Contribution of YjbIH to Virulence Factor Expression and Host Colonization in
            <i>Staphylococcus aureus</i>

Austin, Crystal M.; Garabaglu, Siamak; Krute, Christina N.; Ridder, Miranda J.; Seawell, Nichole A.; Markiewicz, Mary A.; Boyd, Jeffrey M.; Bose, Jeffrey L.

doi:10.1128/iai.00155-19

Cited by 21 publications

(30 citation statements)

References 109 publications

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“…The identified genes have not been previously identified to have roles in aggravating virulence. However, in contrast to our result, a recent study(37) showed that retro-orbital injection of 0904::Tn resulted in increased colonization in the C57BL/6J mouse kidney. The differences might have been observed owing to the differences in the infection models and the genetic backgrounds of the mice used.…”

Section: Discussioncontrasting

confidence: 99%

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Uncovering Staphylococcus aureus genes with roles in pathogenicity by silkworm infection model

Paudel

Hamamoto

Panthee

et al. 2019

Preprint

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22The regulatory network of virulence factors production by Staphylococcus aureus, an 23 opportunistic pathogen, is incompletely understood, and the functions of many 24 uncharacterized genes in its genome remain to be uncovered. We screened 380 25 function unassigned genes disrupted mutants of the community-acquired methicillin-26 resistant S. aureus USA300 for pathogenicity using silkworms and identified 11 27 strains with reduced silkworm killing ability. Nine out of the 11 strains displayed 28 reduced virulence in the mouse model as evidenced by reduced colony-forming units 29 in organs of the infected mice. Three of the identified gene-disrupted mutants had 30 reduced hemolytic activity, one among the three also had reduced proteolytic activity 31 and pigment production. These results suggest that silkworm model could identify 32 the genes required for virulence in the mouse model. The newly identified genes 33 involved in virulence in this study facilitates the further understanding of the 34 pathogenicity of S. aureus. 35 36 Importance 37We performed a large scale screening of mutants of Staphylococcus aureus with 38 disruption in function unassigned genes using silkworm infection model and 39identified eleven genes required for full virulence in silkworm. Nine of the eleven 40 genes were involved in virulence in mice and were previously not known to 41 aggravate virulence of S. aureus. The results suggest that silkworm model is suitable 42 for quantitative measurement of virulence, which is shared between silkworms and 43 mammals. 44 45 48 endocarditis, and bacteremia(1). With an increasing rise in the resistance of 49 methicillin-resistant S. aureus (MRSA), the appearance of vancomycin-intermediate 50 S. aureus (VISA)(2, 3), and vancomycin-resistant S. aureus (VRSA)(4-7), S. aureus 51 has become one of the leading causes of morbidity and mortality and has been 52 categorized as a threat among antimicrobial-resistant strains by the World Health 53 Organization(8) and the Centers for Disease Control and Prevention(9). The ability of 54 S. aureus to rapidly infect host is due to the expression and release of many 55 virulence factors such as cytolysins, hemolysins, leukocidins, coagulases, adhesins, 56 proteases, nucleases, enterotoxins, lipases, exfoliative toxins, and immune-57 modulatory factors, and cell surface-associated proteins including Protein A and 58fibrinogen-, fibronectin-and collagen-binding proteins(10-15). Although some of the 59 pathways of virulence factor expression and regulation such as sarA, agr, srrAB, 60 saeRS, ArlRS,(16) in S. aureus as well as the factors acting via one or more of these 61 pathways (17)(18)(19) are studied, the understanding of the production and regulation of 62 virulence factors in S. aureus is through a multifaceted network that is still obscure 63 and many genes with unknown functions in S. aureus genome with roles in virulence 64 and pathogenicity remain to be uncovered. 65 66Since virulence is the degree of pathogenicity of a microorganism that is mostly...

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Section: Discussioncontrasting

confidence: 99%

“…Besides, the 0904::Tn strain had a reduced pigment production capacity on the sheep blood agar plate (Figure 3). The reduced pigment and protease production of 0904::Tn were in accordance to previous reports(35, 37).…”

Section: Resultssupporting

confidence: 93%

Uncovering Staphylococcus aureus genes with roles in pathogenicity by silkworm infection model

Paudel

Hamamoto

Panthee

et al. 2019

Preprint

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“…B), with the smaller of the two showing greater intensity and peaking at stationary phase (OD 650 = 1.7). The proximity of the hbo gene, also called yjbI (Austin et al , ) and located just 44 bp upstream of yjbH , coupled with a strong rho‐ independent terminator ( ∆G = −16 kcal mol –1 ) (de Hoon et al , ) downstream of yjbH (Fig. A), implicates the 1.2 kb transcript to encompass hbo ‐ yjbH.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, a recent paper by Austin et al also reported the contribution of YjbH to pigmentation and host colonization in S. aureus (Austin et al , ). While some of our findings are complementary (e.g.…”

Section: Discussionmentioning

confidence: 99%

CspA regulation of Staphylococcus aureus carotenoid levels and σ^B activity is controlled by YjbH and Spx

