The Staphylococcus aureus CC398 Lineage: An Evolution Driven by the Acquisition of Prophages and Other Mobile Genetic Elements

Abstract

Among clinically relevant lineages of Staphylococcus aureus, the lineage or clonal complex 398 (CC398) is of particular interest. Strains from this lineage were only described as livestock colonizers until 2007. Progressively, cases of infection were reported in humans in contact with farm animals, and now, CC398 isolates are increasingly identified as the cause of severe infections even in patients without any contact with animals. These observations suggest that CC398 isolates have spread not only in the community but also in the hospital setting. In addition, several recent studies have reported that CC398 strains are evolving towards increased virulence and antibiotic resistance. Identification of the origin and emergence of this clonal complex could probably benefit future large-scale studies that aim to detect sources of contamination and infection. Current evidence indicates that the evolution of CC398 strains towards these phenotypes has been driven by the acquisition of prophages and other mobile genetic elements. In this short review, we summarize the main knowledge of this major lineage of S. aureus that has become predominant in the human clinic worldwide within a single decade.

A review of new emerging livestock-associated methicillin-resistant Staphylococcus aureus from pig farms

“…[ 133 ] reported that approximately 13% of LA-MRSA-positive patients who could not be typed by pulsed-field gel electrophoresis (PFGE) had an active infection compared with 42% of patients with LA-MRSA who could be typed by PFGE, which was less virulent than LA-MRSA. This is consistent with the fact that several virulence determinants have been identified among LA-MRSA CC398 [ 65 , 129 , 136 – 144 ]. However, it is necessary to continuously monitor the determinants and epidemiology of their virulence because several LA-MRSA CC398 isolates have been reported with important human virulence factors, including staphylococcal enterotoxins [ 65 , 139 ] and bicomponent Panton-Valentine leukocidin [ 129 , 137 , 138 , 141 , 142 ].…”

“…This is consistent with the fact that several virulence determinants have been identified among LA-MRSA CC398 [ 65 , 129 , 136 – 144 ]. However, it is necessary to continuously monitor the determinants and epidemiology of their virulence because several LA-MRSA CC398 isolates have been reported with important human virulence factors, including staphylococcal enterotoxins [ 65 , 139 ] and bicomponent Panton-Valentine leukocidin [ 129 , 137 , 138 , 141 , 142 ]. In addition, pig-associated LA-MRSA CC398 was linked with increased MRSA infections in Northern Europe [ 98 ].…”

“…Livestock-associated-methicillin-resistant S. aureus has not yet been associated with food poisoning as LA-MRSA isolates with clonal complex 398 (CC398) rarely carry the enterotoxin gene [ 65 , 66 ]. However, this might change over time because LA-MRSA CC398 can re-acquire the immune evasion gene cluster (IEC), which is present during prophage and is a hallmark of S. aureus infection in humans.…”

Antimicrobial Susceptibility Profiles and Molecular Characterisation of Staphylococcus aureus from Pigs and Workers at Farms and Abattoirs in Zambia

“…However, none of the facilities included in the current study practises such intensive pig rearing. Markedly, MSSA cannot be overlooked as they form the reservoir from which MRSA arise [ 11 , 35 ]. The presence of antimicrobial resistance genes in the present study including tet M, tet K and tet L genes encoding for tetracycline resistance and erm B and erm C genes encoding resistance to erythromycin in some of the isolates indicate the need to closely monitor these strains as they may become a source of antimicrobial resistance given that some of these genes are harboured on plasmids which can be easily transferred between microorganisms [ 36 ].…”

Genomic epidemiology ofS. aureusisolated from bloodstream infections in South America during 2019 supports regional surveillance

“…CC398 was originally described as a livestock-associated lineage, but it is also capable of causing human-to-human transmitted infections as reported from several countries. Phylogenetic evidence later revealed the existence of two distinct CC398 clades (livestock-and human-associated) differing in their repertoire of mobile genetic elements and virulence genes [61][62][63][64][65].…”