Key Role of α-Toxin in Fatal Pneumonia Caused by <i>Staphylococcus aureus</i> Sequence Type 398

Bonesso, Mariana Fávero; Yeh, Anthony J.; Villaruz, Amer E.; Joo, Hwang-Soo; McCausland, Joshua W.; Fortaleza, Carlos Magno Castelo Branco; Cavalcante, R. S.; Sobrinho, Moises T.; Ronchi, Carlos Fernando; Cheung, Gordon Y. C.; Cunha, Matheus Luís Oliveira; Otto, Michael

doi:10.1164/rccm.201506-1225le

Cited by 22 publications

(19 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the ST398 lineage has only sporadically and to a minor extent been known to cause such infections, our present study reveals that it has grown to a considerable problem in China, representing the source for about one third of CA-SA infections in Shanghai. Notably, our data also indicate that the ST398 cases are not related to contact with livestock, which is in accordance with data from New York and Brazil 11 12 .…”

Section: Discussionsupporting

confidence: 92%

“…Increased expression of Agr-controlled toxins, in particular α-toxin, has recently been made responsible for the high virulence of ST398 isolates that caused fatal pneumonia 12 . In our previous study 19 , we showed that Agr (as measured by expression of RNAIII), α-toxin, and phenol-soluble modulins (PSMs) α also showed increased expression in our isolates.…”

Section: Resultsmentioning

confidence: 99%

“…Whole genome sequencing of human CA-SA ST398 revealed that it represents a human-adapted lineage that is different in genetic composition from animal-associated ST398 clones 11 . The molecular processes underlying the capacity of CA-SA ST398 to infect healthy individuals and spread sustainably in the population are poorly understood, but recent results obtained with ST398 isolates from Brazil that caused fatal pneumonia indicate an important role of Agr-controlled toxins, in particular α-toxin, in ST398 virulence 12 .…”

mentioning

confidence: 99%

See 2 more Smart Citations

Role of the ESAT-6 secretion system in virulence of the emerging community-associated Staphylococcus aureus lineage ST398

Wang

Liu

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

Novel Staphylococcus aureus clones continue to emerge that cause infections in otherwise healthy people. One example is the sequence type (ST) 398 lineage, which we show here is increasing in importance as a significant cause of community-associated (CA) human infections in China. We have a profound lack of understanding about what determines the considerable virulence potential of such newly emerging clones. Information about the contribution to virulence of the more recently discovered ESAT-6 secretion system (ESS) has remained particularly scarce. The Chinese ST398 isolates exhibited significantly increased expression of ESS genes as compared to predominant hospital-associated clones, which we found is likely due to increased expression of the accessory gene regulator (Agr) system and control of ESS by Agr. Importantly, deletion of essB in ST398 resulted in significantly reduced resistance to neutrophil killing and decreased virulence in murine skin and blood infection models. Our results demonstrate a key function of ESS in promoting virulence and mechanisms of resistance to innate host defense in an important emerging CA-S. aureus lineage. They suggest that ESS has a so far underestimated role in promoting aggressive virulence and epidemiological success of S. aureus.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Role of the ESAT-6 secretion system in virulence of the emerging community-associated Staphylococcus aureus lineage ST398

Wang

Liu

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Occasionally, LA-MRSA ST398 is directly or indirectly transferred from livestock to humans [ 8 ], where it normally causes moderate and only occasionally severe infection [ 9 – 11 ]. In contrast, human-adapted ST398 isolates often cause severe and fatal infections and are genetically different from LA clones [ 7 , 12 , 13 ]. Some of the distinct genetic features of those isolates are reportedly important for the adaptation to humans as hosts, which may explain the more pronounced severity of infection they can cause in humans [ 12 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution

