Clonal differences in Staphylococcus aureus bacteraemia-associated mortality

Recker, Mario; Laabei, Maisem; Toleman, Michelle S.; Reuter, Sandra; Saunderson, Rebecca B.; Blane, Beth; Ouadi, Khadija; Stevens, Emily; Yokoyama, Maho; Steventon, Joseph; Thompson, Luke; Milne, Gregory; Bayliss, Sion C.; Bacon, Leann; Peacock, Sharon J.; Massey, Ruth C.

doi:10.1038/s41564-017-0001-x

Cited by 115 publications

(133 citation statements)

References 33 publications

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“…However, despite significant investment and multiple diverse S. aureus components including toxins, surface expressed proteins and capsule being targeted, vaccines have provided no significant level protection when used in human trials 31 . Recent studies on populations of clinical isolates may provide an answer to some of these failures, where significant variability in the expression of toxins and capsule has been demonstrated 12-14,32 . The isolates not expressing the target would therefore evade the immune response elicited by the vaccine, affecting its coverage and effectivity.…”

Section: Discussionmentioning

confidence: 99%

“…With many genes described only as encoding hypothetical proteins, or ascribed a putative function based on amino acid homology to other characterised proteins, it is clear we have much to learn about this microbial pathogen. In recent work we have developed a functional genomics approach to begin to bring genome sequence data and the study of S. aureus pathogenicity together 12-14,28 . In doing so we have identified several novel effectors of the ability of S. aureus isolates to secrete cytolytic toxins, one of which is MasA, a putative membrane bound protein.…”

Section: Discussionmentioning

confidence: 99%

“…Without this the bacteria are less able to defend themselves from immune attack. Not only is there huge diversity and complexity to the means by which S. aureus interacts with its host to cause disease, recent work suggests that clones might utilise distinct pathways to achieve this 12 . With such complexity and functional redundancy, this may explain why efforts to develop interventions, such as a protective vaccine, have not yet been successful.…”

Section: Introductionmentioning

confidence: 99%

“…To better understand the pathogenicity of S. aureus , we developed a functional genomics approach to make use of the many thousands of clinical S. aureus isolates that have been sequenced 12-14 . This has enabled us to identify novel loci that affect the ability of S. aureus to both secrete cytolytic toxins and form biofilm 12-14 . One locus we found to be associated with the ability of the bacteria to secrete toxins was annotated as a putative membrane bound protein.…”

Section: Introductionmentioning

confidence: 99%

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A small membrane protein critical to both the offensive and defensive capabilities of Staphylococcus aureus

Duggan

Laabei

Al-Nahari

et al. 2019

Preprint

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Staphylococcus aureus is a major human pathogen, where the widespread emergence of antibiotic resistance is making infections more challenging to treat. Toxin induced tissue damage and resistance to the host’s immune system are well established as critical to its ability to cause disease. However, recent attempts to study S. aureus pathogenicity at a population level have revealed significant complexity and hierarchical levels of regulation. In an effort to better understand this we have identified and characterized a principle effector protein, MasA. The inactivation of this small highly-conserved membrane protein simultaneously disrupts toxin production and impairs S. aureus’ ability to resist several aspects of the innate immune system. These pleiotropic effects are mediated by both a change in the stability of the bacterial membrane and the dysregulation of iron homeostasis, which results in a significant impairment in the ability of S. aureus to cause infection in both a subcutaneous and a sepsis model of infection. That proteins with such major effects on pathogenicity remain unidentified in a bacterium as well studied as S. aureus demonstrates how incomplete our understanding of their ability to cause disease is, an issue that needs to be addressed if effective control and treatment strategies are to be developed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A small membrane protein critical to both the offensive and defensive capabilities of Staphylococcus aureus