Donegan

Manna

Tseng

et al. 2019

Molecular Microbiology

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Staphyloxanthin, a carotenoid in S. aureus, is a powerful antioxidant against oxidative stresses. The crtOPQMN operon driving pigment synthesis is under the control of σ B . CspA, a cold shock protein, is known to control σ B activity. To ascertain genes that regulate cspA, we screened a transposon library that exhibited reduced cspA expression and pigmentation. We found that the adaptor protein YjbH activates cspA expression. Spx, the redox-sensitive transcriptional regulator and a proteolytic target for YjbH and ClpXP, complexes with αCTD of RNAP prior to binding the cspA promoter to repress cspA activity. Increased cspA expression in trans in the inactive spx C10A mutant of JE2 did not enhance pigment production while it did in JE2, suggesting that cspA is downstream to Spx in pigmentation control. As the staphyloxanthin pigment is critical to S. aureus survival in human hosts, we demonstrated that the cspA and yjbH mutants survived less well than the parent in whole blood killing assay. Collectively, our studies suggest a pathway wherein YjbH and ClpXP proteolytically cleave Spx, a repressor of cspA transcription, to affect σ B -dependent carotenoid expression, thus providing a critical link between intracellular redox sensing by Spx and carotenoid production to improve S. aureus survival during infections.

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“…If intermolecular disulfide bonds involving the CxxC motif were essential for YjbH Lm to interact with any of the cysteine-containing proteins, we would expect the interacting proteins to bind wild type YjbH Lm protein but not the YjbH C27/30A mutant. The observation that YjbH C27/30A could still bind two proteins suggested that YjbH Lm can interact with proteins at a site other than It is interesting to note that the L. monocytogenes ∆yjbH mutant was more resistant to nitrosative stress while the B. subtilis and S. aureus ∆yjbH mutants are more sensitive (12,35). However, expressing the YjbH Bs protein in ∆yjbH Lm fully restored its sensitivity to SNP.…”

Section: Downloaded Frommentioning

confidence: 99%

YjbH Requires Its Thioredoxin Active Motif for the Nitrosative Stress Response, Cell-to-Cell Spread, and Protein-Protein Interactions in Listeria monocytogenes

Ruhland

2020

J Bacteriol

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Listeria monocytogenes is a model facultative intracellular pathogen. Tight regulation of virulence proteins is essential for a successful infection, and the gene encoding the annotated thioredoxin YjbH was identified in two forward genetic screens as required for virulence factor production. Accordingly, an L. monocytogenes strain lacking yjbH is attenuated in a murine model of infection. However, the function of YjbH in L. monocytogenes has not been investigated. Here, we provide evidence that L. monocytogenes YjbH is involved in the nitrosative stress response, likely through its interaction with the redox-responsive transcriptional regulator SpxA1. YjbH physically interacted with SpxA1, and our data support a model in which YjbH is a protease adaptor that regulates SpxA1 protein abundance. Whole-cell proteomics identified eight additional proteins whose abundance was altered by YjbH, and we demonstrated that YjbH physically interacted with each in bacterial two-hybrid assays. Thioredoxin proteins canonically require active motif cysteines for function, but thioredoxin activity has not been tested for L. monocytogenes YjbH. We demonstrated that cysteine residues of the YjbH thioredoxin domain active motif are essential for L. monocytogenes sensitivity to nitrosative stress, cell-to-cell spread in a tissue culture model of infection, and several protein-protein interactions. Together, these results demonstrated that the function of YjbH in L. monocytogenes requires its thioredoxin active motif and that YjbH has a role in the posttranslational regulation of several proteins, including SpxA1. IMPORTANCE The annotated thioredoxin YjbH in Listeria monocytogenes has been implicated in virulence, but its function in the cell is unknown. In other bacterial species, YjbH is a protease adaptor that mediates degradation of the transcriptional regulator Spx. Here, we investigated the function of L. monocytogenes YjbH and demonstrated its role in the nitrosative stress response and posttranslational regulation of several proteins with which YjbH physically interacts, including SpxA1. Furthermore, we demonstrated that the cysteine residues of the YjbH thioredoxin active motif are required for the nitrosative stress response, cell-to-cell spread, and some protein-protein interactions. YjbH is widely conserved among Firmicutes, and this work reveals its unique requirement of the thioredoxin-active motif in L. monocytogenes.

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Contribution of YjbIH to Virulence Factor Expression and Host Colonization in Staphylococcus aureus

Cited by 21 publications

References 109 publications

Uncovering Staphylococcus aureus genes with roles in pathogenicity by silkworm infection model

Uncovering Staphylococcus aureus genes with roles in pathogenicity by silkworm infection model

CspA regulation of Staphylococcus aureus carotenoid levels and σ^B activity is controlled by YjbH and Spx

YjbH Requires Its Thioredoxin Active Motif for the Nitrosative Stress Response, Cell-to-Cell Spread, and Protein-Protein Interactions in Listeria monocytogenes

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Contribution of YjbIH to Virulence Factor Expression and Host Colonization in Staphylococcus aureus

Cited by 21 publications

References 109 publications

Uncovering Staphylococcus aureus genes with roles in pathogenicity by silkworm infection model

Uncovering Staphylococcus aureus genes with roles in pathogenicity by silkworm infection model

CspA regulation of Staphylococcus aureus carotenoid levels and σB activity is controlled by YjbH and Spx

YjbH Requires Its Thioredoxin Active Motif for the Nitrosative Stress Response, Cell-to-Cell Spread, and Protein-Protein Interactions in Listeria monocytogenes

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CspA regulation of Staphylococcus aureus carotenoid levels and σ^B activity is controlled by YjbH and Spx