J Infect Chemother xxx (2014) 1e3
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Note
Methicillin-susceptible Staphylococcus aureus CC398: First description in prosthetic joint infection and genetic background comparison with nasal carriage isolatesq Guillaume G. Aubin a, b, Didier Lepelletier a, b, Alain Reynaud a, b, Jean-Philippe Lavigne c, d, Stéphane Corvec a, b, * a
EA3826, Thérapeutiques cliniques et expérimentales des infections e Faculté de Médecine, Nantes, France Service de Bactériologie-Hygiène hospitalière, CHU de Nantes, France INSERM U1047, Université de Montpellier 1, Nîmes, France d Laboratoire de Bactériologie, CHU Carémeau, Nîmes, France b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 28 January 2014 Received in revised form 28 February 2014 Accepted 3 March 2014
Few reports described infections with CC398 methicillin-susceptible Staphylococcus aureus (MSSA). We compared the genetic background of CC398 MSSA strains from nasal carriage and knee arthroplasty infection. DNA microarray analysis shows acquisition of particular adhesin, iron capture system and immune defense evasion mechanisms. These characteristics could explain pathogenesis in this type of infection. Ó 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Livestock associated Staphylococcus aureus CC398 Prosthetic-related infection DNA microarray
In the recent years, compared to hospital and communityacquired methicillin-resistant Staphylococcus aureus (MRSA), livestock has been described as a third MRSA reservoir, notably due to the worldwide spread of clonal complex 398 (CC398) MRSA strains [1e3]. However, little is known about CC398 methicillin-susceptible S. aureus (MSSA) isolates. Currently, CC398 MRSA/MSSA isolates are described in various hospital infections including skin and soft tissue infections, abscesses, and urinary tract infections [4,5]. Rare cases of severe infections such as endocarditis or bacteremia were reported, typically in older patients with underlying diseases [6,7]. A recent epidemiological study retrieved CC398 MSSA strains mainly in skin and soft tissue infections and, in few cases, in bone and joint infections [4]. MRSA CC398 infections were mostly linked with pig farms [1] but occasionally some cases occurred in people without any
q This work was presented, in part, at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, 2012 in San Francisco. * Corresponding author. Institut de Biologie, Service de Bactériologie-Hygiène hospitalière, CHU de Nantes, 9 quai moncousu, 44093 Nantes Cedex 01, France. Tel.: þ33 02 40 08 39 55; fax: þ33 02 40 08 38 29. E-mail address: [email protected] (S. Corvec).
contact with livestock. Concerning CC398 MSSA strains in Europe, these isolates remained prevalent among pig breedings with about 25% of colonization rate, depending on the studies [8,9]. Nevertheless, the origin, the evolution and global spread of CC398 lineage had not been clarified yet. Recently, two studies reported that the CC398 MSSA clone was the original clone from which the MRSA livestock associated clones had emerged [2,4]. A high genetic diversity in S. aureus clinical strains has been previously described in nasal carriage isolates [10]. Interestingly, the same variability has been observed among S. aureus isolates involved in prosthetic joint infection (PJI) including the most frequent Sequence Type (ST) as ST30, ST45 and ST15 [10]. Nevertheless, although S. aureus represents one of the most common microorganism detected in PJI [11], to date no MSSA CC398 strain isolated in this context has been described. Furthermore, the endogenous or exogenous origin of PJI remains debated [12]. The present study investigates the proportion of CC398 S. aureus detected in PJI and in nasal S. aureus carriers with a microarray comparison of their genetic background. Between January 2007, 1st and December 2010, 31st, we collected all S. aureus strains involved in monomicrobial PJI (hip or knee arthroplasties) from patients hospitalized in orthopedic surgery wards at Nantes University Hospital (France). Each isolate was
http://dx.doi.org/10.1016/j.jiac.2014.03.007 1341-321X/Ó 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Aubin GG, et al., Methicillin-susceptible Staphylococcus aureus CC398: First description in prosthetic joint infection and genetic background comparison with nasal carriage isolates, J Infect Chemother (2014), http://dx.doi.org/10.1016/ j.jiac.2014.03.007
2
G.G. Aubin et al. / J Infect Chemother xxx (2014) 1e3
