Mutation of the Streptococcus gordonii Thiol-Disulfide Oxidoreductase SdbA Leads to Enhanced Biofilm Formation Mediated by the CiaRH Two-Component Signaling System

Davey, Lauren; Halperin, Scott A.; Lee, Song F.

doi:10.1371/journal.pone.0166656

Cited by 11 publications

(11 citation statements)

References 60 publications

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“…It is interesting to note that the msrAB mutant was defective in biofilm formation and outcompeted by the parent in a mouse oral colonization assay. In a previous study, the disulfide bond oxidase sdbA mutant of S. gordonii formed more biofilm in vitro and also outcompeted the parent in vivo [16]. In the case of the msrA mutant, the in vitro biofilm formation ability was not altered, but it was outcompeted by the parent in oral colonization.…”

Section: Discussionmentioning

confidence: 77%

“…In addition, it has been shown that in vitro biofilm formation correlates to in vivo colonization in mice for S. gordonii [16] and S. pneumoniae [17]. Given the findings in biofilm formation, we performed a competitive assay between the parent and msrAB mutant in a mouse model of oral colonization [16,18]. We also included the msrA mutant for comparison.…”

Section: Msrab Is An Extracytoplasmic Enzyme and Required For Biofilmmentioning

confidence: 99%

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The MsrAB reducing pathway of Streptococcus gordonii is needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice

Jalal

Lee

2020

PLoS ONE

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The ability of Streptococcus gordonii to cope with oxidative stress is important for survival and persistence in dental plaque. In this study, we used mutational, phenotypic, and biochemical approaches to characterize the role of a methionine sulfoxide reductase (MsrAB) and proteins encoded by genes in the msrAB operon and an adjacent operon in oxidative stress tolerance in S. gordonii. The results showed that MsrAB and four other proteins encoded in the operons are needed for protection from H 2 O 2 and methionine sulfoxide. These five proteins formed a reducing pathway that was needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice. In the pathway, MsrAB was the enzyme that repaired oxidatively damaged proteins, and the two thioredoxin-like lipoproteins (SdbB and Sgo_1177) and two CcdA proteins were proteins that maintained the catalytic cycle of MsrAB. Consistent with the role in oxidative stress tolerance, the production of MsrAB, SdbB, and Sgo_11777 was induced in aerobic growth and planktonic cells.

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Section: Discussionmentioning

confidence: 77%

Section: Msrab Is An Extracytoplasmic Enzyme and Required For Biofilmmentioning

confidence: 99%

The MsrAB reducing pathway of Streptococcus gordonii is needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice

Jalal

Lee

2020

PLoS ONE

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“…The GBS response regulator CiaR has been shown to modulate GBS virulence and interaction with host cells (Quach et al, 2009; Mu et al, 2016). Importance for CiaRH in virulence has also been well-described in pneumococcus and oral streptococci (Qi et al, 2004; Blanchette-Cain et al, 2013; Trihn et al, 2013; Davey et al, 2016; Hentrich et al, 2016; Zhu et al, 2017). CiaRH expression is down-regulated in GBSΔ cas9 mutants (Figure 5I, Supplementary Figure S2, and Supplementary Table S2); therefore, we hypothesized that CiaR-regulated genes would also be modulated in the Δ cas9 mutant compared to WT COH1.…”