Zheng

Wang

et al. 2018

Genome Med

Self Cite

View full text Add to dashboard Cite

BackgroundSevere infections with highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are a global problem. However, the molecular events defining the evolution of CA-MRSA are still poorly understood. MRSA of sequence type (ST) 398 is known to frequently infect livestock, while ST398 isolates infecting humans are commonly methicillin-susceptible or represent MRSA originating from livestock-associated (LA)-MRSA.MethodsWe used whole genome sequencing of newly detected CA-MRSA ST398 isolates, in comparison to geographically matched LA-MRSA and methicillin-sensitive ST398, to determine their evolutionary history. Furthermore, we used phenotypic analyses including animal infection models to gain insight into the evolution of virulence in these CA-MRSA isolates. Finally, we determined methicillin resistance and expression of the methicillin resistance-conferring gene mecA and its penicillin-binding protein product, PBP2a, in a large series of CA-MRSA strains of divergent STs.ResultsWe report several cases of severe and fatal infections due to ST398 CA-MRSA. The responsible isolates showed the typical genetic characteristics reported for human-adapted methicillin-sensitive ST398. Whole genome sequencing demonstrated that they evolved from human-adapted, methicillin-susceptible clones on several different occasions. Importantly, the isolates had not undergone consistent genetic alterations or changes in virulence as compared to their methicillin-susceptible predecessors. Finally, we observed dramatically and consistently lower methicillin resistance and expression of the resistance gene mecA, as compared to hospital-associated MRSA strains, in a diverse selection of CA-MRSA strains.ConclusionsOur study presents evidence for the development of highly virulent human-adapted ST398 CA-MRSA isolates from methicillin-susceptible predecessors. Notably, our investigation indicates that, in contrast to widespread notions, the development of CA-MRSA is not necessarily associated with the acquisition of specific virulence genes or other virulence-increasing changes. Rather, our findings emphasize the importance of the CA-MRSA-characteristic staphylococcal cassette chromosome mec types, which provide only low-level methicillin resistance, for that process. Our findings are of particular importance for the diagnosis of CA-MRSA, inasmuch as they indicate that the presence of specific virulence genes cannot generally be used for that purpose.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-018-0514-9) contains supplementary material, which is available to authorized users.

show abstract

“…Since then, ST398 has spread rapidly to other animals and has been increasingly related to infections not only in rural workers but also in people and animals without risk factors [13,47]. Although susceptible to oxacillin, this S. aureus lineage is associated with severe infections, as reported by Bonesso et al [48] in patients with ventilator-associated pneumonia in whom the infection was fatal in most cases.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Risk Factors for Nasal and Oropharyngeal Carriage of Staphylococcus Aureus in Insulin-Dependent Diabetics Individuals

Teixeira

Fortaleza

Souza

et al. 2020

Preprint

View full text Add to dashboard Cite

Individuals with insulin-dependent diabetes are a risk group for infections caused by Staphylococcus aureus. The objective of this study was to determine the prevalence and risk factors for nasal and oropharyngeal carriage of S. aureus and MRSA in insulin-dependent diabetic individuals from Botucatu, São Paulo, Brazil. Additionally, susceptibility profiling, detection of the mecA gene, SCCmec typing and molecular typing by PFGE and MLST were performed in nasal and oropharyngeal swabs of 312 subjects. The prevalence of S. aureus and MRSA was 30.4% and 4.8%, respectively. SCCmec type IV was the predominant type among isolates, although some carried SCCmec types I and II. MRSA and MSSA clones were detected among the isolates of this population. In addition, an important clonal lineage (ST398) was identified among resistant and susceptible isolates. Age and lung disease were negatively associated with S. aureus carriage, while lower-extremity ulcers were a risk factor for S. aureus carriage. For MRSA, only male gender was a risk factor. These data suggest widespread dissemination of MRSA in the insulin-dependent diabetic population studied, as well as the emergence of important lineages among these individuals.

show abstract

Key Role of α-Toxin in Fatal Pneumonia Caused by Staphylococcus aureus Sequence Type 398

Cited by 22 publications

References 9 publications

Role of the ESAT-6 secretion system in virulence of the emerging community-associated Staphylococcus aureus lineage ST398

Role of the ESAT-6 secretion system in virulence of the emerging community-associated Staphylococcus aureus lineage ST398

Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution

Prevalence and Risk Factors for Nasal and Oropharyngeal Carriage of Staphylococcus Aureus in Insulin-Dependent Diabetics Individuals

Contact Info

Product

Resources

About