recovered from deep surgical sites of infection (i.e joint fluid, periprosthetic tissues, and bone biopsies). In addition, between January 2012, 1st and February 2012, 28th, we studied a nasal carriage S. aureus isolates collection obtained from nasal swabbing of 100 outpatients admitted to orthopedic surgery consultation and living in a French area with a high density of pig breeding. This study was approved by the institutional Ethical committee. Genus, species and antibiotic susceptibilities were determined using the Vitek2Ò system (bioMérieux, Marcy l’Etoile, France) and interpreted according to the EUCAST recommendations. To investigate S. aureus clinical strains, the Alere StaphyType DNA microarray was used according to protocols previously detailed [10]. This microarray screens 333 resistance and virulence genes. Sequence types of all isolates were determined by Multi-Locus Sequence Typing as previously reported [13]. Protein A (spa) typing was performed on CC398 isolates according to the recommendations of the Ridom Staph Type standard protocol and using the Ridom SpaServer, which automatically analyzes spa repeats and assigns spa-types (http://spa.ridom.de/index.shtml). During the study period, we analyzed 56 and 31 S. aureus strains isolated from human hip or knee arthroplasty infections and from nasal carriage of outpatients in the orthopedic unit, respectively. PJI isolates came from 29 women and 27 men. Mean age was 73 years (range 21e96). 38% of patients suffered of arthritis before prosthetic implantation. S. aureus clinical strains involved in PJI belonged to 17 different CC. CC30, 5, 8, 45 and 15 were predominant (20, 20, 15, 12 and 7%, respectively). Nasal carriage sex ratio was 1.2 (17 men vs 14 women). No outpatient admitted to orthopedic surgery consultation had S. aureus infection 12 months before nasal sampling. The frequency of S. aureus nasal carriage was in accordance with previous studies [10]. CC30, 5 and 15 were predominant among nasal carriage isolates (23, 16 and 16% respectively). The proportion of CC398 clone was 1.8% (n ¼ 1) for PJI and 12.9% (n ¼ 4) in nasal carriers. This unexpected high rate of CC398 nasal carriage differed from other European country results [1,13] but was in accordance with a recent French study [4]. The CC398 S. aureus strain detected in PJI was isolated from a total knee arthroplasty (TKA). This late hematogenous infection occurred 9 years after knee prosthesis implantation in an 81 year-old woman. No source (portal of entry) of infection was identified and no contact with livestock was found. These five CC398 S. aureus isolates were all methicillinsusceptible but resistant to tetracycline. Price et al. suggested that tetracycline resistance may be acquired in livestock [2]. The only CC398 clinical strain was also resistant to erythromycin, likely due to ermT gene as ermA, ermB and ermC genes were not present according to microarray analysis [14]. CC398 strains were characterized by some features regarding the distribution of virulence factors: all isolates carried genes encoding chemotaxis inhibitory protein (chp) and staphylococcal complement inhibitor (scn) on a mobile genetic element belonging to the immune evasion cluster and beta-hemolysin-converting bacteriophages. These genes suggested a human origin of the clone, because these virulence factors show only an activity against the human innate immune system [3]. Both genes probably facilitate prolonged colonization in humans and may contribute to bacterial pathogenesis at the time of infection [3]. Recently, epidemiological and genetic characterization of CC398 S. aureus strains isolated in various infections such as skin and soft tissue infections, bacteremia and pneumonia confirmed that both genes (scn and chp) were specific to CC398 lineage [4]. Bone-binding sialoprotein (bbp), collagen-binding adhesion (cna) and intracellular adhesion (icaACD) genes, considered to take a prominent part in the pathogenesis of PJI, were also present in all strains [10]. Overall, the CC398 strains detected in this study
