A Superoxide Dismutase C Mutant of
            <i>Haemophilus ducreyi</i>
            Is Virulent in Human Volunteers

Bong, Cliffton T. H.; Fortney, Kate R.; Katz, Barry P.; Hood, Antoinette F.; Mateo, Lani R. San; Kawula, Thomas H.; Spinola, Stanley M.

doi:10.1128/iai.70.3.1367-1371.2002

Cited by 18 publications

(9 citation statements)

References 42 publications

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“…Hfq is required for the optimal production of SodC during stationary phase in B. abortus (30), and SodC-defective strains of B. abortus (30) or S. enterica (2) are affected in virulence. Nevertheless, this is not true in all bacteria, since the lack of SodC in Haemophilus ducreyi has no consequence on the virulence (13). We showed that the sodC mutant did not lose resistance against external superoxides.…”

Section: Discussionmentioning

confidence: 78%

Proteomic Alterations Explain Phenotypic Changes in Sinorhizobium meliloti Lacking the RNA Chaperone Hfq

et al. 2010

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The ubiquitous bacterial RNA-binding protein Hfq is involved in stress resistance and pathogenicity. In Sinorhizobium meliloti, Hfq is essential for the establishment of symbiosis with Medicago sativa and for nitrogen fixation. A proteomic analysis identifies 55 proteins with significantly affected expression in the hfq mutant; most of them are involved in cell metabolism or stress resistance. Important determinants of oxidative stress resistance, such as CysK, Gsh, Bfr, SodC, KatB, KatC, and a putative peroxiredoxine (SMc00072), are downregulated in the hfq mutant. The hfq mutant is affected for H 2 O 2 , menadione, and heat stress resistance. Part of these defects could result from the reductions of rpoE1, rpoE2, rpoE3, and rpoE4 expression levels in the hfq mutant. Some proteins required for efficient symbiosis are reduced in the hfq mutant, contributing to the drastic defect in nodulation observed in this mutant.Gene expression in bacteria is regulated by a wide diversity of mechanisms, including alternative sigma factors, transcriptional regulatory proteins, attenuation mechanisms (including riboswitches) (15), and translational and posttranslational regulations (37). The interplay of central regulatory proteins and alternative sigma factors allows the creation of complex regulatory networks modulating transcription (4).Compared to transcription regulation, the mechanisms affecting the regulation of translation are less understood. Studies dedicated to translation regulation have increased over the past few years (55,76,77). An important development has been the recognition of small regulatory RNAs (sRNAs) that have emerged as crucial actors of translation regulation. In enterobacteria, most sRNAs require Hfq to complex with their targets. Hfq is an RNA chaperone necessary for the pairing of sRNAs with mRNAs (40). Furthermore, Hfq affects translation efficiency by allowing the polyadenylation of specific mRNAs (44). Thus, Hfq is a central actor in translation regulation (72). Hfq is also able to affect transcription, directly by coupling with RNA polymerase (67) or indirectly via its action on sRNAs modulating translation of sigma factors (19,32,69).Due to its central role, hfq inactivation results in a pleiotropic phenotype in enterobacteria and Brucella abortus, including growth defects, stress susceptibility, and altered pathogenicity (56,65,76). Our accompanying study shows that loss of hfq impairs the ability of Sinorhizobium meliloti to establish a nitrogen-fixing symbiosis with its legume host, Medicago sativa. S. meliloti faces numerous stresses during the course of invading the developing root nodules and colonizing the plant cells (21,22,35,46,62). Bacterial abilities to resist and adapt to these stresses are of crucial importance for the symbiosis. Oxidative stress has been the most intensively investigated stress that S. meliloti must withstand and appears as a key factor for bacterium-plant cell interaction. To cope with oxidative stress, S. meliloti cells posses a detoxification system involvi...

