Whole-Genome Sequencing of Staphylococcus haemolyticus Uncovers the Extreme Plasticity of Its Genome and the Evolution of Human-Colonizing Staphylococcal Species

Abstract

Staphylococcus haemolyticus is an opportunistic bacterial pathogen that colonizes human skin and is remarkable for its highly antibiotic-resistant phenotype. We determined the complete genome sequence of S. haemolyticus to better understand its pathogenicity and evolutionary relatedness to the other staphylococcal species. A large proportion of the open reading frames in the genomes of S. haemolyticus, Staphylococcus aureus, and Staphylococcus epidermidis were conserved in their sequence and order on the chromosome. We identified a region of the bacterial chromosome just downstream of the origin of replication that showed little homology among the species but was conserved among strains within a species. This novel region, designated the "oriC environ," likely contributes to the evolution and differentiation of the staphylococcal species, since it was enriched for species-specific nonessential genes that contribute to the biological features of each staphylococcal species. A comparative analysis of the genomes of S. haemolyticus, S. aureus, and S. epidermidis elucidated differences in their biological and genetic characteristics and pathogenic potentials. We identified as many as 82 insertion sequences in the S. haemolyticus chromosome that probably mediated frequent genomic rearrangements, resulting in phenotypic diversification of the strain. Such rearrangements could have brought genomic plasticity to this species and contributed to its acquisition of antibiotic resistance.As a part of the normal bacterial flora, staphylococci colonize the skin and mucosal membranes of humans. In addition, staphylococci frequently cause opportunistic infections in patients with underlying disease, such as those with prosthetic devices, surgical patients, individuals undergoing dialysis, or patients with diabetes. Since antibiotic chemotherapy was introduced in the last century, staphylococci have successfully persisted by altering their genetic traits to avoid being killed. Multidrug-resistant staphylococcal strains, exemplified by methicillin-resistant staphylococci, are now prevalent worldwide. Among 40 staphylococcal species described to date, Staphylococcus aureus is the most virulent species and poses the greatest threat in hospitals worldwide. In addition to its nosocomial spread, S. aureus has also become problematic in community settings, where individuals without predisposing factors have acquired methicillin-resistant staphylococcal infections. Although most community-acquired staphylococcal infections involve the skin and soft tissues, some otherwise healthy children have acquired potentially lethal S. aureus infections with severe symptoms, such as necrotizing pneumonia (5,28,29).To gain a better understanding of the overall pathogenesis of staphylococcal infections and identify novel targets for new chemotherapeutic agents, researchers have sequenced the genomes of seven S. aureus strains (3,9,13,22). A comparative analysis of these strains has revealed that many genes involved in staphylococcal pathogenicity and...

Staphylococcus haemolyticus – an emerging threat in the twilight of the antibiotics age

“…S. aureus versus Staphylococcus epidermidis and Staphylococcus haemolyticus shows *75% average nucleotide identity values, which proves their close genetic relatedness (Konstantinidis et al, 2006;Lamers et al, 2012). That fact is also indicated in the topology of a dendrogram based on the 16S rRNA sequence in Bergey's Manual of Systematic Bacteriology (Vos et al, 2009) as well as in whole-genome sequencing projects comparing different staphylococci strains (Takeuchi et al, 2005) and 134 isolates of S. haemolyticus from geographically diverse origins (Cavanagh et al, 2014).…”

“…Amongst CNS, it was S. haemolyticus that was documented as being resistant to teicoplanin for the first time (Biavasco et al, 2000). It was suggested that S. haemolyticus is unique amongst CNS and especially predisposed to resistance to glycopeptides, because of its extraordinary genome plasticity and tendency to frequent DNA rearrangements (Takeuchi et al, 2005). According to various studies, the percentage of hospital-isolated S. haemolyticus strains with reduced susceptibility to teicoplanin is increasing (Bannerman et al, 1991;Cercenado et al, 1996;Goldstein et al, 1990).…”

“…Apart from the mec gene complex (mecA, mecR1, mecI), they comprise the ccr gene complex encoding chromosomal recombinase, which enables the integration of cassette and chromosomal DNA, and sometimes also other genes encoding virulence factors or associated with resistance to various antimicrobial agents (Hanssen & Ericson Sollid, 2006;Ito et al, 2001). SCCmec cassettes consist of 10-60 kbp (International Working Group on the Classification of In these cases, entire cassette sequencing is often required in order to determine the similarity to those described in the literature (Takeuchi et al, 2005).…”

“…Specificity of the S. haemolyticus genome In 2005, Takeuchi et al (2005) sequenced the entire genome of multiresistant S. haemolyticus strain JCSC1435 consisting of 2685015 bp and three plasmids: 2300, 2366 and 8180 bp. The obtained sequence was compared with the genomes of S. aureus and S. epidermidis reference strains.…”

“…Nowadays, S. aureus, S. epidermidis and S. haemolyticus are the most frequent aetiological agents of staphylococcal infections (Takeuchi et al, 2005). However, their virulence factors differ depending on the species.…”