseudomallei/isolamento & purificação
Grupo com Ancestrais do Continente Europeu
Seres Humanos
Oceano Índico/epidemiologia
Indonésia
Madagáscar
Masculino
Melioidose/epidemiologia
Melioidose/fisiopatologia
Meia-Idade
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171224
[Lr] Data última revisão:
171224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006018


  3 / 1777 MEDLINE  
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[PMID]:28740137
[Au] Autor:Tamigney Kenfack M; Mazur M; Nualnoi T; Shaffer TL; Ngassimou A; Blériot Y; Marrot J; Marchetti R; Sintiprungrat K; Chantratita N; Silipo A; Molinaro A; AuCoin DP; Burtnick MN; Brett PJ; Gauthier C
[Ad] Endereço:Institut de Chimie IC2MP, CNRS-UMR 7285, Équipe Synthèse Organique, Groupe Glycochimie, Université de Poitiers, 4, rue Michel Brunet, Poitiers, 86073, France.
[Ti] Título:Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens.
[So] Source:Nat Commun;8(1):115, 2017 07 24.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. Studies have highlighted the importance of Bp and Bm lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis of seven oligosaccharides as the minimal structures featuring all of the reported acetylation/methylation patterns associated with Bp and Bm LPS O-antigens (OAgs). Our approach is based on the conversion of an L-rhamnose into a 6-deoxy-L-talose residue at a late stage of the synthetic sequence. Using biochemical and biophysical methods, we demonstrate the binding of several Bp and Bm LPS-specific monoclonal antibodies with terminal OAg residues. Mice immunized with terminal disaccharide-CRM197 constructs produced high-titer antibody responses that crossreacted with Bm-like OAgs. Collectively, these studies serve as foundation for the development of novel therapeutics, diagnostics, and vaccine candidates to combat diseases caused by Bp and Bm.Melioidosis and glanders are multifaceted infections caused by gram-negative bacteria. Here, the authors synthesize a series of oligosaccharides that mimic the lipopolysaccharides present on the pathogens' surface and use them to develop novel glycoconjugates for vaccine development.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Antígenos de Bactérias/metabolismo
Burkholderia mallei/metabolismo
Burkholderia pseudomallei/metabolismo
Epitopos/imunologia
Lipopolissacarídeos/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos de Bactérias/genética
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Vacinas Bacterianas/imunologia
Burkholderia mallei/genética
Burkholderia pseudomallei/genética
Feminino
Regulação Bacteriana da Expressão Gênica/fisiologia
Lipopolissacarídeos/química
Lipopolissacarídeos/metabolismo
Melioidose/prevenção & controle
Camundongos
Camundongos Endogâmicos BALB C
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antigens, Bacterial); 0 (Bacterial Proteins); 0 (Bacterial Vaccines); 0 (Epitopes); 0 (Lipopolysaccharides)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-00173-8


  4 / 1777 MEDLINE  
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[PMID]:28934180
[Au] Autor:Mitchell PK; Campbell C; Montgomery MP; Paoline J; Wilbur C; Posivak-Khouly L; Garafalo K; Elrod M; Liu L; Weltman A
[Ti] Título:Notes from the Field: Travel-Associated Melioidosis and Resulting Laboratory Exposures - United States, 2016.
[So] Source:MMWR Morb Mortal Wkly Rep;66(37):1001-1002, 2017 Sep 22.
[Is] ISSN:1545-861X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In mid-July 2016, a Pennsylvania resident aged 15 years who had recently returned from Thailand was treated by a pediatrician for sore throat, fever, and bilateral thigh abscesses at the sites of mosquito bites (Figure). She had traveled to northeast Thailand with nine other teens as part of an 18-day service-oriented trip run by an Ohio-based youth tour company that arranges travel to Thailand for approximately 500 persons annually. This trip included construction and agricultural activities and recreational mud exposures. The patient subsequently developed right inguinal lymphadenopathy and worsening abscesses, which prompted specimen collection for culture on August 25. This specimen was sent to a commercial laboratory in New Jersey, which identified Burkholderia pseudomallei, the causative organism of melioidosis, on August 30. The patient did not experience pneumonia or bacteremia, and recovered fully after 2 weeks of intensive therapy with parenteral ceftazidime and a 6-month outpatient course of eradication therapy with doxycycline.
[Mh] Termos MeSH primário: Burkholderia pseudomallei/isolamento & purificação
Laboratórios
Melioidose/diagnóstico
Exposição Ocupacional
Viagem
[Mh] Termos MeSH secundário: Adolescente
Feminino
Seres Humanos
Tailândia
Estados Unidos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.15585/mmwr.mm6637a8