Section: Discussionmentioning

confidence: 85%

Cas9 Contributes to Group B Streptococcal Colonization and Disease

et al. 2019

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Group B Streptococcus (GBS) is a major opportunistic pathogen in certain adult populations, including pregnant women, and remains a leading etiologic agent of newborn disease. During pregnancy, GBS asymptomatically colonizes the vaginal tract of 20–30% of healthy women, but can be transmitted to the neonate in utero or during birth resulting in neonatal pneumonia, sepsis, meningitis, and subsequently 10–15% mortality regardless of antibiotic treatment. While various GBS virulence factors have been implicated in vaginal colonization and invasive disease, the regulation of many of these factors remains unclear. Recently, CRISPR-associated protein-9 (Cas9), an endonuclease known for its role in CRISPR/Cas immunity, has also been observed to modulate virulence in a number of bacterial pathogens. However, the role of Cas9 in GBS colonization and disease pathogenesis has not been well-studied. We performed allelic replacement of cas9 in GBS human clinical isolates of the hypervirulent sequence-type 17 strain lineage to generate isogenic Δ cas9 mutants. Compared to parental strains, Δ cas9 mutants were attenuated in murine models of hematogenous meningitis and vaginal colonization and exhibited significantly decreased invasion of human brain endothelium and adherence to vaginal epithelium. To determine if Cas9 alters transcription in GBS, we performed RNA-Seq analysis and found that 353 genes (>17% of the GBS genome) were differentially expressed between the parental WT and Δ cas9 mutant strain. Significantly dysregulated genes included those encoding predicted virulence factors, metabolic factors, two-component systems (TCS), and factors important for cell wall formation. These findings were confirmed by qRT-PCR and suggest that Cas9 may regulate a significant portion of the GBS genome. We studied one of the TCS regulators, CiaR, that was significantly downregulated in the Δ cas9 mutant strain. RNA-Seq analysis of the WT and Δ ciaR strains demonstrated that almost all CiaR-regulated genes were also significantly regulated by Cas9, suggesting that Cas9 may modulate GBS gene expression through other regulators. Further we show that CiaR contributes to GBS vaginal colonization and persistence. Altogether, these data highlight the potential complexity and importance of the non-canonical function of Cas9 in GBS colonization and disease.

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“… 29 , 30 Moreover, other resistance determinants such as MurMN and CiaRH affecting peptidoglycan structure are known to influence β-lactam resistance. 31 , 32 Among the indels observed in the resistant isolates in this study, sulA is characterized by a 6-bp insertion, resulting in the insertion of two amino acids (Arg and Pro) in dihydropteroate synthase, thereby conferring resistance to SXT. 33 Concurrently, other studies have reported nonsynonymous SNPs in the dihydrofolate reductase encoding dfr gene in SXT isolates.…”

Section: Discussionmentioning

confidence: 88%

Comparative genomic analysis of multidrug-resistant <em>Streptococcus pneumoniae</em> isolates

Pan

Zhang

Dong

et al. 2018

IDR

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IntroductionMultidrug resistance in Streptococcus pneumoniae has emerged as a serious problem to public health. A further understanding of the genetic diversity in antibiotic-resistant S. pneumoniae isolates is needed.MethodsWe conducted whole-genome resequencing for 25 pneumococcal strains isolated from children with different antimicrobial resistance profiles. Comparative analysis focus on detection of single-nucleotide polymorphisms (SNPs) and insertions and deletions (indels) was conducted. Moreover, phylogenetic analysis was applied to investigate the genetic relationship among these strains.ResultsThe genome size of the isolates was ~2.1 Mbp, covering >90% of the total estimated size of the reference genome. The overall G+C% content was ~39.5%, and there were 2,200–2,400 open reading frames. All isolates with different drug resistance profiles harbored many indels (range 131–171) and SNPs (range 16,103–28,128). Genetic diversity analysis showed that the variation of different genes were associated with specific antibiotic resistance. Known antibiotic resistance genes (pbps, murMN, ciaH, rplD, sulA, and dpr) were identified, and new genes (regR, argH, trkH, and PTS-EII) closely related with antibiotic resistance were found, although these genes were primarily annotated with functions in virulence as well as carbohydrate and amino acid transport and metabolism. Phylogenetic analysis unambiguously indicated that isolates with different antibiotic resistance profiles harbored similar genetic backgrounds. One isolate, 14-LC.ER1025, showed a much weaker phylogenetic relationship with the other isolates, possibly caused by genomic variation.ConclusionIn this study, although pneumococcal isolates had similar genetic backgrounds, strains were diverse at the genomic level. These strains exhibited distinct variations in their indel and SNP compositions associated with drug resistance.

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Mutation of the Streptococcus gordonii Thiol-Disulfide Oxidoreductase SdbA Leads to Enhanced Biofilm Formation Mediated by the CiaRH Two-Component Signaling System

Cited by 11 publications

References 60 publications

The MsrAB reducing pathway of Streptococcus gordonii is needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice

The MsrAB reducing pathway of Streptococcus gordonii is needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice

Cas9 Contributes to Group B Streptococcal Colonization and Disease

Comparative genomic analysis of multidrug-resistant <em>Streptococcus pneumoniae</em> isolates

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