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Section: Discussionmentioning

confidence: 78%

Proteomic Alterations Explain Phenotypic Changes in Sinorhizobium meliloti Lacking the RNA Chaperone Hfq

et al. 2010

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“…sodC encodes a periplasmic copper-zinc superoxide dismutase, hhdB is involved in the secretion of hemolysin, and ompP2A encodes a porin (42)(43)(44). Thus, downregulation of the expression of OMPs or secreted proteins by CpxRA does not necessarily imply a role in virulence.…”

Section: Transcriptome Analysismentioning

confidence: 99%

Activation of CpxRA in Haemophilus ducreyi Primarily Inhibits the Expression of Its Targets, Including Major Virulence Determinants

et al. 2013

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Haemophilus ducreyi causes chancroid, a genital ulcer disease that facilitates the transmission of human immunodeficiency virus type 1. In humans, H. ducreyi is surrounded by phagocytes and must adapt to a hostile environment to survive. To sense and respond to environmental cues, bacteria frequently use two-component signal transduction (2CST) systems. The only obvious 2CST system in H. ducreyi is CpxRA; CpxR is a response regulator, and CpxA is a sensor kinase. Previous studies by Hansen and coworkers showed that CpxR directly represses the expression of dsrA, the lspB-lspA2 operon, and the flp operon, which are required for virulence in humans. They further showed that CpxA functions predominantly as a phosphatase in vitro to maintain the expression of virulence determinants. Since a cpxA mutant is avirulent while a cpxR mutant is fully virulent in humans, CpxA also likely functions predominantly as a phosphatase in vivo. To better understand the role of H. ducreyi CpxRA in controlling virulence determinants, here we defined genes potentially regulated by CpxRA by using RNA-Seq. Activation of CpxR by deletion of cpxA repressed nearly 70% of its targets, including seven established virulence determinants. Inactivation of CpxR by deletion of cpxR differentially regulated few genes and increased the expression of one virulence determinant. We identified a CpxR binding motif that was enriched in downregulated but not upregulated targets. These data reinforce the hypothesis that CpxA phosphatase activity plays a critical role in controlling H. ducreyi virulence in vivo. Characterization of the downregulated genes may offer new insights into pathogenesis.

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“…This hypothesis is supported by several studies demonstrating that mutants deficient in Cu,Zn SOD production (sodC mutants) are attenuated in animal models for disease. However, the role that Cu,Zn SOD plays in bacterial virulence is ambiguous-it clearly contributes to disease in some organisms (20,75), but not in others (9,64). This discrepancy may be due to differences in experimental models.…”

Section: Discussionmentioning

confidence: 99%

Interaction between Leukotoxin and Cu,Zn Superoxide Dismutase in Aggregatibacter actinomycetemcomitans

et al. 2007

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Aggregatibacter (Actinobacillus) actinomycetemcomitans is a gram-negative oral pathogen that is the etiologic agent of localized aggressive periodontitis and systemic infections. A. actinomycetemcomitans produces leukotoxin (LtxA), which is a member of the RTX (repeats in toxin) family of secreted bacterial toxins and is known to target human leukocytes and erythrocytes. To better understand how LtxA functions as a virulence factor, we sought to detect and study potential A. actinomycetemcomitans proteins that interact with LtxA. We found that Cu,Zn superoxide dismutase (SOD) interacts specifically with LtxA. Cu,Zn SOD was purified from A. actinomycetemcomitans to homogeneity and remained enzymatically active. Purified Cu,Zn SOD allowed us to isolate highly specific anti-Cu,Zn SOD antibody and this antibody was used to further confirm protein interaction. Cu,Zn SOD-deficient mutants displayed decreased survival in the presence of reactive oxygen and nitrogen species and could be complemented with wild-type Cu,Zn SOD in trans. We suggest that A. actinomycetemcomitans Cu,Zn SOD may protect both bacteria and LtxA from reactive species produced by host inflammatory cells during disease. This is the first example of a protein-protein interaction involving a bacterial Cu,Zn SOD.

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A Superoxide Dismutase C Mutant of Haemophilus ducreyi Is Virulent in Human Volunteers

Cited by 18 publications

References 42 publications

Proteomic Alterations Explain Phenotypic Changes in Sinorhizobium meliloti Lacking the RNA Chaperone Hfq

Proteomic Alterations Explain Phenotypic Changes in Sinorhizobium meliloti Lacking the RNA Chaperone Hfq

Activation of CpxRA in Haemophilus ducreyi Primarily Inhibits the Expression of Its Targets, Including Major Virulence Determinants

Interaction between Leukotoxin and Cu,Zn Superoxide Dismutase in Aggregatibacter actinomycetemcomitans

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