Molecular epidemiology of Staphylococcus aureus strains isolated from inpatients with infected diabetic foot ulcers in an Algerian University Hospital

Djahmi, Nassima; Messad, N.; Nedjai, Sabrina; Moussaoui, Abdelfattah El; Mazouz, D.; Richard, Jean-Louis; Sotto, Albert; Lavigne, Jean‐Philippe

doi:10.1111/1469-0691.12199

Cited by 65 publications

(76 citation statements)

References 30 publications

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“…12 Moreover, recent epidemiological studies reveal that SEK is among the most prevalent superantigens in clinical isolates, particularly in methicillin resistant S. aureus (MRSA), and is thus far the only SE to be associated with CA-MRSA. 4,[13][14][15][16][17] We have previously shown that SEK was secreted by all examined S. aureus strains that encode the toxin (n D 36), and, in a murine soft-tissue infection model, we demonstrated that clinical isolates cause comparable accumulation of SEK within abscesses regardless of the amount of SEK they secrete in-vitro. 18 Here, we utilize our previously described SEK-binding mAbs to further explore the role of SEK in immune activation and disease.…”

Section: Introductionmentioning

confidence: 65%

Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced toxic shock and sepsis by USA300Staphylococcus aureus

et al. 2016

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Staphylococcus aureus is a leading infectious cause of life-threatening disease in humans, yet there is currently no vaccine to combat this bacterium. The pathogenesis of S. aureus is mediated by a diverse array of protein toxins including a large family of secreted pyrogenic superantigens. Neutralization of superantigens, including SEB and TSST-1, has proven to be protective in several animal models of toxic shock and sepsis. We demonstrate, for the first time, that a far more prevalent staphylococcal superantigen, SEK, can also induce lethal shock in mice. Additionally, we describe monoclonal antibodies (mAbs) that inhibit SEK-induced mitogenicity as well as protect against SEK-induced lethality, and enhance survival from S. aureus septicemia in murine models. MAb-4G3 (IgG2b), mAb-5G2 (IgG1), and mAb-9H2 (IgG1), all inhibit SEK-induced proliferation and cytokine production of human immune cells. We then demonstrate that passive immunization with a combination of mAb-4G3 and mAb-5G4, 2 mAbs that do not compete for epitope(s) on SEK, significantly enhance survival in a murine model of SEK-induced toxic shock (p D 0.006). In the setting of sepsis, passive immunization with this combination of mAbs also significantly enhances survival in mice after challenge with CA-MRSA strain USA300 (p D 0.03). Furthermore, septic mice that received mAb treatment in conjunction with vancomycin exhibit less morbidity than mice treated with vancomycin alone. Taken together, these findings suggest that the contribution of SEK to S. aureus pathogenesis may be greater than previously appreciated, and that adjunctive therapy with passive immunotherapy against SEs may be beneficial.

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Section: Introductionmentioning

confidence: 65%

Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced toxic shock and sepsis by USA300Staphylococcus aureus

et al. 2016

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“…isolated MRSA; they found the nasal carriage of S. aureus to be significantly associated with cancer and previous hospitalization for kidney failure due to immunological suppression and hemodialysis. The MRSA isolates ST239 ( n = 60), ST80 ( n = 27), ST5 ( n = 2), ST22 ( n = 2), and ST535 ( n = 1) harbored mecA . In another study in Algeria, typing of 64 MRSA isolated from human pus ( n = 47), venous catheters ( n = 7), tracheal aspirates ( n = 4), puncture fluids ( n = 3), blood ( n = 2), and urine ( n = 1) in 64 patients found that 50 were hospital‐acquired MRSA (HA‐MRSA) and 14 were community‐acquired MRSA (CA‐MRSA); mecA , mobilized by SCC mec , was the only detected mechanism of resistance.…”

Section: Resultsmentioning

confidence: 99%

Molecular epidemiology and mechanisms of antibiotic resistance inEnterococcusspp.,Staphylococcusspp., andStreptococcusspp. in Africa: a systematic review from a One Health perspective

Sekyere

Mensah

2019

Annals of the New York Academy of Sciences

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A systematic review of antibiotic‐resistant Gram‐positive bacteria in Africa from a One Health perspective is lacking. Here, we report result from a search for English‐language articles on the resistance mechanisms and clonality of Gram‐positive bacteria in Africa between 2007 and 2019 reported in PubMed, Web of Science, ScienceDirect, and African Journals OnLine; 172 studies from 22 different African countries were identified. Resistance genes, such as mecA, erm(B), erm(C), tet(M), tet(K), tet(L), vanB, vanA, vanC, and tet(O), were found to be common. Staphylococcus spp., Enterococcus spp., and Streptococcus spp. were the main species reported by the studies, with clones such as Staphylococcus aureus ST5 (n = 218 isolates), ST8 (n = 127 isolates), ST80 (n = 133 isolates), and ST88 (n = 117 isolates), and mobile genetic elements such as IS16 (n = 28 isolates), IS256 (n = 96), Tn916 (n = 107 isolates), and SCCmec (n = 4437 isolates) identified. SCCmec IV (n = 747 isolates) was predominant, followed by SCCmec III (n = 305 isolates), SCCmec II (n = 163 isolates), SCCmec V (n = 135 isolates), and SCCmec I (n = 79 isolates). Resistance to penicillin (n = 5926 isolates), tetracycline (n = 5300 isolates), erythromycin (n = 5151 isolates), rifampicin (n = 3823 isolates), gentamycin (n = 3494 isolates), sulfamethoxazole/trimethoprim (n = 3089 isolates), and ciprofloxacin (n = 2746 isolates) was common in most reports from 22 countries. Clonal dissemination of resistance across countries and between humans, animals, and the environment was observed. Resistance rates ranged from 1.4% to 100% for 15 of the studies; 10 were One Health–related studies. Strict infection control measures, antimicrobial stewardship, and periodic One Health epidemiological surveillance studies are needed to monitor and contain the threat of increasing antibiotic resistance in Africa.

