PhD Doctorate Staphylococci are important opportunistic pathogens often found in the microflora of skin and mucosal surfaces of the upper respiratory tract of man and animals. The coagulase-positive species such as Staphylococcus aureus are capable of causing invasive (eg furuncles and bacteraemia) and non-invasive (food poisoning and toxic shock syndrome) conditions in humans. In animals, S. intermedius and S. aureus have been implicated in a variety of conditions including pyoderma in dogs, mastitis in cows and skin infections in horses with S. intermedius being responsible for more than 95% of staphylococcal infections in dogs. The emergence of antibiotic-resistant bacteria, in humans, animals and the environment, has become a cause for concern following the introduction of antimicrobial agents in clinical practice. Staphylococcal species, in particular, have developed or acquired antibiotic-resistance determinants to almost all the antimicrobial agents in clinical use today. In recent years there has been an increase in reports of the isolation of antibiotic-resistance staphylococci especially methicillin-resistant staphylococci (MRS), from cats and dogs. Cats and dogs are in close contact with humans, especially in advanced countries and therefore the possibility for transfer of antibiotic-resistant staphylococci from these animals to humans or vice versa may exist. The aims of this study were; to determine the species distribution and antibiotic sensitivity of staphylococci obtained from cats and dogs, to investigate the molecular basis of resistance and to examine the genetic relatedness of specific resistant isolates. Many studies have shown that S. intermedius and S. simulans (S. felis) are the predominante species on healthy dogs and cats, respectively, and lesions in these animals are caused by S. aureus and S. intermedius. In this study, a diverse range of coagulase-negative staphylococci was isolated from healthy animals but staphylococci from skin lesions of cats and dogs were identified mainly as S. intermedius as reported in the literature. A limited number of resistant isolates (~20%) were observed in this study and were mostly isolated from dogs. Investigations into the molecular basis of resistance to beta-lactam, macrolide and tetracycline antibiotics were carried out. The resistant isolates were analysed by polymerase chain reaction (PCR) and DNA sequencing techniques. MRS were analysed for the presence of the mecA gene and the staphylococcal cassette chromosome mec (SCCmec). The recombinase genes, cassette chromosome recombinase (ccr) on SCCmec elements were also examined. The SCCmec elements detected were as diverse as those reported in human staphylococcal strains. Comparative analysis of nucleotide and amino acid sequences of mecA and ccr gene complexes revealed that the genes are conserved among MRS of cat and dog orgin. Multilocus sequence typing (MLST) of methicillin-resistant S. aureus (MRSA) and S. epidermidis isolates showed that, the MRSA were of human origin but the S. epidermidis isolates were unique to cats and dogs. In addition, the blaZ gene which codes for ??-lactamases production, the erm genes responsible for erythromycin resistance and the tet genes which encode tetracycline resistances, were found to be identical to those observed in humans and other animal staphylococci and demonstrated similar diversity. The study has provided important information about the molecular basis of resistance in beta-lactamase producing staphylococci as well as the molecular epidemiology of MRS of cat and dog origin and identifies the risk of spread of MRS between humans and pets and vice versa. These findings should form part of a larger surveillance study on staphylococci of cat and dog origin for a better understanding of the epidemiology of antibiotic-resistance genes for improved management and control of resistant staphylococci in the community and in health care settings.