  5 / 1777 MEDLINE  
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[PMID]:28929273
[Au] Autor:Su J; Sun H; Liu J; Guo Z; Fan G; Gu G; Wang G
[Ad] Endereço:Key Laboratory of Mollisols Agroecology, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Harbin, 150081, China.
[Ti] Título:Complete genome sequence of a novel lytic bacteriophage isolated from Ralstonia solanacearum.
[So] Source:Arch Virol;162(12):3919-3923, 2017 Dec.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:A lytic podophage RSPI1 was isolated from tobacco field soil collected in Fujian Province, South China using host bacterium Ralstonia solanacearum Tb15-14. Whole genome sequencing of this phage was performed using the high-throughput Ion Torrent PGM Sequencer. The complete genome of RSPI1 was 43,211 bp in length with a mean DNA G + C content of 61.5%. A total of 48 open reading frames were identified with lengths ranging from 132 bp to 5,061 bp, of which, 11, 12 and 25 were identified as functional, structural and unknown genes, respectively. A BLAST analysis revealed that this phage genome had a query cover of 78-79% and a highest identity of 84% with four podophages that infect Burkholderia pseudomallei. Two neighbor-joining phylogenetic trees were constructed using phage DNA polymerase I and tail fiber protein sequences and showed that this phage is closely related to Burkholderia phage Bp-AMP1, and also related to several phages that infect Ralstonia solanacearum. These findings indicate that RSPI1 is a novel phage that infects the notorious plant pathogen Ralstonia solanacearum.
[Mh] Termos MeSH primário: Bacteriófagos/classificação
Bacteriófagos/isolamento & purificação
Podoviridae/classificação
Podoviridae/isolamento & purificação
Ralstonia solanacearum/virologia
[Mh] Termos MeSH secundário: Bacteriólise
Bacteriófagos/genética
Bacteriófagos/fisiologia
Composição de Bases
Burkholderia pseudomallei/virologia
China
Genoma Viral
Sequenciamento de Nucleotídeos em Larga Escala
Fases de Leitura Aberta
Filogenia
Podoviridae/genética
Podoviridae/fisiologia
Análise de Sequência de DNA
Homologia de Sequência
Microbiologia do Solo
Tabaco/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3555-2