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“…Several epidemiological studies have shown that sel-k is one of the most prevalent enterotoxin genes in clinical isolates of S. aureus (10,(12)(13)(14)(15)(16). Moreover, in several of these studies, SEl-K was significantly associated with CA-MRSA strains (10,15,16), which included USA300, USA400, and other clones.…”

Section: Discussionmentioning

confidence: 98%

“…One of these toxins, SEl-K, has been shown to exhibit superantigenic properties, including V␤-specific T cell activation, pyrogenicity, emesis, and lethality in primates (7)(8)(9). Epidemiological studies have demonstrated the SEl-K-encoding genes to be among the most common SE genes in S. aureus clinical isolates (10)(11)(12)(13)(14). Additionally, SEl-K is the only SE gene to our knowledge that is significantly associated with community-acquired methicillin-resistant S. aureus (CA-MRSA) strains of several clonal lineages (10,15,16).…”

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confidence: 99%

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

et al. 2014

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SEl-K is commonly present in more than half of all Staphylococcus aureus clinical isolates and is present in almost all USA300 community-acquired methicillin-resistant S. aureus (CA-MRSA) isolates. Sequencing of the sel-k gene in over 20 clinical isolates and comparative analysis with all 14 published sel-k sequences indicate that there are at least 6 variants of the sel-k gene, including one that is conserved among all examined USA300 strains. Additionally, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) that specifically detects and measures SEl-K protein in culture supernatants and biological fluids. Quantification of in vitro SEl-K secretion by various S. aureus isolates using this novel capture ELISA revealed detectable amounts of SEl-K secretion by all isolates, with the highest secretion levels being exhibited by MRSA strains that coexpress SEB. In vivo secretion was measured in a murine thigh abscess model, where similar levels of SEl-K accumulation were noted regardless of whether the infecting strain exhibited high or low secretion of SEl-K in vitro. We conclude that SEl-K is commonly expressed in the setting of staphylococcal infection, in significant amounts. SEl-K should be further explored as a target for passive immunotherapy against complicated S. aureus infection. Staphylococcus aureus can express a large and diverse repertoire of virulence factors, including many different surface proteins, enzymes, and secreted toxins (1). Among the most potent of these virulence factors are the members of a family of secreted, heatstable proteins known as enterotoxins. More than 20 staphylococcal enterotoxins (SEs) have been discovered that demonstrate superantigenic (SAg) properties against T cells (2, 3). Superantigens can activate 20% to 50% of the T cell population by bypassing the traditional pathway of major histocompatibility complex (MHC)-dependent presentation of antigens to T cell receptors (TCRs). Instead, superantigens bind simultaneously to MHC class II (MHC-II) and TCRs, outside their antigen-binding groove, resulting in an excessive inflammatory response that can lead to toxic shock, multiorgan failure, and death. Superantigens are also associated with other immune-mediated diseases, including Kawasaki disease, atopic dermatitis, and chronic rhinosinusitis (4).The classical superantigens toxic shock syndrome toxin 1 (TSST-1), SEA, and SEB have been extensively studied due to their causative roles in toxic shock syndrome and food poisoning (5). However, advancements in sequencing methodologies have enabled the discovery of many more SEs whose roles in pathogenesis remain unknown (6). One of these toxins, SEl-K, has been shown to exhibit superantigenic properties, including V␤-specific T cell activation, pyrogenicity, emesis, and lethality in primates (7-9). Epidemiological studies have demonstrated the SEl-K-encoding genes to be among the most common SE genes in S. aureus clinical isolates (10-14). Additionally, SEl-K is the only SE gene to our knowledge that is si...

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Molecular epidemiology of Staphylococcus aureus strains isolated from inpatients with infected diabetic foot ulcers in an Algerian University Hospital

Cited by 65 publications

References 30 publications

Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced toxic shock and sepsis by USA300Staphylococcus aureus

Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced toxic shock and sepsis by USA300Staphylococcus aureus

Molecular epidemiology and mechanisms of antibiotic resistance inEnterococcusspp.,Staphylococcusspp., andStreptococcusspp. in Africa: a systematic review from a One Health perspective

Detection and Measurement of Staphylococcal Enterotoxin-Like K (SEl-K) Secretion by Staphylococcus aureus Clinical Isolates

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