presented the same phenotypic and genotypic characteristics as previously described for CC398 MSSA strains [4]. On the other hand, few genes were exclusively present in the clinical strain involved in a PJI (Table 1). These genes could promote a switch from colonization to infection. The first gene that was detected exclusively in MSSA CC398 isolated from PJI was sdrC (encoding for a fibrinogen binding protein). The resulting adhesin could improve bone matrix binding [15]. Second, the use of iron as an enzymatic cofactor is pervasive in biological systems. Pathogenic bacteria such as S. aureus require iron to survive and replicate. Therefore, the presence of a particular allele of the heme-binding protein (isdA) in the clinical isolate could provide a specific hemosiderin with increased affinity [16]. Finally, staphylococcal superantigen-like (SSL) proteins are potent immune evasion molecules that specifically interact with various parts of the innate immune system [17]. The clinical TKA isolate possessed particular alleles of SSL protein 3 and 21, which may promote invasion and persistence of the infection. These virulence factors (sdrC, isdA and SSL genes) act in synergy with a local host defense impairment ending to hematogenous foreign body infection. This feature may improve adaptation to the human host, leading to a future epidemiological success of CC398 MSSA strain persistence. Interestingly, spa-typing revealed different types among these five strains. Nevertheless, two colonization strains and the clinical one belonged to the same spa-type, t571, according to the spa-type website. The low number of CC398 isolates analyzed was the main limitation of this work. Further larger studies including more CC398 strains are needed to confirm these hypotheses. Until recently, CC398 MSSA strains have been rarely found among S. aureus isolates identified in studies of colonization in humans or livestock. CC398 MSSA lineage emergence was confirmed in different infectious diseases such as bacteremia, infective endocarditis and prosthetic joint infections. Little is known about CC398 MSSA strains compared with livestock associated MRSA CC398 strains [1], the circumstances of their human adaptation remain to be elucidated. The high proportion of CC398 nasal carriers observed here increases the need to awareness of the CC398 MSSA dynamic transmission. The identification of three
Table 1 Genetic background comparison between nasal carriage and total knee arthroplasty infection by clonal complex 398 Staphylococcus aureus isolates. Genes detected
Resistance genes mecA Virulence genes agr regulator MSCRAMM bone-binding sialoprotein (bbp) collagen-binding adhesin (cna) Others icaACD chemotaxis inhibitor protein (chp) staphylococcal complement inhibitor (scn) sdrC fibrinogen binding protein (sdrC) heme/transferrin-binding protein (isdA) staphylococcal superantigen-like protein 3 and 21 (ssl) Spa-typing a
Isolates from nasal carriage n¼4
Isolate from prosthetic joint infection n¼1
agr I
agr I
þ þ
þ þ
þ þ
þ þ
þ
þ
þ
þ
þ
t571a, t12453, t3085
t571
Two strains belonged to spa-type 571.
Please cite this article in press as: Aubin GG, et al., Methicillin-susceptible Staphylococcus aureus CC398: First description in prosthetic joint infection and genetic background comparison with nasal carriage isolates, J Infect Chemother (2014), http://dx.doi.org/10.1016/ j.jiac.2014.03.007
G.G. Aubin et al. / J Infect Chemother xxx (2014) 1e3
candidate genes facilitating human prosthetic joint infections could be an indication for their potential role in the virulence. Conflict of interest None. Acknowledgments This study was supported by a grant number WS1106649 from Pfizer, France. We thank Pr. Gouin for allowing us to collect samples from orthopedic outpatients. References [1] Van Belkum A, Melles DC, Peeters JK, van Leeuwen WB, van Duijkeren E, Huijsdens XW, et al. Methicillin-resistant and -susceptible Staphylococcus aureus sequence type 398 in pigs and humans. Emerg Infect Dis 2008;14:479e83. [2] Price LB, Stegger M, Hasman H, Aziz M, Larsen J, Andersen PS, et al. Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock. MBio 2012;3:e305e11. [3] Fluit AC. Livestock-associated Staphylococcus aureus. Clin Microbiol Infect 2012;18:735e44. [4] Chroboczek T, Boisset S, Rasigade J-P, Tristan A, Bes M, Meugnier H, et al. Clonal complex 398 methicillin susceptible Staphylococcus aureus: a frequent unspecialized human pathogen with specific phenotypic and genotypic characteristics. PLoS One 2013;8:e68462. [5] Welinder-Olsson C, Florén-Johansson K, Larsson L, Oberg S, Karlsson L, Ahrén C. Infection with Panton-Valentine leukocidin-positive methicillinresistant Staphylococcus aureus t034. Emerg Infect Dis 2008;14:1271e2. [6] Schijffelen MJ, Boel CHE, van Strijp JAG, Fluit AC. Whole genome analysis of a livestock-associated methicillin-resistant Staphylococcus aureus ST398 isolate from a case of human endocarditis. BMC Genomics 2010;11:376.