  6 / 1777 MEDLINE  
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[PMID]:28827286
[Au] Autor:Gamage AM; Lee KO; Gan YH
[Ad] Endereço:Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; and.
[Ti] Título:Anti-Cancer Drug HMBA Acts as an Adjuvant during Intracellular Bacterial Infections by Inducing Type I IFN through STING.
[So] Source:J Immunol;199(7):2491-2502, 2017 Oct 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The anti-proliferative agent hexamethylene bisacetamide (HMBA) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. Recently, HMBA has also been shown to trigger HIV transcription from latently infected cells, via a CDK9/HMBA inducible protein-1 dependent process. However, the effect of HMBA on the immune response has not been explored. We observed that pretreatment of human peripheral blood mononuclear cells with HMBA led to a markedly increased production of IL-12 and IFN-γ, but not of TNF-α, IL-6, and IL-8 upon subsequent infection with and HMBA treatment was also associated with better intracellular bacterial control. HMBA significantly improved IL-12p70 production from CD14 monocytes during infection partly via the induction of type I IFN in these cells, which primed an increased transcription of the p35 subunit of IL-12p70 during infection. HMBA also increased early type I IFN transcription in human monocytic and epithelial cell lines, but this was surprisingly independent of its previously reported effects on positive transcription elongation factor b and HMBA inducible protein-1. Instead, the effect of HMBA was downstream of a calcium influx, and required the pattern recognition receptor and adaptor STING but not cGAS. Our work therefore links the STING-IRF3 axis to enhanced IL-12 production and intracellular bacterial control in primary monocytes. This raises the possibility that HMBA or related small molecules may be explored as therapeutic adjuvants to improve disease outcomes during intracellular bacterial infections.
[Mh] Termos MeSH primário: Acetamidas/farmacologia
Adjuvantes Imunológicos
Interferon Tipo I/biossíntese
Leucócitos Mononucleares/efeitos dos fármacos
Leucócitos Mononucleares/microbiologia
Proteínas de Membrana/metabolismo
[Mh] Termos MeSH secundário: Acetamidas/uso terapêutico
Burkholderia pseudomallei/efeitos dos fármacos
Burkholderia pseudomallei/imunologia
Linhagem Celular
Células Cultivadas
Citoplasma/imunologia
Citoplasma/microbiologia
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/imunologia
Células Epiteliais/microbiologia
Seres Humanos
Fator Regulador 3 de Interferon/metabolismo
Interferon Tipo I/genética
Interferon Tipo I/imunologia
Interferon gama/biossíntese
Interferon gama/imunologia
Interleucina-12/biossíntese
Interleucina-12/imunologia
Interleucina-6/biossíntese
Interleucina-6/imunologia
Interleucina-8/biossíntese
Interleucina-8/imunologia
Leucócitos Mononucleares/imunologia
Proteínas de Membrana/imunologia
Nucleotidiltransferases/genética
Nucleotidiltransferases/metabolismo
Salmonella enterica/efeitos dos fármacos
Salmonella enterica/imunologia
Transdução de Sinais
Fator de Necrose Tumoral alfa/biossíntese
Fator de Necrose Tumoral alfa/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetamides); 0 (Adjuvants, Immunologic); 0 (IL6 protein, human); 0 (IRF3 protein, human); 0 (Interferon Regulatory Factor-3); 0 (Interferon Type I); 0 (Interleukin-6); 0 (Interleukin-8); 0 (MPYS protein, human); 0 (Membrane Proteins); 0 (Tumor Necrosis Factor-alpha); 187348-17-0 (Interleukin-12); 82115-62-6 (Interferon-gamma); EC 2.7.7.- (MB21D1 protein, human); EC 2.7.7.- (Nucleotidyltransferases); LA133J59VU (hexamethylene bisacetamide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1602162


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[PMID]:28820897
[Au] Autor:See JX; Chandramathi S; Abdulla MA; Vadivelu J; Shankar EM
[Ad] Endereço:Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
[Ti] Título:Persistent infection due to a small-colony variant of Burkholderia pseudomallei leads to PD-1 upregulation on circulating immune cells and mononuclear infiltration in viscera of experimental BALB/c mice.
[So] Source:PLoS Negl Trop Dis;11(8):e0005702, 2017 Aug.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes. Moreover, recurrence rates in melioidosis patients can be up to ~13% despite appropriate antibiotic therapy, suggestive of bacterial persistence and inefficacy of antibiotic regimens. The mechanisms behind bacterial persistence in the host remain unclear, and hence understanding host immunity during persistent B. pseudomallei infections may help designing potential immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: A persistent infection was generated using a small-colony variant (SCV) and a wild-type (WT) B. pseudomallei in BALB/c mice via intranasal administration. Infected mice that survived for >60 days were sacrificed. Lungs, livers, spleens, and peripheral blood mononuclear cells were harvested for experimental investigations. Histopathological changes of organs were observed in the infected mice, suggestive of successful establishment of persistent infections. Moreover, natural killer (NK) cell frequency was increased in SCV- and WT-infected mice. We observed programmed death-1 (PD-1) upregulation on B cells of SCV- and WT-infected mice. Interestingly, PD-1 upregulation was only observed on NK cells and monocytes of SCV-infected mice. In contrast, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) downregulation was seen on NK cells of WT-infected mice, and on monocytes of SCV- and WT-infected mice. CONCLUSIONS/SIGNIFICANCE: The SCV and the WT of B. pseudomallei distinctly upregulated PD-1 expression on B cells, NK cells, and monocytes to dampen host immunity, which likely facilitates bacterial persistence. PD-1/PD-L1 pathway appears to play an important role in the persistence of B. pseudomallei in the host.
[Mh] Termos MeSH primário: Estruturas Animais/patologia
Burkholderia pseudomallei/patogenicidade
Melioidose/patologia
Receptor de Morte Celular Programada 1/análise
[Mh] Termos MeSH secundário: Animais
Burkholderia pseudomallei/crescimento & desenvolvimento
Doença Crônica
Modelos Animais de Doenças
Histocitoquímica
Células Matadoras Naturais/química
Camundongos Endogâmicos BALB C
Monócitos/química
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pdcd1 protein, mouse); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170901
[Lr] Data última revisão:
170901
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005702


