Staphylococcus aureus nasal carriage in Ukraine: antibacterial resistance and virulence factor encoding genes

Nasal colonization is the cause of recurrent staphylococcal infections. The host tissue colonization by Staphylococcus (S.) aureus is an important factor in disease pathogenesis. S. aureus expresses Fibronectin-Binding Protein A (FnBPA), which mediates the adhesion to fibrinogen, elastin and fibronectin [1]. The pathogenicity of S. aureus results from its ability to produce specific toxins and hydrolytic enzymes. Some S. aureus strains can produce Panton-Valentine Leucocidin (PVL), which can cause tissue necrosis and leukocyte lysis [2]. PVL is a bi-component leucotoxin composed of S-related and F-related proteins that are separately secreted, but act synergistically. The Exfoliative Toxins (ET) may cause the staphylococcal scalded-skin syndrome, Ritter disease, and bullous impetigo [3]. Three serological forms of ET, i.e. ETA, ETB and ETD have been linked to human pathologies [4]. The investigation into S. aureus antimicrobial susceptibility pattern presents a research question for national public health programs in Europe and other countries [5–9]. Increasing resistance to antibiotics and the growing prevalence of Methicillin Resistant S. aureus (MRSA) can be connected to antibiotic overuse in primary care and requires to be addressed promptly [10, 11]. Ukraine is not part of the European Union (EU), but it borders several EU countries. Ukrainian doctors have limited access to international information and do not take part in European research programs on epidemiology or bacterial drug resistance. Up to now, there has been only a report in 2009 on the antimicrobial susceptibility pattern of S. aureus, cultured from clinical samples in 97 surgical wards located in Ukraine [12]. In this study, the prevalence of MRSA ranged from 10.8% to 84.1% depending on the location. The authors reported that it was not possible to evaluate the general consumption of antibiotics outside the hospital environment, since they could be purchased without medical prescription. The aim of our study was (1) to assess the S. aureus nasal carriage rate including MRSA strains in adult Ukrainian population, (2) to determine the antibiotic resistant pattern and (3) the occurrence of PVL-, FnBPA- and ET-encoding genes.

There is no evidence of S. aureus susceptibility and occurrence of virulence encoding genes within the Ukrainian population. The present study reports that the prevalence of S. aureus nasal carriage in Ukraine was 40.4%, whereas MRSA carriage was 3.7%. In general, S. aureus nasal carriage rate in Ukraine is higher than in most countries in Europe, Africa, Asia, North and South America and Oceania [5–7, 18–23]. In our study, neither MSSA nor MRSA ciprofloxacin resistant strains were observed using the disk diffusion method. These data differ from the data concerning other countries [5, 7, 18, 23]. The absence of ciprofloxacin resistant strains can be explained by their limited use in Ukraine. In this study the ET-encoding genes were found in about 40% of S. aureus strains. The most prevalent serotype was ETD. Our data differ from the data concerning other European, American, and African countries, where the ETA serotype is prevalent and detected in more than 80% of toxin-producing strains [24–26]. Only in Japan, ETB-producing strains are more prevalent than those expressing ETA [27]. In this study, no significant difference was detected in the occurrence of ET-encoding genes between MRSA and MSSA. Other studies have suggested that the etb gene was found primarily in strains with mecA, while the eta gene was mainly found in strains without mecA[15]. The prevalence of fnbA-positive S. aureus in healthy Ukrainian adults is lower, if compared to its prevalence in other countries [28]. In the present study, FnBPA-encoding gene was detected in over 59% of strains, whereas the occurrence of the fnbA gene was more frequent in the MSSA. We found a high prevalence of PVL encoding genes. Over 58% strains isolated from nares in individuals with no staphylococcal infection symptoms, were luk-PV-positive. This evidence contrasts with previous reports. For instance, the prevalence of PVL-positive S. aureus nasal colonization in Dutch general practice patients was 0.6% [5]. Furthermore, a PVL prevalence of 38.9% was observed in S. aureus and it caused abscesses, arthritis, and soft-tissue infections [5]. The prevalence of PVL-positive S. aureus in nasal colonization was 2.4% in the United States. The data were obtained as part of the National Health and Nutrition Examination Survey [6]. It was estimated that PVL-positive S. aureus was more prevalent pathogen in the tropics and subtropics, if compared with European countries [29]. The PVL genes were detected in 10.6% methicillin sensitive S. aureus strains in the Indonesian population [30]. A similar PVL-positive percentage (around 57%) was discovered in an African study of five cities in Cameroon, Morocco, Madagascar, Niger and Senegal. However, the tested group consisted of individuals with an already diagnosed staphylococcal infection [31]. Therefore, the PVL-positive percentage in the Ukrainians with staphylococcal infection symptoms would be significantly higher. Travellers to tropical and subtropical countries are exposed to a higher risk of skin and soft-tissue infections. This phenomenon results from a higher PVL-positive S. aureus occurrence in tropical and subtropical countries [31]. Similarly, job seekers travelling from Ukraine could be a source of toxin-producing strains.

In our cohort of Ukrainian patients, we found that the prevalence of S. aureus nasal carriage was 40.4%. 9.1% of the strains were classified as MRSA and all MRSA isolates tested positive for the mecA gene. The prevalence of nasal MRSA was 3.7%. We also found a high prevalence of PVL- and ET-encoding genes among S. aureus nasal carriage strains. A limitation of our study is that we studied isolates deriving only from the South-West Ukraine and it cannot be representative of the overall Ukrainian situation. Furthermore, we did not perform spa typing and therefore we could not discriminate among different strains of S. aureus. Further studies are required to address those limitations. A systematic surveillance system can help prevent transmission and spread of drug resistant toxin producing S. aureus strains.