3
[7] Van der Mee-Marquet N, François P, Domelier-Valentin A-S, Coulomb F, Decreux C, Hombrock-Allet C, et al. Emergence of unusual bloodstream infections associated with pig-borne-like Staphylococcus aureus ST398 in France. Clin Infect Dis 2011;52:152e3. [8] Hasman H, Moodley A, Guardabassi L, Stegger M, Skov RL, Aarestrup FM. Spa type distribution in Staphylococcus aureus originating from pigs, cattle and poultry. Vet Microbiol 2010;141:326e31. [9] Vandendriessche S, Vanderhaeghen W, Larsen J, de Mendonça R, Hallin M, Butaye P, et al. High genetic diversity of methicillin-susceptible Staphylococcus aureus (MSSA) from humans and animals on livestock farms and presence of SCCmec remnant DNA in MSSA CC398. J Antimicrob Chemother 2014;69: 355e62. [10] Aamot HV, Blomfeldt A, Skråmm I, Müller F, Monecke S. Molecular characterisation of methicillin-sensitive Staphylococcus aureus from deep surgical site infections in orthopaedic patients. Eur J Clin Microbiol Infect Dis 2012;31: 1999e2004. [11] Corvec S, Portillo ME, Pasticci BM, Borens O, Trampuz A. Epidemiology and new developments in the diagnosis of prosthetic joint infection. Int J Artif Organs 2012;35:923e34. [12] Berthelot P, Grattard F, Cazorla C, Passot J-P, Fayard J-P, Meley R, et al. Is nasal carriage of Staphylococcus aureus the main acquisition pathway for surgicalsite infection in orthopaedic surgery? Eur J Clin Microbiol Infect Dis 2010;29:373e82. [13] Lozano C, Gómez-Sanz E, Benito D, Aspiroz C, Zarazaga M, Torres C. Staphylococcus aureus nasal carriage, virulence traits, antibiotic resistance mechanisms, and genetic lineages in healthy humans in Spain, with detection of CC398 and CC97 strains. Int J Med Microbiol 2011;301:500e5. [14] Vandendriessche S, Kadlec K, Schwarz S, Denis O. Methicillin-susceptible Staphylococcus aureus ST398-t571 harbouring the macrolide-lincosamidestreptogramin B resistance gene erm(T) in Belgian hospitals. J Antimicrob Chemother 2011;66:2455e9. [15] Peacock SJ, Moore CE, Justice A, Kantzanou M, Story L, Mackie K, et al. Virulent combinations of adhesin and toxin genes in natural populations of Staphylococcus aureus. Infect Immun 2002;70:4987e96. [16] Haley KP, Skaar EP. A battle for iron: host sequestration and Staphylococcus aureus acquisition. Microbes Infect 2012;14:217e27. [17] Fraser JD, Proft T. The bacterial superantigen and superantigen-like proteins. Immunol Rev 2008;225:226e43.