  8 / 1777 MEDLINE  
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[PMID]:28764662
[Au] Autor:Kahandawaarachchi ICI; Premawansa GS; Warnasuriya W; Dassanayake M; Corea E
[Ad] Endereço:North Colombo Teaching Hospital, Ragama, Sri Lanka. isurucik@gmail.com.
[Ti] Título:A case report of co-infection of Melioidosis and cutaneous Leishmaniasis.
[So] Source:BMC Infect Dis;17(1):533, 2017 Aug 01.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Leishmaniasis and melioidosis are frequently reported from the North Central Province of Sri Lanka. However, only one case of co-infection of the two diseases has been reported to date over the world. This is a case report of a patient who had co-infection with cutaneous leishmaniasis and melioidosis and was successfully treated and recovered from the illness. CASE PRESENTATION: A 61 year old female patient with diabetes mellitus presented with fever for one month's duration and was found to have hepatosplenomegaly and an ulcer over the left arm. She had elevated inflammatory markers and blood culture grew Burkholderia pseudomallei and serum was highly positive for melioidosis antibodies. A slit skin smear of the ulcer showed Leishmania amastigotes. CONCLUSION: Melioidosis and leishmaniasis are emerging infectious diseases in endemic countries and can be severe. The high prevalence rates in Sri Lanka should keep the treating physicians' threshold for suspicion low for these two diseases.
[Mh] Termos MeSH primário: Leishmaniose Cutânea/etiologia
Melioidose/etiologia
[Mh] Termos MeSH secundário: Abscesso Abdominal/tratamento farmacológico
Burkholderia pseudomallei/isolamento & purificação
Ceftazidima/uso terapêutico
Coinfecção
Feminino
Seres Humanos
Leishmania/patogenicidade
Leishmaniose Cutânea/tratamento farmacológico
Melioidose/tratamento farmacológico
Meia-Idade
Sri Lanka
Tienamicinas/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Thienamycins); 9M416Z9QNR (Ceftazidime); FV9J3JU8B1 (meropenem)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2639-7


