Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases

Rooijakkers, Suzan H.M.; Ruyken, Maartje; Roos, Anja; Daha, Mohamed R.; Presanis, Julia S.; Sim, Robert B.; Wamel, Willem J. B. van; Kessel, Kok P. M. van; Strijp, Jos A. G. van

doi:10.1038/ni1235

Cited by 373 publications

(364 citation statements)

References 42 publications

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“…The functions of these exported proteins are unknown, but we speculate that at least some may be virulence factors because proteins exported from bacteria are often toxins or proteins that interfere with the immune system (Beuscher et al, 1995;Emody et al, 2003;Jongerius et al, 2007;Rooijakkers et al, 2005). Several genes involved in transfer of the plasmid were identified, supporting previous in vivo and in vitro observations of horizontal pQC transfer .…”

Section: Discussionsupporting

confidence: 80%

Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain

Paauw

Caspers²,

Hall

et al. 2009

Microbiology

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Bacterial strains differ in their ability to cause hospital outbreaks. Using comparative genomic hybridization, Enterobacter cloacae complex isolates were studied to identify genetic markers specific for Enterobacter cloacae complex outbreak strains. No outbreak-specific genes were found that were common in all investigated outbreak strains. Therefore, the aim of our study was to identify specific genetic markers for an Enterobacter hormaechei outbreak strain (EHOS) that caused a nationwide outbreak in The Netherlands. Most EHOS isolates carried a large conjugative plasmid (pQC) containing genes encoding heavy-metal resistance, mobile elements, pili-associated proteins and exported proteins as well as multiple-resistance genes. Furthermore, the chromosomally encoded high-pathogenicity island (HPI) was highly associated with the EHOS strain. In addition, other DNA fragments were identified that were associated with virulence: three DNA fragments known to be located on a virulence plasmid (pLVPK), as well as phage-and plasmid-related sequences. Also, four DNA fragments encoding putative pili with the most homology to pili of Salmonella enterica were associated with the EHOS. Finally, four DNA fragments encoding putative outer-membrane proteins were negatively associated with the EHOS. In conclusion, resistance and putative virulence genes were identified in the EHOS that may have contributed to increased epidemicity. The high number of genes detected in the EHOS that were related to transferable elements reflects the genomic plasticity of the E. cloacae complex and may explain the emergence of the EHOS in the hospital environment. INTRODUCTIONIn the pre-antibiotic era, isolates of the Enterobacter cloacae complex were not detected in surveys of nosocomial bacteria; they were first described as nosocomial pathogens in the 1970s (Sanders & Sanders, 1997). In 2001, Enterobacter spp. caused 7 % of nosocomial infections in intensive care units in the USA (Jones, 2003;Streit et al., 2004). Therefore, the E. cloacae complex can be considered as an emerging pathogen, of which Enterobacter hormaechei is the most commonly isolated nosocomial pathogen (Delmas et al., 2006;Paauw et al., 2008). A nationwide outbreak occurred with an E. hormaechei outbreak strain (EHOS) in The Netherlands . This strain disseminated throughout hospitals despite adequate implementation of internationally accepted infection-prevention guidelines and caused invasive infections in more than 100 patients (Paauw et al., 2007). Previous studies showed that most EHOS isolates carried the conjugative plasmid pQC, with several complex integrons containing aadB, bla CTX-M-9 and qnrA1 genes that encoded resistance to aminoglycosides and thirdgeneration cephalosporins, and reduced susceptibility to fluoroquinolones, respectively . However, it was also shown that other Enterobacteriaceae including other E. cloacae complex isolates with the pQC did not become highly epidemic like the EHOS (Paauw et al., 2007). Furthermore, of aminoglycoside-susceptible E. cloa...

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Section: Discussionsupporting

confidence: 80%

Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain

Paauw

Caspers²,

Hall

et al. 2009

Microbiology

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“…scn (staphylococcal complement inhibitor) encodes an inhibitor of complement formation that reduces phagocytosis by neutrophils. Rooijakkers et al (2005) showed that scn is human specific and does not affect cow, goat or sheep complement. chp (chemotaxis inhibitory protein) encodes a modulator of chemokine responses that prevents neutrophil chemotaxis and activation.…”

Section: Human (N535)mentioning

confidence: 99%

Staphylococcus aureus host specificity: comparative genomics of human versus animal isolates by multi-strain microarray