Please cite this article in press as: Aubin GG, et al., Methicillin-susceptible Staphylococcus aureus CC398: First description in prosthetic joint infection and genetic background comparison with nasal carriage isolates, J Infect Chemother (2014), http://dx.doi.org/10.1016/ j.jiac.2014.03.007
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Note
Methicillin-susceptible Staphylococcus aureus CC398: First description in prosthetic joint infection and genetic background comparison with nasal carriage isolatesq Guillaume G. Aubin a, b, Didier Lepelletier a, b, Alain Reynaud a, b, Jean-Philippe Lavigne c, d, Stéphane Corvec a, b, * a
EA3826, Thérapeutiques cliniques et expérimentales des infections e Faculté de Médecine, Nantes, France Service de Bactériologie-Hygiène hospitalière, CHU de Nantes, France INSERM U1047, Université de Montpellier 1, Nîmes, France d Laboratoire de Bactériologie, CHU Carémeau, Nîmes, France b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 28 January 2014 Received in revised form 28 February 2014 Accepted 3 March 2014
Few reports described infections with CC398 methicillin-susceptible Staphylococcus aureus (MSSA). We compared the genetic background of CC398 MSSA strains from nasal carriage and knee arthroplasty infection. DNA microarray analysis shows acquisition of particular adhesin, iron capture system and immune defense evasion mechanisms. These characteristics could explain pathogenesis in this type of infection. Ó 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Livestock associated Staphylococcus aureus CC398 Prosthetic-related infection DNA microarray
In the recent years, compared to hospital and communityacquired methicillin-resistant Staphylococcus aureus (MRSA), livestock has been described as a third MRSA reservoir, notably due to the worldwide spread of clonal complex 398 (CC398) MRSA strains [1e3]. However, little is known about CC398 methicillin-susceptible S. aureus (MSSA) isolates. Currently, CC398 MRSA/MSSA isolates are described in various hospital infections including skin and soft tissue infections, abscesses, and urinary tract infections [4,5]. Rare cases of severe infections such as endocarditis or bacteremia were reported, typically in older patients with underlying diseases [6,7]. A recent epidemiological study retrieved CC398 MSSA strains mainly in skin and soft tissue infections and, in few cases, in bone and joint infections [4]. MRSA CC398 infections were mostly linked with pig farms [1] but occasionally some cases occurred in people without any
q This work was presented, in part, at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, 2012 in San Francisco. * Corresponding author. Institut de Biologie, Service de Bactériologie-Hygiène hospitalière, CHU de Nantes, 9 quai moncousu, 44093 Nantes Cedex 01, France. Tel.: þ33 02 40 08 39 55; fax: þ33 02 40 08 38 29. E-mail address: [email protected] (S. Corvec).
contact with livestock. Concerning CC398 MSSA strains in Europe, these isolates remained prevalent among pig breedings with about 25% of colonization rate, depending on the studies [8,9]. Nevertheless, the origin, the evolution and global spread of CC398 lineage had not been clarified yet. Recently, two studies reported that the CC398 MSSA clone was the original clone from which the MRSA livestock associated clones had emerged [2,4]. A high genetic diversity in S. aureus clinical strains has been previously described in nasal carriage isolates [10]. Interestingly, the same variability has been observed among S. aureus isolates involved in prosthetic joint infection (PJI) including the most frequent Sequence Type (ST) as ST30, ST45 and ST15 [10]. Nevertheless, although S. aureus represents one of the most common microorganism detected in PJI [11], to date no MSSA CC398 strain isolated in this context has been described. Furthermore, the endogenous or exogenous origin of PJI remains debated [12]. The present study investigates the proportion of CC398 S. aureus detected in PJI and in nasal S. aureus carriers with a microarray comparison of their genetic background. Between January 2007, 1st and December 2010, 31st, we collected all S. aureus strains involved in monomicrobial PJI (hip or knee arthroplasties) from patients hospitalized in orthopedic surgery wards at Nantes University Hospital (France). Each isolate was
http://dx.doi.org/10.1016/j.jiac.2014.03.007 1341-321X/Ó 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Aubin GG, et al., Methicillin-susceptible Staphylococcus aureus CC398: First description in prosthetic joint infection and genetic background comparison with nasal carriage isolates, J Infect Chemother (2014), http://dx.doi.org/10.1016/ j.jiac.2014.03.007
