Staphylococcus aureus nasal carriers risk autoinfection; however, knowledge about the factors that make specific strains successful colonizers is limited. This study was undertaken to identify the most successful S. aureus clones in nasal carriers and compare their distribution among host groups. The population structure of S. aureus isolates from healthy adults was investigated by spa typing 1,981 isolates from persistent and intermittent nasal carriers participating in a health survey. In the baseline screening (1,113 isolates), the most common spa types were t012 (8.4%), t084 (7.6%), and t065 (4.9%). Three large spa clonal complexes (spa CC012, spa CC065, and spa CC084) comprised 62.4% of the isolates. In multivariate models adjusted for age and smoking status, male sex was associated with higher risk for spa type t084 (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.06 to 2.77), and lower risk of spa type t012 (OR, 0.60; 95% CI, 0.39 to 0.92) colonization. The prevalence of spa type t012 decreased significantly with increasing age (P ؍ 0.03), with a prevalence almost twice as high in the youngest group (age 30 to 44 years, prevalence ؍ 11.1%) as in the oldest group (age, 60 to 87 years; prevalence ؍ 5.6%). Among baseline isolates, spa type t084 had a twofold-higher prevalence among intermittent carriers than among persistent carriers (10.6% versus 5.5%; P ؍ 0.04). In summary, the two most prevalent spa types found in this study were significantly associated with age and/or gender. This may provide valuable clues to the multifactorial mechanisms, among them bacterial factors, involved in nasal colonization with S. aureus.
Signaling through Toll-like receptors (TLRs), crucial molecules in the induction of host defense responses, requires adaptor proteins that contain a Toll/interleukin-1 receptor (TIR) domain. The pathogen Staphylococcus aureus produces several innate immune-evasion molecules that interfere with the host's innate immune response. A database search analysis suggested the presence of a gene encoding a homologue of the human TIR domain in S. aureus MSSA476 which was named staphylococcal TIR domain protein (TirS). Ectopic expression of TirS in human embryonic kidney, macrophage and keratinocyte cell lines interfered with signaling through TLR2, including MyD88 and TIRAP, NF-κB and/or mitogen-activated protein kinase pathways. Moreover, the presence of TirS reduced the levels of cytokines MCP-1 and G-CSF secreted in response to S. aureus. The effects on NF-κB pathway were confirmed using S. aureus MSSA476 wild type, an isogenic mutant MSSA476ΔtirS, and complemented MSSA476ΔtirS +pTirS in a Transwell system where bacteria and host cells were physically separated. Finally, in a systematic mouse infection model, TirS promoted bacterial accumulation in several organs 4 days postinfection. The results of this study reveal a new S. aureus virulence factor that can interfere with PAMP-induced innate immune signaling in vitro and bacterial survival in vivo.
BackgroundObesity and diabetes mellitus (DM) have been linked to increased risk of infections, and Staphylococcus aureus nasal colonization is a major risk factor for developing infections with the microbe. We therefore sought to find whether body mass index (BMI) and waist circumference (WC) could be associated with S. aureus colonization independent of DM.Methodology S. aureus colonization was assessed by nasal swab cultures among 2,169 women and 1,709 men, aged 30–87 years, in the population-based Tromsø Staph and Skin Study in 2007–08. Height (cm), weight (kg), WC (cm), and glycated haemoglobin (HbA1c,%) were measured. Multivariable logistic regression analyses including information on DM, HbA1c, hormonal contraceptive use and other potential confounders were used.ResultsIn the female population, each 2.5 kg/m2 increase in BMI was associated with a 7% higher odds of S. aureus nasal colonization (P = 0.01). When comparing obese and lean women aged 30–43 years, we observed that BMI ≥32.5 versus <22.5 kg/m2 and WC ≥101 versus <80 cm was associated with a 2.60 and 2.12 times higher odds of S. aureus colonization, respectively (95% confidence intervals 1.35–4.98 and 1.17–3.85). Among men, high WC was also associated with S. aureus nasal colonization. The associations did not change significantly when the analysis was restricted to participants without signs of pre-diabetes (HbA1c <6.0%) among women and men, and to non-users of hormonal contraceptives among women.ConclusionOur results support that obesity is a possible determinant for S. aureus nasal colonization independent of DM, in particular for premenopausal women. The role of obesity at different ages and by sex should be addressed in future prospective studies of S. aureus colonization.
The human body is constantly challenged by a variety of commensal and pathogenic micro-organisms that trigger the immune system. Central in the first line of defence is the pattern-recognition receptor (PRR)-induced stimulation of the NFκB pathway, leading to NFκB activation. The subsequent production of pro-inflammatory cytokines and/or antimicrobial peptides results in recruitment of professional phagocytes and bacterial clearance. To overcome this, bacteria have developed mechanisms for targeted interference in every single step in the PRR–NFκB pathway to dampen host inflammatory responses. This review aims to briefly overview the PRR–NFκB pathway in relation to the immune response and give examples of the diverse bacterial evasion mechanisms including changes in the bacterial surface, decoy production and injection of effector molecules. Targeted regulation of inflammatory responses is needed and bacterial molecules developed for immune evasion could provide future anti-inflammatory agents.
SUMMARYHealthcare workers (HCWs) may be a reservoir for Staphylococcus aureus transmission to patients. We examined whether HCW status is associated with S. aureus nasal carriage and population structure (spa types) in 1302 women (334 HCWs) and 977 men (71 HCWs) aged 30–69 years participating in the population-based Tromsø Study in 2007–2008. Multivariable logistic regression models were used. While no methicillin-resistant S. aureus (MRSA) was isolated, overall, 26·2% of HCWs and 26·0% of non-HCWs were S. aureus nasal carriers. For women overall and women residing with children, the odds ratios for nasal carriage were 1·54 [95% confidence interval (CI) 1·09–2·19] and 1·86 (95% CI 1·14–3·04), respectively, in HCWs compared to non-HCWs. Moreover, HCWs vs. non-HCWs had a 2·17 and 3·16 times higher risk of spa types t012 and t015, respectively. This supports the view that HCWs have an increased risk of S. aureus nasal carriage depending on gender, family status and spa type.
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