Inhibition of Exotoxin Production by Mobile Genetic Element SCCmec-Encoded psm-mec RNA Is Conserved in Staphylococcal Species

Ikuo, Mariko; Nagano, Gentaro; Saito, Yuki; Mao, Han; Sekimizu, Kazuhisa; Kaito, Chikara

doi:10.1371/journal.pone.0100260

Cited by 8 publications

(10 citation statements)

References 39 publications

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“…While we observed gene regulatory changes that were due to the psm-mec srRNA, they mostly comprised metabolic (e.g., riboflavin and purin/pyrimidine synthesis) rather than virulence genes, and were inconsistent between the two strains. Notably, the results of the previously claimed impact of the psm-mec locus on virulence would be negative [ 13 , 15 , 18 ], contrasting the positive effect we observed in the mouse sepsis model. Such a gene regulatory mechanism can thus be ruled out as underlying psm-mec -mediated development of S .…”

Section: Resultscontrasting

confidence: 99%

“…As a previous study suggested that the psm-mec srRNA leads to gene regulatory changes in S . epidermidis [ 15 ], based on the introduction of a psm-mec expressing plasmid into S . epidermidis , we also directly investigated whether the psm-mec locus has a gene regulatory impact in S .…”

Section: Resultsmentioning

confidence: 99%

“…While this effect has been claimed to generally explain lower virulence of hospital-associated as compared to community-associated MRSA strains [ 13 ], it is quite moderate and extensively strain-dependent [ 11 , 13 ]. Recently, the psm-mec locus has been introduced on a plasmid into some CNS that naturally lack psm-mec , and was reported to trigger gene regulatory changes [ 15 ]; but the roles that the PSM-mec peptide or the psm-mec srRNA naturally play in CNS including S . epidermidis are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis

Qin

Fisher

et al. 2017

PLoS Pathog

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Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS) with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally “unintended” interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches.

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Section: Resultscontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis

Qin

Fisher

et al. 2017

PLoS Pathog

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“…Berlon et al showed that decreased PSM-mec production is associated with significantly increased PSMα, β, delta-toxin in MRSA SSTI isolates compared with HAP and IE (6). Moreover, PSM-mec vector-transformed S. epidermidis and S. haemolyticus had a 30% reduction in their combined PSMα and delta-toxin output compared with their null-vector transformed counterparts, suggesting that the PSM-mec downregulation of PSM production is conserved in the Staphylococcus family (30). Given that MSSA lacks the SCCmec cassette and by extension PSM-mec, total MSSA PSM production may be higher than total MRSA PSM production, even though the relative proportions of PSMs produced may have similar profiles.…”

Section: Discussionmentioning

confidence: 99%

Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus

Joo

Sharma-Kuinkel

et al. 2016

Journal of Infection

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Background Phenol-soluble modulins (PSM) are amphipathic proteins produced by Staphylococcus aureus that promote virulence, inflammatory response, and biofilm formation. We previously showed that MRSA isolates from soft tissue infection (SSTI) produced significantly higher levels of PSM than MRSA isolates from hospital-acquired pneumonia (HAP) or infective endocarditis (IE). In this investigation, we sought to validate this finding in methicillin-susceptible S. aureus (MSSA) isolates. Methods MSSA isolates (n=162) from patients with SSTI, HAP, and IE were matched 1:1:1 based on geographic origin of the infection to form 54 triplets (North America n=27, Europe n=25, Australia n=2). All isolates underwent spa-typing and were classified using eGenomics. In vitro PSM production was quantified by high performance liquid chromatography/mass spectrometry. Fischer’s Exact Test and the Kruskal-Wallis test were used for statistical analysis. Results Spa1 was more common in SSTI (14.81% SSTI, 3.70% HAP, 1.85% IE) (p<0.03). Spa2 was more common in HAP (0% SSTI, 12.96% HAP, 3.70% IE) (p<0.01). Levels of PSMα1-4 all differed significantly among the three clinical groups, with SSTI isolates producing the highest levels and IE producing the lowest levels of PSMα1-4. Spa1 isolates produced significantly more delta-toxin (p<0.03) than non-Spa1 isolates. No associations between PSM levels and clinical outcome of SSTI, HAP, or IE were identified. Conclusion Production of PSMα1-4 is highest in SSTI MSSA isolates, supporting the hypothesis that these peptides are important for SSTI pathogenesis. These findings are similar to those described in MRSA, and demonstrate that associations between PSM levels and type of infection are independent of the methicillin resistance status of the isolate.

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“…The dissemination success of the ST764 clone might be related to the psm‐mec mutation, but this requires further investigation. The psm‐mec is present not only in MRSA, but also in methicillin‐resistant coagulase‐negative Staphylococci, including Staphylococcus epidermidis and Staphylococcus haemolyticus . Additional studies are needed to investigate the relation of psm‐mec mutations to the bacterial phenotype or specific clinical features of MRSA diseases as well as methicillin‐resistant coagulase‐negative Staphylococci diseases.…”

Section: The Psm‐mec Mutations and Their Correspondence To Sccmec Typmentioning

confidence: 99%

Epidemiological study on the relationship between toxin production and psm‐mec mutations in MRSA isolates in Thailand

Tabuchi

Lulitanond

et al. 2020

Microbiology and Immunology

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In this present study, we investigated the phenol‐soluble modulin (psm‐mec) mutations, the staphylococcal cassette chromosome mec (SCCmec) types, and toxin production in 102 methicillin‐resistant Staphylococcus aureus (MRSA) isolates from the northeast and central regions of Thailand. The MRSA isolates carrying ‐7T>C psm‐mec in Type II SCCmec (n = 18) and the MRSA isolates carrying no psm‐mec in Type IV (n = 8) or Type IX SCCmec (n = 4) had higher hemolytic activity against sheep erythrocytes than MRSA isolates carrying intact psm‐mec in Type III SCCmec (n = 34), but MRSA isolates carrying no psm‐mec in Type I SCCmec (n = 27) did not.

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Inhibition of Exotoxin Production by Mobile Genetic Element SCCmec-Encoded psm-mec RNA Is Conserved in Staphylococcal Species

Cited by 8 publications

References 39 publications

Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis

Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis

Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus

Epidemiological study on the relationship between toxin production and psm‐mec mutations in MRSA isolates in Thailand

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