2
G.G. Aubin et al. / J Infect Chemother xxx (2014) 1e3
recovered from deep surgical sites of infection (i.e joint fluid, periprosthetic tissues, and bone biopsies). In addition, between January 2012, 1st and February 2012, 28th, we studied a nasal carriage S. aureus isolates collection obtained from nasal swabbing of 100 outpatients admitted to orthopedic surgery consultation and living in a French area with a high density of pig breeding. This study was approved by the institutional Ethical committee. Genus, species and antibiotic susceptibilities were determined using the Vitek2Ò system (bioMérieux, Marcy l’Etoile, France) and interpreted according to the EUCAST recommendations. To investigate S. aureus clinical strains, the Alere StaphyType DNA microarray was used according to protocols previously detailed [10]. This microarray screens 333 resistance and virulence genes. Sequence types of all isolates were determined by Multi-Locus Sequence Typing as previously reported [13]. Protein A (spa) typing was performed on CC398 isolates according to the recommendations of the Ridom Staph Type standard protocol and using the Ridom SpaServer, which automatically analyzes spa repeats and assigns spa-types (http://spa.ridom.de/index.shtml). During the study period, we analyzed 56 and 31 S. aureus strains isolated from human hip or knee arthroplasty infections and from nasal carriage of outpatients in the orthopedic unit, respectively. PJI isolates came from 29 women and 27 men. Mean age was 73 years (range 21e96). 38% of patients suffered of arthritis before prosthetic implantation. S. aureus clinical strains involved in PJI belonged to 17 different CC. CC30, 5, 8, 45 and 15 were predominant (20, 20, 15, 12 and 7%, respectively). Nasal carriage sex ratio was 1.2 (17 men vs 14 women). No outpatient admitted to orthopedic surgery consultation had S. aureus infection 12 months before nasal sampling. The frequency of S. aureus nasal carriage was in accordance with previous studies [10]. CC30, 5 and 15 were predominant among nasal carriage isolates (23, 16 and 16% respectively). The proportion of CC398 clone was 1.8% (n ¼ 1) for PJI and 12.9% (n ¼ 4) in nasal carriers. This unexpected high rate of CC398 nasal carriage differed from other European country results [1,13] but was in accordance with a recent French study [4]. The CC398 S. aureus strain detected in PJI was isolated from a total knee arthroplasty (TKA). This late hematogenous infection occurred 9 years after knee prosthesis implantation in an 81 year-old woman. No source (portal of entry) of infection was identified and no contact with livestock was found. These five CC398 S. aureus isolates were all methicillinsusceptible but resistant to tetracycline. Price et al. suggested that tetracycline resistance may be acquired in livestock [2]. The only CC398 clinical strain was also resistant to erythromycin, likely due to ermT gene as ermA, ermB and ermC genes were not present according to microarray analysis [14]. CC398 strains were characterized by some features regarding the distribution of virulence factors: all isolates carried genes encoding chemotaxis inhibitory protein (chp) and staphylococcal complement inhibitor (scn) on a mobile genetic element belonging to the immune evasion cluster and beta-hemolysin-converting bacteriophages. These genes suggested a human origin of the clone, because these virulence factors show only an activity against the human innate immune system [3]. Both genes probably facilitate prolonged colonization in humans and may contribute to bacterial pathogenesis at the time of infection [3]. Recently, epidemiological and genetic characterization of CC398 S. aureus strains isolated in various infections such as skin and soft tissue infections, bacteremia and pneumonia confirmed that both genes (scn and chp) were specific to CC398 lineage [4]. Bone-binding sialoprotein (bbp), collagen-binding adhesion (cna) and intracellular adhesion (icaACD) genes, considered to take a prominent part in the pathogenesis of PJI, were also present in all strains [10]. Overall, the CC398 strains detected in this study
