Staphylococcus aureus and Staphylococcus pseudintermedius in Animals: Molecular Epidemiology, Antimicrobial Resistance, Virulence and Zoonotic Potential
Staphylococcus aureus is a common colonizer of the skin and mucous of humans and other mammals while dogs are the major host for Staphylococcus pseudintermedius. The epidemiology and ecology of these bacterial species in animals has gained interest in the last years, not only for their importance in veterinary medicine, due to the increment of infectious processes caused by these pathogens (especially by methicillin resistant strains and other antibiotics of interest), but for its increasingly evidenced zoonotic potential. Since 2005, we are facing the spread of livetock-associated methicillin-resistant S. aureus (LA-MRSA) ST398, especially as colonizer of pigs, and the emergence of multidrug resistant methicillin resistant S. pseudintermedius strains (MRSP) in dogs. On the other hand, methicillin-susceptible strains (MSSA and MSSP) play an essential role in the evolution of different genetic lineages. In the first chapter of this thesis, the nasal presence and characterization of S. aureus and S. pseudintermedius strains of dogs, cats and their owners from 43 households were investigated. A total of 42% of owners and 12% of pets were S. aureus carriers. The corresponding rates for S. pseudintermedius were 22.7 and 4.5 for dogs and humans, respectively. Five cases of direct inter-species transmission (same strain on owner and pet) and 5 cases of possible indirect transmission (S. aureus in dogs or S. pseudintermedius in humans) were detected. The carriage dynamics of 7 of these residences along one year was investigated and revealed that dogs are normally transient S. aureus carriers and that dog owners may be persistently colonized by S. pseudintermedius. S. pseudintermedius isolates were more clonally diverse and dynamic in time than S. aureus. Dogs seem to play a relevant role in the staphylococcal species distribution and colonization of in-contact individuals. The detection of several MSSA ST398 from humans with not contact to livestock supports the hypothesis that LAMRSA ST398 may have emerged from humans. In a second chapter, kennel dogs were investigated for the presence and characterization of both bacterial species. High relative MRSP (8%), moderate MSSP (15.3%) and high MSSA (24.5%) nasal carriage rates were revealed. The predominance of multidrug resistant MRSP ST71 among the MRSP lineages detected reflects the success of this clone also in Spain. Distinct phenotypic and genotypic characteristics were revealed among MRSP and MSSP strains. The detection of traditionally human and livestock associated S. aureus suggests the ability of dogs to carry common S. aureus lineages of in-contact environments. MSSA ST398 was the predominant lineage detected, suspecting a more extended host spectrum of this sub-lineage than considered. The comparative analysis of the S. aureus and S. pseudintermedius isolates recovered from household individuals and pound dogs revealed higher levels of antimicrobial resistance and higher virulence gene contend in S. aureus isolates from household individuals. In the third chapter, the presence and characterization of MRSA was investigated in other animal species (pigs at slaughter and hospitalised equines). Half (49%) of tested piglets and 21% of finishing-pigs carried MRSA. High rate of MRSA ST398 (91%) was detected among investigated animals, while a novel ST1379, enclosed within the traditional bovine associated lineage CC97, was detected in 9% of strains. The antimicrobial resistance profile and the clonal distribution of isolates were related to the age of animals investigated. Eight coagulase positive staphylococci from hospitalized equines were additionally characterized. Four strains were multidrug resistant MRSA ST398, revealing its presence in Spain in this animal species. The first detection of a S. pseudintermedius ST68 strain in horses was also reported which, regardless of being multidrug resistant and mecA positive, presented a clear ?-lactams susceptible phenotype. In the final chapter, several human and porcine erm(T) positive LA-MRSA and MSSA ST398 isolates were investigated for the erm(T) genetic environment and location in the genome. Four novel distinct plasmids, all carrying a cadmium resistance operon (cadDX) were detected. A small plasmid, pUR3912, which was also co-located within the chromosomal DNA of the same strain, most probably IS431-mediated, was revealed in MSSA ST398 of human origin. The three other plasmids, from LA-MRSA ST398, carried multiple antimicrobial resistance genes in addition to copper resistance determinants (copA, mco). The physical linkage of antimicrobial resistance genes and genes that confer resistance to heavy metals may facilitate their persistence and dissemination. In addition, the first description of the fexA gene and the transposon Tn558 in S. pseudintermedius is detected. A novel variant (fexAv) that only confers chloramphenicol resistance was revealed and evidenced the presence of 2 punctual substitutions that seem to be implicated in the absence of florfenicol resistance. This thesis studies the population structure of S. aureus and S. pseudintermedius and the dynamics of colonization in different hosts. Direct contact between animals and humans is a relevant factor to take into account to understand the epidemiology and evolution of both bacterial species. Based on the high capacity of both microorganisms to acquire, maintain and (in S. aureus) mobilize antimicrobial resistance genes, further molecular surveillance is warranted to monitor their progress over time.
Gómez Sanz, Elena: Staphylococcus aureus and Staphylococcus pseudintermedius in Animals: Molecular Epidemiology, Antimicrobial Resistance, Virulence and Zoonotic Potential. University of La Rioja, Spain 2013.