An extracellular zinc metalloprotease gene of Burkholderia cepacia

Corbett, Clare; Burtnick, Mary N.; Kooi, Cora; Woods, Donald E.; Sokol, Pamela A.

doi:10.1099/mic.0.26243-0

Cited by 68 publications

(86 citation statements)

References 55 publications

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“…Most clinical strains of P. aeruginosa produce elastase, a zinc metalloprotease that is implicated in the pathogenesis of infections related to these organisms. Indeed, numerous other examples of proteases and aminopeptidases that are linked to virulence have been highlighted (Coffey et al, 2000;Corbett et al, 2003;Feil et al, 2005;Hidalgo-Grass et al, 2006;Kooi et al, 2006;Song et al, 2004;Spratt et al, 1995). Dipeptidyl aminopeptidase activity has previously been implicated in the virulence of Porphyromonas gingivalis (Kumagai et al, 2000).…”

Section: Gly-glumentioning

confidence: 99%

Genetic analysis of genes involved in dipeptide metabolism and cytotoxicity in Pseudomonas aeruginosa PAO1

et al. 2008

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The dipeptide transport operon in bacteria comprises genes for the transport and metabolism of amino acids and dipeptides, as well as haem and haem precursors such as aminolaevulinic acid. Such nutrient and mineral sources are vital for bacteria to survive in and colonize a range of niches. In silico analysis of the dipeptide transport systems in sequenced Pseudomonas species identified the presence of two genes in P. aeruginosa strains that were absent in other sequenced pseudomonads. These genes encode a putative metallopeptidase, PA4498, and a putative transcriptional regulator, PA4499. Proteomic profiling of wild-type PAO1 and a PA4499 mutant strain indicated that PA4499 negatively regulated the putative peptidase, PA4498. Transcriptional fusion analysis verified that expression of PA4498 (mdpA, metallo-dipeptidase aeruginosa) was negatively regulated by the downstream putative transcriptional regulator PA4499 (psdR, Pseudomonas dipeptide regulator). Transcriptional fusion analysis also showed that the dppABCDF operon was under the negative control of psdR. Functional genomic analysis of mdpA indicated that it is required for the metabolism of a range of dipeptides and that it contributes to the cytotoxicity of PAO1 on an epithelial cell line.

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Section: Gly-glumentioning

confidence: 99%

Genetic analysis of genes involved in dipeptide metabolism and cytotoxicity in Pseudomonas aeruginosa PAO1

et al. 2008

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“…Also, several genes are present that may mediate resistance to reactive oxygen species and enable LB400 to survive within intracellular environments. Although LB400 encodes three phospholipase homologs and an LasA-type protease, its repertoire of phospholipases, proteases, and collagenases, which have been implicated in Burkholderia virulence (20,51), is limited. LB400 also lacks homologs of the B. cenocepacia cable pilus, a defining pathogenic feature of one of the most problematic strains in cystic fibrosis infection (12).…”

Section: Genetic Factors Indicating the Ecological Niche Of B Xenovomentioning

confidence: 99%

Burkholderia xenovorans LB400 harbors a multi-replicon, 9.73-Mbp genome shaped for versatility

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Denef

Konstantinidis

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

325

280

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Burkholderia xenovorans LB400 (LB400), a well studied, effective polychlorinated biphenyl-degrader, has one of the two largest known bacterial genomes and is the first nonpathogenic Burkholderia isolate sequenced. From an evolutionary perspective, we find significant differences in functional specialization between the three replicons of LB400, as well as a more relaxed selective pressure for genes located on the two smaller vs. the largest replicon. High genomic plasticity, diversity, and specialization within the Burkholderia genus are exemplified by the conservation of only 44% of the genes between LB400 and Burkholderia cepacia complex strain 383. Even among four B. xenovorans strains, genome size varies from 7.4 to 9.73 Mbp. The latter is largely explained by our findings that >20% of the LB400 sequence was recently acquired by means of lateral gene transfer. Although a range of genetic factors associated with in vivo survival and intercellular interactions are present, these genetic factors are likely related to niche breadth rather than determinants of pathogenicity. The presence of at least eleven ''central aromatic'' and twenty ''peripheral aromatic'' pathways in LB400, among the highest in any sequenced bacterial genome, supports this hypothesis. Finally, in addition to the experimentally observed redundancy in benzoate degradation and formaldehyde oxidation pathways, the fact that 17.6% of proteins have a better LB400 paralog than an ortholog in a different genome highlights the importance of gene duplication and repeated acquirement, which, coupled with their divergence, raises questions regarding the role of paralogs and potential functional redundancies in large-genome microbes.genomics ͉ niche adaptation ͉ evolution ͉ biodegradation ͉ redundancy

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“…The chronic agar bead model (Cash et al, 1979) originally developed to mimic P. aeruginosa respiratory infections in CF patients has been used to demonstrate that iron acquisition via the siderophore ornibactin is necessary for persistence of B. cenocepacia chronic infections (Sokol et al, , 2000. Recently, we have used this model to demonstrate that a zinc metalloprotease contributes to the virulence of some strains of B. cenocepacia (Corbett et al, 2003). A modified agar bead model in mice has been used to compare invasiveness of members of the B. cepacia complex during acute infections (Cieri et al, 2002) and to demonstrate that Type III secretion is important for virulence (Tomich et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

The CepIR quorum-sensing system contributes to the virulence of Burkholderia cenocepacia respiratory infections

et al. 2003

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The cepIR genes encode an N-acyl homoserine lactone (AHL)-dependent quorum-sensing system consisting of an AHL synthase that directs the synthesis of N-octanoyl-L-homoserine lactone (OHL) and N-hexanoyl-L-homoserine lactone and a transcriptional regulator. The virulence of cepIR mutants was examined in two animal models. Rats were infected with agar beads containing Burkholderia cenocepacia K56-2, K56-I2 (cepI : : Tp r ) or K56-R2 (cepR : : Tn5-OT182). At 10 days post-infection, the extent of lung histopathological changes was significantly lower in lungs infected with K56-I2 or K56-R2 compared to the parent strain. Intranasal infections were performed in Cftr ("/") mice and their wild-type siblings. K56-2 was more virulent in both groups of mice. K56-I2 was the least virulent strain and was not invasive in the Cftr ("/") mice. OHL was readily detected in lung homogenates from Cftr ("/") mice infected with K56-2 but was only detected at levels slightly above background in a few mice infected with K56-I2. Lung homogenates from mice infected with K56-2 had significantly higher levels of the inflammatory mediators murine macrophage inflammatory protein-2, KC/N51, interleukin-1b and interleukin-6 than those from K56-I2-infected animals. These studies indicate that a functional CepIR quorum-sensing system contributes to the severity of B. cenocepacia infections. A zinc metalloprotease gene (zmpA) was shown to be regulated by CepR and may be one of the factors that accounts for the difference in virulence between the cepI mutant and the parent strain.

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An extracellular zinc metalloprotease gene of Burkholderia cepacia

Cited by 68 publications

References 55 publications

Genetic analysis of genes involved in dipeptide metabolism and cytotoxicity in Pseudomonas aeruginosa PAO1

Genetic analysis of genes involved in dipeptide metabolism and cytotoxicity in Pseudomonas aeruginosa PAO1

Burkholderia xenovorans LB400 harbors a multi-replicon, 9.73-Mbp genome shaped for versatility

The CepIR quorum-sensing system contributes to the virulence of Burkholderia cenocepacia respiratory infections

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