  9 / 1777 MEDLINE  
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[PMID]:28760929
[Au] Autor:Whiteley L; Meffert T; Haug M; Weidenmaier C; Hopf V; Bitschar K; Schittek B; Kohler C; Steinmetz I; West TE; Schwarz S
[Ad] Endereço:Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tuebingen, Germany.
[Ti] Título:Entry, Intracellular Survival, and Multinucleated-Giant-Cell-Forming Activity of Burkholderia pseudomallei in Human Primary Phagocytic and Nonphagocytic Cells.
[So] Source:Infect Immun;85(10), 2017 Oct.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human pathogen and the related species are facultative intracellular bacteria characterized by the ability to escape into the cytosol of the host cell and to stimulate the formation of multinucleated giant cells (MNGCs). MNGC formation is induced via an unknown mechanism by bacterial type VI secretion system 5 (T6SS-5), which is an essential virulence factor in both species. Despite the vital role of the intracellular life cycle in the pathogenesis of the bacteria, the range of host cell types permissive for initiation and completion of the intracellular cycle is poorly defined. In the present study, we used several different types of human primary cells to evaluate bacterial entry, intracellular survival, and MNGC formation. We report the capacity of to enter, efficiently replicate in, and mediate MNGC formation of vein endothelial and bronchial epithelial cells, indicating that the T6SS-5 is important in the host-pathogen interaction in these cells. Furthermore, we show that invades fibroblasts and keratinocytes and survives inside these cells as well as in monocyte-derived macrophages and neutrophils for at least 17 h postinfection; however, MNGC formation is not induced in these cells. In contrast, infection of mixed neutrophils and RAW264.7 macrophages with stimulated the formation of heterotypic MNGCs in a T6SS-5-dependent manner. In summary, the ability of the bacteria to enter and survive as well as induce MNGC formation in certain host cells may contribute to the pathogenesis observed in infection.
[Mh] Termos MeSH primário: Burkholderia pseudomallei/fisiologia
Células Gigantes/microbiologia
Interações Hospedeiro-Patógeno
Macrófagos/microbiologia
Fagócitos/microbiologia
[Mh] Termos MeSH secundário: Animais
Brônquios/citologia
Brônquios/microbiologia
Burkholderia pseudomallei/crescimento & desenvolvimento
Burkholderia pseudomallei/patogenicidade
Linhagem Celular
Células Cultivadas
Citosol/microbiologia
Células Endoteliais/microbiologia
Células Epiteliais/microbiologia
Fibroblastos/microbiologia
Seres Humanos
Queratinócitos/microbiologia
Camundongos
Neutrófilos/microbiologia
Sistemas de Secreção Tipo VI/metabolismo
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Type VI Secretion Systems)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE


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[PMID]:28719324
[Au] Autor:Sengyee S; Saiprom N; Paksanont S; Limmathurotsakul D; Wuthiekanun V; Chantratita N
[Ad] Endereço:Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
[Ti] Título:Susceptibility of Clinical Isolates of to a Lipid A Biosynthesis Inhibitor.
[So] Source:Am J Trop Med Hyg;97(1):62-67, 2017 Jul.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:is the causative agent of melioidosis, a serious infection associated with high mortality and relapse. Current antimicrobial therapy using ceftazidime (CAZ) is often ineffective. Inhibitors of LpxC, the enzyme responsible for lipid A biosynthesis, have potential antimicrobial activity against several Gram-negative bacteria in vivo, but their activity against is unclear. Herein, we investigated the susceptibility of clinical isolates to LpxC-4, an LpxC inhibitor, and LpxC-4 in combination with CAZ. Time-kill assays for bactericidal activity were conducted for K96243, revealing growth inhibition and bactericidal effect at LpxC-4 concentrations of 2 µg/mL and 4 µg/mL, respectively. No significant synergistic effect was observed with the combination of LpxC-4 and CAZ. LpxC-4 susceptibility was tested on three groups of clinical isolates:1) CAZ- and trimethoprim-sulfamethoxazole (SXT)-susceptible ( = 71), 2) CAZ-resistant ( = 14), and 3) SXT-resistant ( = 23) isolates, by broth microdilution. The minimum concentration of LpxC-4 required to inhibit the growth of 90% of organisms was 2 µg/mL for all isolates. The median minimum inhibitory concentration of both the CAZ/SXT-susceptible and CAZ-resistant groups was 1 µg/mL (interquartile range [IQR] = 1-2 µg/mL), compared with 2 µg/mL (IQR = 2-4 µg/mL) for the SXT-resistant group. Cell morphology was observed after drug exposure by immunofluorescent staining, and a change from rod-shaped to cell wall-defective spherical cells was observed in surviving bacteria. LpxC-4 is a potent bactericidal agent against and warrants further testing as a new antibiotic to treat melioidosis.
[Mh] Termos MeSH primário: Aciltransferases/fisiologia
Antibacterianos/uso terapêutico
Proteínas de Bactérias/fisiologia
Burkholderia pseudomallei/efeitos dos fármacos
Ceftazidima/uso terapêutico
Farmacorresistência Bacteriana/efeitos dos fármacos
Melioidose/tratamento farmacológico
[Mh] Termos MeSH secundário: Inibidores Enzimáticos/uso terapêutico
Seres Humanos
Melioidose/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Enzyme Inhibitors); 9M416Z9QNR (Ceftazidime); EC 2.3.- (Acyltransferases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171118
[Lr] Data última revisão:
171118
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0858



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