presented the same phenotypic and genotypic characteristics as previously described for CC398 MSSA strains [4]. On the other hand, few genes were exclusively present in the clinical strain involved in a PJI (Table 1). These genes could promote a switch from colonization to infection. The first gene that was detected exclusively in MSSA CC398 isolated from PJI was sdrC (encoding for a fibrinogen binding protein). The resulting adhesin could improve bone matrix binding [15]. Second, the use of iron as an enzymatic cofactor is pervasive in biological systems. Pathogenic bacteria such as S. aureus require iron to survive and replicate. Therefore, the presence of a particular allele of the heme-binding protein (isdA) in the clinical isolate could provide a specific hemosiderin with increased affinity [16]. Finally, staphylococcal superantigen-like (SSL) proteins are potent immune evasion molecules that specifically interact with various parts of the innate immune system [17]. The clinical TKA isolate possessed particular alleles of SSL protein 3 and 21, which may promote invasion and persistence of the infection. These virulence factors (sdrC, isdA and SSL genes) act in synergy with a local host defense impairment ending to hematogenous foreign body infection. This feature may improve adaptation to the human host, leading to a future epidemiological success of CC398 MSSA strain persistence. Interestingly, spa-typing revealed different types among these five strains. Nevertheless, two colonization strains and the clinical one belonged to the same spa-type, t571, according to the spa-type website. The low number of CC398 isolates analyzed was the main limitation of this work. Further larger studies including more CC398 strains are needed to confirm these hypotheses. Until recently, CC398 MSSA strains have been rarely found among S. aureus isolates identified in studies of colonization in humans or livestock. CC398 MSSA lineage emergence was confirmed in different infectious diseases such as bacteremia, infective endocarditis and prosthetic joint infections. Little is known about CC398 MSSA strains compared with livestock associated MRSA CC398 strains [1], the circumstances of their human adaptation remain to be elucidated. The high proportion of CC398 nasal carriers observed here increases the need to awareness of the CC398 MSSA dynamic transmission. The identification of three
Table 1 Genetic background comparison between nasal carriage and total knee arthroplasty infection by clonal complex 398 Staphylococcus aureus isolates. Genes detected
Resistance genes mecA Virulence genes agr regulator MSCRAMM bone-binding sialoprotein (bbp) collagen-binding adhesin (cna) Others icaACD chemotaxis inhibitor protein (chp) staphylococcal complement inhibitor (scn) sdrC fibrinogen binding protein (sdrC) heme/transferrin-binding protein (isdA) staphylococcal superantigen-like protein 3 and 21 (ssl) Spa-typing a
Isolates from nasal carriage n¼4
Isolate from prosthetic joint infection n¼1
agr I
agr I
þ þ
þ þ
þ þ
þ þ
þ
þ
þ
þ
þ
t571a, t12453, t3085
t571
Two strains belonged to spa-type 571.
Please cite this article in press as: Aubin GG, et al., Methicillin-susceptible Staphylococcus aureus CC398: First description in prosthetic joint infection and genetic background comparison with nasal carriage isolates, J Infect Chemother (2014), http://dx.doi.org/10.1016/ j.jiac.2014.03.007
G.G. Aubin et al. / J Infect Chemother xxx (2014) 1e3
candidate genes facilitating human prosthetic joint infections could be an indication for their potential role in the virulence. Conflict of interest None. Acknowledgments This study was supported by a grant number WS1106649 from Pfizer, France. We thank Pr. Gouin for allowing us to collect samples from orthopedic outpatients. References [1] Van Belkum A, Melles DC, Peeters JK, van Leeuwen WB, van Duijkeren E, Huijsdens XW, et al. Methicillin-resistant and -susceptible Staphylococcus aureus sequence type 398 in pigs and humans. Emerg Infect Dis 2008;14:479e83. [2] Price LB, Stegger M, Hasman H, Aziz M, Larsen J, Andersen PS, et al. Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock. MBio 2012;3:e305e11. [3] Fluit AC. Livestock-associated Staphylococcus aureus. Clin Microbiol Infect 2012;18:735e44. [4] Chroboczek T, Boisset S, Rasigade J-P, Tristan A, Bes M, Meugnier H, et al. Clonal complex 398 methicillin susceptible Staphylococcus aureus: a frequent unspecialized human pathogen with specific phenotypic and genotypic characteristics. PLoS One 2013;8:e68462. [5] Welinder-Olsson C, Florén-Johansson K, Larsson L, Oberg S, Karlsson L, Ahrén C. Infection with Panton-Valentine leukocidin-positive methicillinresistant Staphylococcus aureus t034. Emerg Infect Dis 2008;14:1271e2. [6] Schijffelen MJ, Boel CHE, van Strijp JAG, Fluit AC. Whole genome analysis of a livestock-associated methicillin-resistant Staphylococcus aureus ST398 isolate from a case of human endocarditis. BMC Genomics 2010;11:376.
