YjbH Solubility Controls Spx in Staphylococcus aureus: Implication for MazEF Toxin-Antitoxin System Regulation

Panasenko, Olesya O.; Bezrukov, Fedor; Komarynets, Olga; Renzoni, Adriana

doi:10.3389/fmicb.2020.00113

Cited by 13 publications

(17 citation statements)

References 57 publications

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“…In our RNA seq analysis, we found that the expression of stress regulators spxA and sigB, including SigBspecific genes, were downregulated. YjbH is involved in the proteolysis of Spx, a stress regulator required for oxidative stress tolerance [18,19,21,36]. In the absence of YjbH, Spx is accumulated, which represses its own expression [36].…”

Section: Discussionmentioning

confidence: 99%

“…Pathogenicity was restored by the introduction of the yjbIH operon and not of the yjbI gene [14], suggesting that the yjbH gene might have a role in pathogenicity. Studies involving YjbH in Bacillus subtilis [15][16][17], S. aureus [18][19][20][21], and other Gram-positive bacteria [22][23][24] have reported it to be an adaptor protein responsible for proteolysis of Spx, a transcriptional regulator, via ClpXP protease [16][17][18][24][25][26]. However, the role of YjbH in the pathogenicity of S. aureus is obscure.…”

Section: Introductionmentioning

confidence: 99%

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YjbH regulates virulence genes expression and oxidative stress resistance in Staphylococcus aureus

et al. 2021

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We previously reported that disruption of the yjbI gene reduced virulence of Staphylococcus aureus. In this study, we found virulence in both silkworms and mice was restored by introducing the yjbH gene but not the yjbI gene to both yjbI and yjbH genes-disrupted mutants, suggesting that yjbH, the gene downstream to the yjbI gene in a two-gene operon-yjbIH, is responsible for this phenomenon. We further observed a decrease in various surface-associated proteins and changes in cell envelope glycostructures in the mutants. RNA-seq analysis revealed that disruption of the yjbI and the yjbH genes resulted in differential expression of a broad range of genes, notably, significant downregulation of genes involved in virulence and oxidative stress. Administration of N-acetyl-L-cysteine, a free-radical scavenger, restored the virulence in both the mutants. Our findings suggested that YjbH plays a role in staphylococcal pathogenicity by regulating virulence gene expression, affecting the bacterial surface structure, and conferring resistance to oxidative stress in a host.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

YjbH regulates virulence genes expression and oxidative stress resistance in Staphylococcus aureus

et al. 2021

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“…By targeting transcription factors for proteolysis, bacteria can modulate their gene expression profiles in response to new environmental stimuli. Several studies have demonstrated that the avirulent phenotypes associated with protease-deficient mutants are due in large part to such aberrant gene regulation [ 41 , 42 , 43 ]. Interestingly, we found that the clpA and clpS mutant strains exhibit formidable phenotypic changes including alterations to cell size, shape and especially in clpA , a possible defect in bacterial separation during replication.…”

Section: Discussionmentioning

confidence: 99%

Acinetobacter baumannii Strains Deficient in the Clp Chaperone-Protease Genes Have Reduced Virulence in a Murine Model of Pneumonia

et al. 2021

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Acinetobacter baumannii has emerged as a significant opportunistic Gram-negative pathogen and causative agent of nosocomial pneumonia especially in immunocompromised individuals in intensive care units. Recent advances to understand the contribution and function of A. baumannii virulence factors in its pathogenesis have begun to elucidate how this bacterium interacts with immune cells and its interesting mechanisms for multi-antibiotic resistance. Taking advantage of the availability of the A. baumannii AB5075 transposon mutant library, we investigated the impact of the A. baumannii Clp genes, which encode for a chaperone-protease responsible for the degradation of misfolded proteins, on bacterial virulence in a model of pneumonia using C57BL/6 mice and survival within J774.16 macrophage-like cells. Clp-protease A. baumannii mutants exhibit decreased virulence in rodents, high phagocytic cell-mediated killing and reduced biofilm formation. Capsular staining showed evidence of encapsulation in A. baumannii AB5075 and Clp-mutant strains. Surprisingly, clpA and clpS mutants displayed irregular cell morphology, which may be important in the biofilm structural deficiencies observed in these strains. Interestingly, clpA showed apical-like growth, proliferation normally observed in filamentous fungi. These findings provide new information regarding A. baumannii pathogenesis and may be important for the development of therapies intended at reducing morbidity and mortality associated with this remarkable pathogen.

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“…While the trfA mutant was susceptible to oxacillin and glycopeptide antibiotics, trfA upregulation in the yjbH mutant conferred antibiotics resistance (Jousselin et al 2013). In addition, Spx activates the MazEF toxin-antitoxin system, which promotes dormancy and antibiotic tolerance (Panasenko et al 2020). The lack of the extracellular proteases, such as aureolysin in the yjbH mutant led to hypervirulence in a systemic mouse infection model and enhanced colonization of the kidney and the spleen in a murine sepsis model (Austin et al 2019;Kolar et al 2013).…”

Section: Yjbh Adaptermentioning

confidence: 99%

Thiol-based redox switches in the major pathogen Staphylococcus aureus

Linzner

Loi

Fritsch

et al. 2020

Biological Chemistry

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Staphylococcus aureus is a major human pathogen, which encounters reactive oxygen, nitrogen, chlorine, electrophile and sulfur species (ROS, RNS, RCS, RES and RSS) by the host immune system, during cellular metabolism or antibiotics treatments. To defend against redox active species and antibiotics, S. aureus is equipped with redox sensing regulators that often use thiol switches to control the expression of specific detoxification pathways. In addition, the maintenance of the redox balance is crucial for survival of S. aureus under redox stress during infections, which is accomplished by the low molecular weight (LMW) thiol bacillithiol (BSH) and the associated bacilliredoxin (Brx)/BSH/bacillithiol disulfide reductase (YpdA)/NADPH pathway. Here, we present an overview of thiol-based redox sensors, its associated enzymatic detoxification systems and BSH-related regulatory mechanisms in S. aureus, which are important for the defense under redox stress conditions. Application of the novel Brx-roGFP2 biosensor provides new insights on the impact of these systems on the BSH redox potential. These thiol switches of S. aureus function in protection against redox active desinfectants and antimicrobials, including HOCl, the AGXX® antimicrobial surface coating, allicin from garlic and the naphthoquinone lapachol. Thus, thiol switches could be novel drug targets for the development of alternative redox-based therapies to combat multi-drug resistant S. aureus isolates.

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YjbH Solubility Controls Spx in Staphylococcus aureus: Implication for MazEF Toxin-Antitoxin System Regulation

Cited by 13 publications

References 57 publications

YjbH regulates virulence genes expression and oxidative stress resistance in Staphylococcus aureus

YjbH regulates virulence genes expression and oxidative stress resistance in Staphylococcus aureus

Acinetobacter baumannii Strains Deficient in the Clp Chaperone-Protease Genes Have Reduced Virulence in a Murine Model of Pneumonia

Thiol-based redox switches in the major pathogen Staphylococcus aureus

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