Duggan

Laabei

Al-Nahari

et al. 2019

Preprint

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“…S. aureus is a dangerous and versatile human pathogen because of its ability to cause various types of infections, including skin and soft tissue sepsis, pneumonia, bloodstream infections (BSIs), osteomyelitis and infective endocarditis (IE) [1]. Higher mortality rate (15–25%) was recently reported from serious S. aureus infections, particularly bacteremia and endocarditis [2,3]. IE is a major devastating complications of Staphylococcal bacteremia [3,4].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Staphylococcal Superantigens and their association among bacteremic and Infective Endocarditis patients in Egypt

Elsherif

Helal

El-Ansary

et al. 2020

Preprint

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31Aim: Infective endocarditis (IE) is a major complication of Staphylococcus (S.) aureus infection 32 in humans particularly those with bacteremia. Although Staphylococcus species are commensal 33 on or in different parts of the human body, it is also known to be a serious pathogen causing 34 bacteremia and sepsis that could lead to IE. Therefore, our aim was to assess the prevalence as 35 well as phenotypic and genotypic association of the Staphylococcal superantigens (SAgs) among 36 bacteremic and IE patients.37 Methods: This study was conducted on Staphylococcus isolates recovered from bacteremic and 38 IE patients. The isolates were screened phenotypically for the detection of SAgs including 39Staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin-1 (TSST-1). Molecular 40 detection and analysis of sea, seb, sec, sed, see and tsst-1, the major SAgs coding genes were 41 performed using PCR and agarose gel electrophoresis, respectively. The obtained findings were 42 statistically analyzed using standard methods. 43Results: Detection of SAgs using ELISA revealed that 12 (46%) isolates were positive for 44 enterotoxin production. However, the PCR revealed that 19 (73%) isolates were positive for 45 enterotoxin genes with the highest prevalence of the sea gene (79%), followed by the seb (63%), 46 tsst-1 (21%). The least frequent gene was the sed (5.3%). Accordingly, phenotypic and genotypic 47 screening for prevalence of SAgs among Staphylococcal isolates showed significant difference 48 (P value =0.046703), however, no significant correlation could be observed among the coagulase 49 negative Staphylococci (CoNS) isolates (P value =0.248213). Statistical correlations between 50 bacteremic and IE isolates with respect to prevalence of SAgs, showed no significant difference 51 (P-value = 0.139, Effect size = 0.572) indicating no specific association between any of the 52 detected SAgs and IE. 3 53 Conclusion: no significant difference has been found between Staphylococcal IE and bacteremia 54 isolates regarding both phenotypic and genotypic detection of the most commonly SAgs. 55 Therefore, all Staphylococcal bacteremic patients are suspected for IE. Also, future work should 56 be conducted for analysis of SAgs gene expression. 57 58 59 Introduction 60 S. aureus is a dangerous and versatile human pathogen because of its ability to cause various 61 types of infections, including skin and soft tissue sepsis, pneumonia, bloodstream infections 62 (BSIs), osteomyelitis and infective endocarditis (IE) [1]. Higher mortality rate (15-25%) was 63 recently reported from serious S. aureus infections, particularly bacteremia and endocarditis 64 [2,3]. IE is a major devastating complications of Staphylococcal bacteremia [3,4]. In 2018, 65 Asgeirsson et al. reported that S. aureus is the foremost cause of IE where it comprises about 15-66 40% of all IE cases worldwide [3]. 67 IE is caused principally with bacteria or fungi where serious clinically relevant complications 68 including, damaging of one or more of the ...

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Staphylococcus aureusST228 and ST239 as models for expression studies of diverse markers during osteoblast infection and persistence

et al. 2021

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Clonal differences in Staphylococcus aureus bacteraemia-associated mortality

Cited by 115 publications

References 33 publications

A small membrane protein critical to both the offensive and defensive capabilities of Staphylococcus aureus

A small membrane protein critical to both the offensive and defensive capabilities of Staphylococcus aureus

Prevalence of Staphylococcal Superantigens and their association among bacteremic and Infective Endocarditis patients in Egypt

Staphylococcus aureusST228 and ST239 as models for expression studies of diverse markers during osteoblast infection and persistence

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