Antimicrobial<unk> e is genetically based;<unk> e is mediated by the acquisition of extrachromosomal genetic elements containing genes that confer<unk> e to certain antibiotics. Examples of such elements include plasmids, transposable genetic elements, and genomic islands, which can be transferred between bacteria through horizontal gene transfer. A defining characteristic of<unk>  is its ability to thrive in the presence of penicillin-like antibiotics, which normally prevent bacterial growth by inhibiting synthesis of cell wall material. This is due to a<unk> e gene, mecA, which stops β-lactam antibiotics from inactivating the enzymes (transpeptidases) critical for cell wall synthesis. SCCmec Staphylococcal cassette chromosome mec (SCCmec) is a genomic island of unknown origin containing the antibiotic<unk> e gene mecA. SCCmec contains additional genes beyond mecA, including the cytolysin gene psm-mec, which may suppress virulence in HA-acquired<unk>  strains. In addition, this locus encodes strain-dependent gene regulatory RNAs known as psm-mecRNA. SCCmec also contains ccrA and ccrB; both genes encode recombinases that mediate the site-specific integration and excision of the SCCmec element from the S.<unk>  chromosome. Currently, six unique SCCmec types ranging in size from 21–67 kb have been identified; they are designated types I–VI and are distinguished by variation in mec and ccr gene complexes. Owing to the size of the SCCmec element and the constraints of horizontal gene transfer, a minimum of five clones are thought to be responsible for the spread of<unk>  infections, with clonal complex (CC) 8 most prevalent. SCCmec is thought to have originated in the closely related<unk>  sciuri species and transferred horizontally to S.<unk> . Different SCCmec genotypes confer different microbiological characteristics, such as different antimicrobial<unk> e rates. Different genotypes are also associated with different types of infections. Types I–III SCCmec are large elements that typically contain additional<unk> e genes and are characteristically isolated from HA-MRSA strains. Conversely, CA-MRSA is associated with types IV and V, which are smaller and lack<unk> e genes other than mecA. These distinctions were thoroughly investigated by Collins et al. in 2001, and can be explained by the fitness differences associated with carriage of a large or small SCCmec plasmid. Carriage of large plasmids, such as SCCmecI–III, is costly to the bacteria, resulting in a compensatory decrease in virulence expression.<unk>  is able to thrive in hospital settings with increased antibiotic<unk> e but decreased virulence – HA-MRSA targets immunocompromised, hospitalized hosts, thus a decrease in virulence is not maladaptive. In contrast, CA-MRSA tends to carry lower-fitness cost SCCmec elements to offset the increased virulence and toxicity expression required to infect healthy hosts. mecA mecA is a biomarker gene responsible for<unk> e to<unk>  and other β-lactam antibiotics. After acquisition of mecA, the gene must be integrated and localized in the S.<unk>  chromosome. mecA encodes penicillin-binding protein 2a (PBP2a), which differs from other penicillin-binding proteins as its active site does not bind<unk>  or other β-lactam antibiotics. As such, PBP2a can continue to catalyze the transpeptidation reaction required for peptidoglycan cross-linking, enabling cell wall synthesis even in the presence of antibiotics. As a consequence of the inability of PBP2a to interact with β-lactam moieties, acquisition of mecA confers<unk> e to all β-lactam antibiotics in addition to<unk> . mecA is under the control of two regulatory genes, mecI and mecR1. MecI is usually bound to the mecA promoter and functions as a repressor. In the presence of a β-lactam antibiotic, MecR1 initiates a signal transduction cascade that leads to transcriptional activation of mecA. This is achieved by MecR1-mediated cleavage of MecI, which alleviates MecI repression. mecA is further controlled by two co-repressors, blaI and blaR1. blaI and blaR1 are homologous to mecI and mecR1, respectively, and normally function as regulators of blaZ, which is responsible for penicillin<unk> e. The DNA sequences bound by mecI and blaI are identical; therefore, blaI can also bind the mecA operator to repress transcription of mecA. Arginine catabolic mobile element The arginine catabolic mobile element (ACME) is a virulence factor present in many<unk>  strains but not prevalent in MSSA. SpeG-positive ACME compensates for the polyamine hypersensitivity of S.