3
[7] Van der Mee-Marquet N, François P, Domelier-Valentin A-S, Coulomb F, Decreux C, Hombrock-Allet C, et al. Emergence of unusual bloodstream infections associated with pig-borne-like Staphylococcus aureus ST398 in France. Clin Infect Dis 2011;52:152e3. [8] Hasman H, Moodley A, Guardabassi L, Stegger M, Skov RL, Aarestrup FM. Spa type distribution in Staphylococcus aureus originating from pigs, cattle and poultry. Vet Microbiol 2010;141:326e31. [9] Vandendriessche S, Vanderhaeghen W, Larsen J, de Mendonça R, Hallin M, Butaye P, et al. High genetic diversity of methicillin-susceptible Staphylococcus aureus (MSSA) from humans and animals on livestock farms and presence of SCCmec remnant DNA in MSSA CC398. J Antimicrob Chemother 2014;69: 355e62. [10] Aamot HV, Blomfeldt A, Skråmm I, Müller F, Monecke S. Molecular characterisation of methicillin-sensitive Staphylococcus aureus from deep surgical site infections in orthopaedic patients. Eur J Clin Microbiol Infect Dis 2012;31: 1999e2004. [11] Corvec S, Portillo ME, Pasticci BM, Borens O, Trampuz A. Epidemiology and new developments in the diagnosis of prosthetic joint infection. Int J Artif Organs 2012;35:923e34. [12] Berthelot P, Grattard F, Cazorla C, Passot J-P, Fayard J-P, Meley R, et al. Is nasal carriage of Staphylococcus aureus the main acquisition pathway for surgicalsite infection in orthopaedic surgery? Eur J Clin Microbiol Infect Dis 2010;29:373e82. [13] Lozano C, Gómez-Sanz E, Benito D, Aspiroz C, Zarazaga M, Torres C. Staphylococcus aureus nasal carriage, virulence traits, antibiotic resistance mechanisms, and genetic lineages in healthy humans in Spain, with detection of CC398 and CC97 strains. Int J Med Microbiol 2011;301:500e5. [14] Vandendriessche S, Kadlec K, Schwarz S, Denis O. Methicillin-susceptible Staphylococcus aureus ST398-t571 harbouring the macrolide-lincosamidestreptogramin B resistance gene erm(T) in Belgian hospitals. J Antimicrob Chemother 2011;66:2455e9. [15] Peacock SJ, Moore CE, Justice A, Kantzanou M, Story L, Mackie K, et al. Virulent combinations of adhesin and toxin genes in natural populations of Staphylococcus aureus. Infect Immun 2002;70:4987e96. [16] Haley KP, Skaar EP. A battle for iron: host sequestration and Staphylococcus aureus acquisition. Microbes Infect 2012;14:217e27. [17] Fraser JD, Proft T. The bacterial superantigen and superantigen-like proteins. Immunol Rev 2008;225:226e43.
Please cite this article in press as: Aubin GG, et al., Methicillin-susceptible Staphylococcus aureus CC398: First description in prosthetic joint infection and genetic background comparison with nasal carriage isolates, J Infect Chemother (2014), http://dx.doi.org/10.1016/ j.jiac.2014.03.007