2008

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Staphylococcus aureus is a commensal and pathogen of several mammalian species, particularly humans and cattle. We aimed to (i) identify S. aureus genes associated with host specificity, (ii) determine the relatedness of human and animal isolates, and (iii) identify whether human and animal isolates typically exchanged mobile genetic elements encoding virulence and resistance genes. Using a well-validated seven-strain S. aureus microarray, we compared 56 UK S. aureus isolates that caused infection in cows, horses, goats, sheep and a camel with 161 human S. aureus isolates from healthy carriers and community acquired infections in the UK. We had previously shown that human isolates are clustered into ten dominant and a few minor lineages, each with unique combinations of surface proteins predicted to bind to human proteins. We found that the animal-associated S. aureus clustered into ten lineages, with 61 % assigned to four lineages, ST151, ST771, ST130 and ST873, that were unique to animals. The majority of bovine mastitis was caused by isolates of lineage ST151, ST771 and ST97, but a few human lineages also caused mastitis. S. aureus isolated from horses were more likely to cluster into humanassociated lineages, with 54 % of horse-associated S. aureus assigned to the human clusters CC1, CC8 and CC22; along with the presence of some multi-drug resistant strains, this suggests a human origin. This is the most comprehensive genetic comparison of human versus animal S. aureus isolates conducted, and because we used a whole-genome approach we could estimate the key genes with the greatest variability that are associated with host specificity. Several genes conserved in all human isolates were variable or missing in one or more animal lineages, including the well-characterized lineage specific genes fnbA, fnbB and coa. Interestingly, genes carried on mobile genetic elements (MGEs) such as chp, scn and sak were less common in animal S. aureus isolates, and bap was not found. There was a lot of MGE variation within lineages, and some evidence that exchange of MGEs such as bacteriophage and pathogenicity islands between animal and human lineages is feasible, but there was less evidence of antibiotic resistance gene transfer on the staphylococcal cassette chromosomes (SCC) or plasmids. Surprisingly, animal lineages are closely related to human lineages and only a handful of genes or gene combinations may be responsible for host specificity.

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“…The increased prevalence of MRSA infections and corresponding rise in life-threatening syndromes have made it imperative to elucidate the mechanisms of pathogenesis for S. aureus. The interaction between S. aureus and the host is complex and is mediated by an array of bacterial proteins that both mediate the various pathologies and modify the immune system of the host (4)(5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1

Ramsland

Willoughby

Trist

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

104

102

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Infection by Staphylococcus aureus can result in severe conditions such as septicemia, toxic shock, pneumonia, and endocarditis with antibiotic resistance and persistent nasal carriage in normal individuals being key drivers of the medical impact of this virulent pathogen. In both virulent infection and nasal colonization, S. aureus encounters the host immune system and produces a wide array of factors that frustrate host immunity. One in particular, the prototypical staphylococcal superantigen-like protein SSL7, potently binds IgA and C5, thereby inhibiting immune responses dependent on these major immune mediators. We report here the three-dimensional structure of the complex of SSL7 with Fc of human IgA1 at 3.2 Å resolution. Two SSL7 molecules interact with the Fc (one per heavy chain) primarily at the junction between the C␣2 and C␣3 domains. The binding site on each IgA chain is extensive, with SSL7 shielding most of the lateral surface of the C␣3 domain. However, the SSL7 molecules are positioned such that they should allow binding to secretory IgA. The key IgA residues interacting with SSL7 are also bound by the leukocyte IgA receptor, Fc␣RI (CD89), thereby explaining how SSL7 potently inhibits IgAdependent cellular effector functions mediated by Fc␣RI, such as phagocytosis, degranulation, and respiratory burst. Thus, the ability of S. aureus to subvert IgA-mediated immunity is likely to facilitate survival in mucosal environments such as the nasal passage and may contribute to systemic infections.Staphylococcus aureus is an important human pathogen causing conditions ranging from minor superficial skin infections to life-threatening syndromes, including sepsis, toxic shock syndrome, osteomyelitis, pneumonitis, and endocarditis. It is carried without symptoms in at least 20% of individuals (1, 2). The emergence in the 1960s of pandemic penicillin-resistant S. aureus has been followed by a variety of hospital-associated and community-associated methicillin-resistant strains (HA-and CA-MRSA) (2, 3). The increased prevalence of MRSA infections and corresponding rise in life-threatening syndromes have made it imperative to elucidate the mechanisms of pathogenesis for S. aureus. The interaction between S. aureus and the host is complex and is mediated by an array of bacterial proteins that both mediate the various pathologies and modify the immune system of the host (4-10).SSL7 (formerly named SET1) is the first described member of a new family of putative S. aureus toxins, the staphylococcal superantigen-like (SSL) proteins (11, 12), related to the staphylococcal enterotoxins (SEs) or superantigens (13). The SSL proteins have Ϸ30% sequence identity with toxic shock syndrome 1 (TSST-1) and 25% or less identity with other SEs. Despite the sequence differences, the SSL proteins have a typical SE tertiary structure consisting of a distinct oligonucleotide/oligosaccharide binding (OB-fold) linked to a ␤-grasp domain (14 -16).Similar to the se genes, the ssl genes are located in a pathogenicity island (SaPIn2) and ...

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Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases

Cited by 373 publications

References 42 publications

Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain

Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain

Staphylococcus aureus host specificity: comparative genomics of human versus animal isolates by multi-strain microarray

Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1

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