<unk>  and facilitates stable skin colonization, wound infection, and person-to-person transmission. Strains PBP enzymes, which are essential for cell wall synthesis and thus for bacterial life, by permanently binding to their active sites. Some forms of<unk> , however, express a different PBP that will not allow the antibiotic into its active site. Acquisition of SCCmec in<unk> -sensitive S.<unk>  (MSSA) gives rise to a number of genetically different<unk>  lineages. These genetic variations within different<unk>  strains possibly explain the variability in virulence and associated<unk>  infections. The first<unk>  strain, ST250<unk> -1, originated from SCCmec and ST250-MSSA integration. Historically, major<unk>  clones ST2470-MRSA-I, ST239-MRSA-III, ST5-MRSA-II, and ST5-MRSA-IV were responsible for causing hospital-acquired<unk>  (HA-MRSA) infections. ST239-MRSA-III, known as the Brazilian clone, was highly transmissible compared to others and distributed in Argentina, Czech Republic, and Portugal. In the UK, the most common strains of<unk>  are EMRSA15 and EMRSA16. EMRSA16 has been found to be identical to the ST36:USA200 strain, which circulates in the United States, and to carry the SCCmec type II, enterotoxin A and toxic shock syndrome toxin 1 genes. Under the new international typing system, this strain is now called<unk> 252. EMRSA 15 is also found to be one of the common<unk>  strains in Asia. Other common strains include ST5:USA100 and EMRSA 1. These strains are genetic characteristics of HA-MRSA. Community-acquired<unk>  (CA-MRSA) strains emerged in late 1990 to 2000, infecting healthy people who had not been in contact with healthcare facilities. Researchers suggest that CA-MRSA did not evolve from HA-MRSA. This is further proven by molecular typing of CA-MRSA strains and genome comparison between CA-MRSA and HA-MRSA, which indicate that novel<unk>  strains integrated SCCmec into MSSA separately on its own. By mid-2000, CA-MRSA was introduced into healthcare systems and distinguishing CA-MRSA from HA-MRSA became a difficult process. Community-acquired<unk>  is more easily treated and more virulent than hospital-acquired<unk>  (HA-MRSA). The genetic mechanism for the enhanced virulence in CA-MRSA remains an active area of research. The Panton–Valentine leukocidin (PVL) genes are of particular interest because they are a unique feature of CA-MRSA. In the United States, most cases of CA-MRSA are caused by a CC8 strain designated ST8:USA300, which carries SCCmec type IV, Panton–Valentine leukocidin, PSM-alpha and enterotoxins Q and K, and ST1:USA400. The ST8:USA300 strain results in skin infections, necrotizing fasciitis, and toxic shock syndrome, whereas the ST1:USA400 strain results in necrotizing pneumonia and pulmonary sepsis. Other community-acquired strains of<unk>  are ST8:USA500 and ST59:USA1000. In many nations of the world,<unk>  strains with different genetic background types have come to predominate among CA-MRSA strains; USA300 easily tops the list in the U.S. and is becoming more common in Canada after its first appearance there in 2004. For example, in Australia, ST93 strains are common, while in continental Europe ST80 strains, which carry SCCmec type IV, predominate. In Taiwan, ST59 strains, some of which are<unk>  to many non-beta-lactam antibiotics, have arisen as common causes of skin and soft tissue infections in the community. In a remote region of Alaska, unlike most of the continental U.S., USA300 was found only rarely in a study of<unk>  strains from outbreaks in 1996 and 2000 as well as in surveillance from 2004–06. A<unk>  strain, CC398, is found in intensively reared production animals (primarily pigs, but also cattle and poultry), where it can be transmitted to humans as LA-MRSA (livestock-associated<unk> .
Methicillin-resistant Staphylococcus aureus
Vancomycin-resistant Staphylococcus aureus
Vancomycin-resistant Enterococcus
Streptococcus bovis
Carbapenem-resistant enterobacteriaceae
Streptococcus pyogenes
Staphylococcus haemolyticus
Corynebacterium diphtheriae