Role of Enterotoxin-Producing Staphylococci in Zoonotic Infections in Iran

© 2018 The Author(s); Published by Alborz University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. Context Typical opportunistic pathogens of coagulase positive Staphylococcus spp. are capable of causing a wide spectrum of different purulent and toxin-mediated diseases such as enteric infections.1 Staphylococcus intermedius is very similar to S. aureus in phenotypic characteristics and similarly produces enterotoxins.2-4 Pigment production, hemolysis, alkaline phosphatase and urease positive tests, mannitol and maltose fermentation and susceptibility to novobiocin and Polymyxin B are characteristics of S. intermedius.2,5 Originally regarded as a single species, molecular characterization has placed S. intermedius in a new classification as S. intermedius group (SIG), which includes S. intermedius, S. pseudintermedius, and S. delphini.6,7 These species cause diseases in human and animals (especially people who keep pets at home). S. aureus is a human commensal, while other coagulase positive species are present in animals. It has been revealed that S. intermedius mostly infects dogs (resides on the skin or mucosal surfaces).8 The general transferability of these species between pets and humans has increased during recent years.9,10 Staphylococcal species are able to express a wide spectrum of virulence factors, such as coagulase, cell wall components, hemolysins, proteases, enterotoxins, toxic-shock syndrome (TSS), and exfoliating toxins.11 Enterotoxins produced by these species are pyrogenic components not inactivated by gastrointestinal enzymes and thermal process and lead to diarrhea. Enterotoxins are members of superantigens and more than 20 different types have been recognized, however some most important agents include SEA, SEB, SEC, SED and SEE.12,13 On the other hand, increasing antibiotic resistance among coagulase positive staphylococci is an ongoing concern.14 Differentiation of coagulase positive staphylococci except for S. aureus by phenotypic tests is a difficult and unreliable or insufficient process in laboratory settings.15 Considering this, several methods have been introduced for the identification of these strains,16 for example a molecular test including hsp60 and sodA genes could differentiate them.17 S. intermedius is the predominant infectious agent among non-S. aureus coagulase positive species in Iran according to previous reports. The aims

of this study were uncovering the prevalence and clinical importance of coagulase positive staphylococci except for S. aureus with a deep focus on S. intermedius in Iran.

Inclusion and Exclusion Criteria
For this review, words of "Staphylococcus", "zoonotic", "prevalence", "animals", "human" and "Iran" were searched in the internet search engines such as Google Scholar, PubMed, Google, Science Direct and so on.Patients with no history of contact with animals were also included in the study for comparison.Both animal and human coagulase positive isolates were included.Data was analyzed with GraphPad Prism 6, meta-analysis section.

The Burden of Staphylococcus intermedius Infections
Among 20 previously published data, S. intermedius was the most predominant species identified in animal infections in Iran (Figure 1). 1,18Although this species was predominant in several infection sites such as otitis media, the wound infection caused by S. aureus was significantly higher in herds.The hemolytic pattern of staphylococci was in disparity, but higher among coagulase positive than that among coagulase negative species, showing a higher virulence among coagulase positive strains.Other coagulase positive species such as S. hyicus and S. simulans were isolated with lower prevalence, and S. delphini was not detected in the country. 19The prevalence of these species isolated from mastitis infection was significantly higher compared to the normal milk samples.

The Status of Zoonotic Staphylococcal Infections
Staphylococci isolated from animals contain a variety of virulence factors and thus cause a wide range of infections. 20S. intermedius as infectious agent of domestic animals (mostly dogs, cats and pigeons) causes zoonotic infection in a wide range. 21,22It is difficult to identify S. intermedius and S. pseudintermedius using conventional microbiological tests.Molecular diagnostic tools change the understanding of the epidemiology of these 2 organisms. 23The precise identification of these isolates is important in human infections compared to animal infections because they are misdiagnosed instead as S. pseudintermedius with phenotypic tests.In South Africa, isolates of S. intermedius from dog pyoderma were resistant to a few antibiotics including ampicillin and tetracycline.Prevalence of resistance to methicillin was also low. 24. intermedius was not detected in water resources but enterotoxin-producing strains were identified in 8 out of 27 mastitis samples in Brazil.Other enterotoxin-producing staphylococcal species were also mostly identified. 25ata from Iran showed that S. intermedius was the most predominant animal coagulase positive species, infecting human.Other coagulase positive species such as S. hyicus and S. simulans were isolated with lower prevalence, and S. delphini was not detected.The prevalence of these species in mastitis infection was significantly higher compared to the normal milk samples.Other studies from several countries have revealed that S. intermedius and S. pseudintermedius strains are major human infectioncausing agents among coagulase positive staphylococci collected from dogs and cats or in total from animal infections. 26,27These isolates similar to the studies from Iran, have caused a wide variety of infections. 28,29There is a need for identification of S. intermedius which has been demonstrated to produce enterotoxins and also other staphylococcal species from livestock specimens in order to prevent or control their transmission to human. 1,30urther investigations are needed in the country to isolate and characterize S. intermedius, especially enterotoxinproducing and pathogenic strains.

Conclusion
Staphylococcus intermedius was the most predominant isolate identified in animals with the potential of causing infections in humans; however, unlike several studies, the production of enterotoxins was not investigated in the country.Other coagulase positive species such as S. hyicus and S. simulans were isolated with lower prevalence, and S. delphini was not detected.