Burkholderia cenocepacia J2315 acyl carrier protein: A potential target for antimicrobials' development?

Sousa, Sílvia A.; Almeida, Filipe; Meirinhos-Soares, Luís; Wopperer, Julia; Schwager, Stephan; Eberl, Leo; Leitão, Jorge H.

doi:10.1016/j.micpath.2008.08.002

Cited by 25 publications

(32 citation statements)

References 25 publications

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“…Images were taken at ϫ1,000 magnification. Nematodes were imaged after immobilization with sodium azide at ϫ500 magnification, according to previously described methods (20).…”

Section: Methodsmentioning

confidence: 99%

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MtvR Is a Global Small Noncoding Regulatory RNA in Burkholderia cenocepacia

et al. 2013

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Burkholderia cenocepacia J2315 is a highly epidemic and transmissible clinical isolate of the Burkholderia cepacia complex (Bcc), a group of bacteria causing life-threatening respiratory infections among cystic fibrosis patients. This work describes the functional analysis of the 136-nucleotide (nt)-long MtvR small noncoding RNA (sRNA) from the Bcc member B. cenocepacia J2315, with homologues restricted to the genus Burkholderia. Bioinformatic target predictions revealed a total of 309 mRNAs to be putative MtvR targets. The mRNA levels corresponding to 17 of 19 selected genes were found to be affected when MtvR was either overexpressed or silenced. Analysis of the interaction between MtvR and the hfq mRNA, one of its targets, showed that the sRNA binds exclusively to the 5= untranslated region (UTR) of the hfq mRNA. This interaction resulted in decreased protein synthesis, suggesting a negative regulatory effect of MtvR on the RNA chaperone Hfq. Bacterial strains with MtvR silenced or overexpressed exhibited pleiotropic phenotypes related to growth and survival after several stresses, swimming and swarming motilities, biofilm formation, resistance to antibiotics, and ability to colonize and kill the nematode Caenorhabditis elegans. Together, the results indicate that the MtvR sRNA is a major posttranscriptional regulator in B. cenocepacia.

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“…Images were taken at ϫ1,000 magnification. Nematodes were imaged after immobilization with sodium azide at ϫ500 magnification, according to previously described methods (20).…”

Section: Methodsmentioning

confidence: 99%

“…Nematode-killing assays and bacterial colonization of the digestive tracts of the nematodes were performed using Caenorhabditis elegans DH26, as previously described (20). The results are the mean values of triplicates from at least 3 independent experiments (n ϭ 1,250 Ϯ 25 worms).…”

Section: Methodsmentioning

confidence: 99%

MtvR Is a Global Small Noncoding Regulatory RNA in Burkholderia cenocepacia

et al. 2013

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“…1B), disruption of which results in a nonmotile strain that is avirulent in the mouse agar bead model of infection (165), and cable pili, which are required for binding to cytokeratin 13 on epithelial cells (139) and killing of human airway epithelial cells ex vivo (32). Additionally, Sousa et al (152) have shown that a B. cenocepacia mutant strain lacking an acyl carrier protein (ACP) has alterations in fatty acid content and increased cell surface hydrophobicity. This mutant strain has a greater ability to form biofilms in vitro but has decreased pathogenicity in the C. elegans infection model (152).…”

Section: Virulence Determinants Of B Cenocepaciamentioning

confidence: 99%

A Decade of Burkholderia cenocepacia Virulence Determinant Research

2010

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The Burkholderia cepacia complex (Bcc) is a group of genetically related environmental bacteria that can cause chronic opportunistic infections in patients with cystic fibrosis (CF) and other underlying diseases. These infections are difficult to treat due to the inherent resistance of the bacteria to antibiotics. Bacteria can spread between CF patients through social contact and sometimes cause cepacia syndrome, a fatal pneumonia accompanied by septicemia. Burkholderia cenocepacia has been the focus of attention because initially it was the most common Bcc species isolated from patients with CF in North America and Europe. Today, B. cenocepacia, along with Burkholderia multivorans, is the most prevalent Bcc species in patients with CF. Given the progress that has been made in our understanding of B. cenocepacia over the past decade, we thought that it was an appropriate time to review our knowledge of the pathogenesis of B. cenocepacia, paying particular attention to the characterization of virulence determinants and the new tools that have been developed to study them. A common theme emerging from these studies is that B. cenocepacia establishes chronic infections in immunocompromised patients, which depend more on determinants mediating host niche adaptation than those involved directly in host cells and tissue damage.

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“…This suggests that an ACPS, or an additional Sfp-type PPTase with broad substrate specificity, is encoded by the B. cenocepacia genome. TBLASTN analysis of the genomes of B. cenocepacia strains HI2424 and J2315 reveals that they encode an ACPS [in fact, chromosome 1 of strain J2315 contains a duplication of 57 kb which gives rise to two identical copies of an acpS orthologue: BCAL1009 and BCAL2861 (Holden et al, 2009;Sousa et al, 2008)]. Furthermore, there are no additional Sfp-type PPTases encoded by the genome of strain J2315.…”

Section: Discussionmentioning

confidence: 99%

The pobA gene of Burkholderia cenocepacia encodes a Group I Sfp-type phosphopantetheinyltransferase required for biosynthesis of the siderophores ornibactin and pyochelin

et al. 2011

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The opportunistic pathogen Burkholderia cenocepacia produces the siderophores ornibactin and pyochelin under iron-restricted conditions. Biosynthesis of both siderophores requires the involvement of non-ribosomal peptide synthetases (NRPSs). Using a transposon containing the lacZ reporter gene, two B. cenocepacia mutants were isolated which were deficient in siderophore production. Mutant IW10 was shown to produce normal amounts of ornibactin but only trace amounts of pyochelin, whereas synthesis of both siderophores was abolished in AHA27. Growth of AHA27, but not IW10, was inhibited under iron-restricted conditions. In both mutants, the transposon had integrated into the pobA gene, which encodes a polypeptide exhibiting similarity to the Sfp-type phosphopantetheinyltransferases (PPTases). These enzymes are responsible for activation of NRPSs by the covalent attachment of the 4′-phosphopantetheine (P-pant) moiety of coenzyme A. Previously characterized PPTase genes from other bacteria were shown to efficiently complement both mutants for siderophore production when provided in trans. The B. cenocepacia pobA gene was also able to efficiently complement an Escherichia coli entD mutant for production of the siderophore enterobactin. Using mutant IW10, in which the lacZ gene carried by the transposon is inserted in the same orientation as pobA, it was shown that pobA is not appreciably iron-regulated. Finally, we confirmed that Sfp-type bacterial PPTases can be subdivided into two distinct groups, and we present the amino acid signature sequences which characterize each of these groups.

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Burkholderia cenocepacia J2315 acyl carrier protein: A potential target for antimicrobials' development?

Cited by 25 publications

References 25 publications

MtvR Is a Global Small Noncoding Regulatory RNA in Burkholderia cenocepacia

MtvR Is a Global Small Noncoding Regulatory RNA in Burkholderia cenocepacia

A Decade of Burkholderia cenocepacia Virulence Determinant Research

The pobA gene of Burkholderia cenocepacia encodes a Group I Sfp-type phosphopantetheinyltransferase required for biosynthesis of the siderophores ornibactin and pyochelin

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